VCOG-CTCAE v1.
1 1
Veterinary cooperative oncology
group – common terminology criteria for
adverse events (VCOG-CTCAE) following
chemotherapy or biological antineoplastic
therapy in dogs and cats v1.1
PUBLISH DATE: July, 2011
A consensus document from the veterinary
cooperative oncology group (VCOG)
Quick Reference
The VCOG-CTCAE is a descriptive terminology,
which can be used for Adverse Event (AE) reporting
in dogs and cats. A grading (severity) scale is
provided for each AE term.
Components and Organization
AE and grades apply to both cats and dogs unless
otherwise stated.
Category
A CATEGORY is a broad classification of AEs based
on anatomy and/or pathophysiology. Within each
CATEGORY, AEs are listed accompanied by their
descriptions of severity (Grade).
Adverse Event Terms
An AE is any unfavorable and unintended sign
(including an abnormal clinicopathologic finding),
clinical sign or disease temporally associated with
the use of a medical treatment that may or may not
be considered related to the medical treatment (see
ATTRIBUTION below). An AE is a term that is a
unique representation of a specific event used for
medical documentation and scientific analyses. AEs
are listed alphabetically within CATEGORIES. For
several AEs, a definition is provided and highlighted
in grey within the tables.
© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, DOI: 10.1111/j.1476-5829.2011.00283.x
Grades
Grade refers to the severity of the AE. The VCOG-
CTCAE displays Grades 1 through 5 with unique
clinical description of severity for each AE based on
this general guideline:
Grade 1 Mild; asymptomatic or mild symptoms;
clinical signs or diagnostic observations
only; intervention not indicated.
Grade 2 Moderate; minimal, outpatient or non-
invasive intervention indicated; moder-
ate limitation of activities of daily living
(ADL).
Grade 3 Severe or medically significant but not
immediately life-threatening; hospital-
ization or prolongation of hospitaliza-
tion indicated; disabling; significantly
limiting ADL.
Grade 4 Life-threatening consequences; urgent
interventions indicated.
Grade 5 Death related to AE.
Further Comments
• A semi-colon indicates ‘or’ within the
description of the grade. When items within
the description of the grade are separated
by a comma, the ‘,’ means ‘and’. All items
separated by a comma are necessary to
establish that grade level.
• An ‘ – ’ indicates a grade is not available.
• Not all grades are appropriate for all AEs.
Therefore, some AEs are listed with fewer
than five options for grade selection.
• Grade 5 (Death) is not appropriate for some
AEs and therefore is not an option.
2 VCOG-CTCAE v1.1
Abbreviations Used
• ADL = activities of daily living (eating, sleep-
ing, defecating and urinating)
• AV = atrioventricular
• BSA = body surface area
• CHF = congestive heart failure
• EF = ejection fraction
• EIOP = elevated intraocular pressure
• FS = fractional shortening
• LLN = lower limit of normal
• NSAID = nonsteroidal anti-inflammatory
drug
• PPN = partial parenteral nutrition
• TPN = total parenteral nutrition
• ULN = upper limit of normal
AE Attribution
There exist several potential causes of AEs, including
the protocol intervention under assessment, pre-
existing conditions (e.g. liver disease with associated
liver enzyme abnormalities, diabetes), progression
of disease being treated, concomitant medications
(e.g. steroids) and other causes (e.g. transfusion
reactions, accidental injuries). Documenting and
grading an AE simply reports that an event has
occurred and the seriousness of the event. To be
complete the clinician should assign attribution of
the AE, either to the intervention or something else.
Designating an event as treatment related (or not)
can be done in two ways:
(1) By the treating clinician at the time of clinical
evaluation;
(2) By investigators, usually occurring later in
aggregate data review and reporting by the
investigators.
© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Attribution Standards Are Divided into
Five Categories
(1) Unrelated: The Adverse Event is clearly not
related to the investigational agent(s)
(2) Unlikely: The Adverse Event is doubtfully
related to the investigational agent(s)
(3) Possible: The Adverse Event may be related
to the investigational agent(s)
(4) Probable: The Adverse Event is likely related
to the investigational agent(s)
(5) Definite: The Adverse Event is clearly related
to the investigational agent(s)
TABLE OF CONTENTS:
ADMINISTRATION SITE CONDITIONS . . . . . . 3
ALLERGIC/IMMUNOLOGIC EVENT . . . . . . . . . 4
BLOOD/BONE MARROW . . . . . . . . . . . . . . . . . . . . 5
CARDIAC ARRHYTHMIA . . . . . . . . . . . . . . . . . . . . 6
CARDIAC GENERAL . . . . . . . . . . . . . . . . . . . . . . . . 7
COAGULATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
CONSTITUTIONAL CLINICAL SIGNS . . . . . . . . 8
DERMATOLOGIC/SKIN . . . . . . . . . . . . . . . . . . . . . 9
EAR AND LABYRINTH DISORDERS . . . . . . . . . 11
ENDOCRINE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
GASTROINTESTINAL . . . . . . . . . . . . . . . . . . . . . . 13
HAEMORRHAGE/BLEEDING . . . . . . . . . . . . . . . 15
HEPATOBILIARY/PANCREAS . . . . . . . . . . . . . . . 16
METABOLIC/LABORATORY . . . . . . . . . . . . . . . . 17
MUSCULOSKELETAL/SOFT TISSUE . . . . . . . . . 19
NEUROLOGY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
OCULAR/VISUAL . . . . . . . . . . . . . . . . . . . . . . . . . . 22
PAIN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
PULMONARY/RESPIRATORY . . . . . . . . . . . . . . 24
RENAL/GENITOURINARY . . . . . . . . . . . . . . . . . . 26
NEOPLASMS BENIGN, MALIGNANT AND
UNSPECIFIED (INCL CYSTS AND POLYPS) . 28
SEXUAL/REPRODUCTIVE FUNCTION . . . . . . 29
VASCULAR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
 ADMINISTRATION SITE CONDITIONS

Grade
Adverse Event 1 2 3 4 5

Infusion-related reaction Mild transient reaction; Infusion interruption indicated but Prolonged (e.g. not rapidly responsive Life-threatening consequences; Death
infusion interruption not responds promptly to medical to medication and/or brief urgent intervention indicated
indicated; intervention not treatment (e.g. antihistamines, NSAIDs, interruption of infusion); recurrence
indicated narcotics, IV fluids); prophylactic of signs following initial
medications indicated for ≤24 h improvement; hospitalization
indicated for clinical sequelae
Definition: A disorder characterized by adverse reaction to the infusion of pharmacological or biological substances.
Infusion site — Erythema with associated signs (e.g. Ulceration or necrosis; severe tissue Life-threatening consequences; Death
extravasation oedema, pain, induration, phlebitis) damage; operative intervention urgent intervention indicated
indicated
Definition: A disorder characterized by leakage of a pharmacological or a biological substance from the infusion site into the surrounding tissue. Signs include induration, erythema, swelling and
marked discomfort at the infusion site.
Injection site reaction Tenderness with or without Pain; lipodystrophy; oedema; phlebitis Ulceration or necrosis; severe tissue Life-threatening consequences; Death
associated signs (e.g. damage; operative intervention urgent intervention indicated
warmth, erythema, itching) indicated
Definition: A disorder characterized by an intense adverse reaction (usually immunological) developing at the site of an injection.
Other (Specify, ) Mild Moderate Severe Life-threatening; disabling Death
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ALLERGIC/IMMUNOLOGIC EVENT

Grade
Adverse Event 1 2 3 4 5

Allergic reaction/ Transient urticaria or rash, drug Intervention or infusion interruption Prolonged (e.g. not rapidly responsive to Life-threatening consequences; Death
VCOG-CTCAE v1.1

hypersensitivity fever <40 ◦ C (<104 ◦ F); indicated; responds promptly to medication and/or brief interruption urgent intervention indicated
intervention not indicated treatment (e.g. antihistamines, of infusion); recurrence of signs
NSAIDs, narcotics); prophylactic following initial improvement;
medications indicated for ≤24 h hospitalization indicated for clinical
sequelae (e.g. renal impairment,
pulmonary infiltrates or oedema)
Definition: A disorder characterized by an adverse local or general response from exposure to an allergen.
Anaphylaxis — — Bronchospasm, with or without Life-threatening consequences; Death
urticaria; parenteral intervention urgent intervention indicated
indicated; allergy-related oedema/
angiooedema; hypotension
Definition: A disorder characterized by an acute inflammatory reaction resulting from the release of histamine and histamine-like substances from mast cells, causing a hypersensitivity immune
response. Clinically, it presents with breathing difficulty, hypotension, cyanosis and loss of consciousness and may lead to death.
Autoimmune disorder Subclinical and serologic or other Evidence of autoimmune reaction Reversible reaction involving function of Autoimmune reaction with Death
evidence of autoimmune involving a nonessential organ or a major organ or other adverse event life-threatening
reaction, with normal organ function (e.g. hypothyroidism) (e.g. transient colitis or anaemia) consequences
function and intervention not
indicated
Definition: A disorder resulting from loss of function or tissue destruction of an organ or multiple organs, arising from humoral or cellular immune responses of the individual to their own tissue
constituents.
Serum sickness Clinical or diagnostic observations Moderate arthralgia; fever, rash, Severe arthralgia or arthritis; extensive Life-threatening consequences; Death
only; intervention not indicated urticaria, antihistamines indicated rash; steroids or IV fluids indicated pressor or ventilatory support
indicated
Definition: A disorder characterized by a delayed-type hypersensitivity reaction to foreign proteins derived from an animal serum. It occurs approximately six to twenty-one days following the
administration of the foreign antigen. Signs include fever, arthralgias, myalgias, skin eruptions, lymphadenopathy, and dyspneoa.

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Vasculitis (Not Mild, intervention not indicated Nonsteroidal medical intervention Steroids indicated Ischaemic changes; amputation Death
including indicated or surgical debridement
perivascular injection indicated
of drug)
Definition: A disorder characterized by inflammation involving the wall of a vessel.
Other (Specify, ) Mild Moderate Severe Life-threatening; disabling Death
 BLOOD/BONE MARROW

Grade
Adverse Event 1 2 3 4 5

Bone marrow Mildly hypocellular; <25% reduction Moderately hypocellular; >25 to Severely hypocellular; >50% — Death
cellularity from normal cellularity for age <50% reduction from normal reduction from normal cellularity
cellularity for age for age
Definition: A disorder characterized by the inability of the bone marrow to produce haematopoietic elements.
Haemoglobin Dog: Dog: Dog: Dog: Death
10 g dL−1 to <LLN <10–8.0 g dL−1 <8.0–6.5 g dL−1 <6.5 g dL−1
Cat: Cat: Cat: Cat:
8.0 g dL−1 to <LLN <8.0–6.5 g dL−1 <6.5–5.0 <5.0
Haemolysis Laboratory evidence of haemolysis Evidence of haemolysis and ≥2 g Transfusion or medical intervention Life-threatening consequences; Death
only (e.g. direct antiglobulin test; decrease in haemoglobin. indicated (e.g. steroids) urgent intervention indicated
DAT; Coombs’ test; schistocytes
Definition: A disorder characterized by laboratory test results that indicate widespread erythrocyte cell membrane destruction.
Packed cell volume Dog: Dog: Dog: Dog: Death
30% to <LLN 20 to <30% 15 to <20% <15%
Cat: Cat: Cat: Cat:
25% to <LLN 20 to <25% 15 to <20% <15%
Neutropenia 1500 μL−1 to <LLN 1000–1499 μL−1 500–999 μL−1 <500 μL−1 Death
Neutrophilia — 50 000–100 000 μL−1 >100 000 μL−1 Clinical manifestations of leucostasis; —
urgent intervention indicated
Thrombocytopenia 100 000 μL−1 to <LLN 50 000–99 000 μL−1 25 000–49 000 μL−1 <25 000 Death
Other Mild Moderate Severe Life-threatening; disabling Death
(Specify, )
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CARDIAC ARRHYTHMIA

Grade
Adverse Event 1 2 3 4 5

Conduction abnormality/atrioventricular Asymptomatic, intervention Non-urgent medical Incompletely controlled medically Life-threatening (e.g. arrhythmia Death
VCOG-CTCAE v1.1

heart block. Select: not indicated intervention indicated or controlled with device (e.g. associated with CHF,
-Asystole pacemaker) hypotension, syncope, shock)
-AV block – first degree
-AV block – second degree Mobitz I
-AV block – second degree Mobitz II
-AV block – third degree (complete)
-Sick sinus syndromes
-Other (specify)

Supraventricular and nodal arrhythmia. Asymptomatic, intervention Non-urgent medical Symptomatic and incompletely Life-threatening (e.g. arrhythmia Death
Select: not indicated intervention indicated controlled medically or associated with CHF,
-Atrial fibrillation controlled with device (e.g. hypotension, syncope, shock)
-Atrial flutter pacemaker)
-Atrial tachycardia/paroxysmal
-Atrial tachycardia
-Nodal/junctional
-Sinus tachycardia
-Supraventricular extrasystoles
-Supraventricular tachycardia
-Other (Specify, )

Ventricular arrhythmia. Select: Asymptomatic, intervention Non-urgent medical Symptomatic and incompletely Life-threatening (e.g. arrhythmia Death
-Bigeminy not indicated intervention indicated controlled medically or associated with CHF,
-Idioventricular rhythm controlled with device (e.g. hypotension, syncope, shock)
-Premature ventricular contractions pacemaker)

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
-Torsade de pointes
-Trigeminy
-Ventricular fibrillation
-Ventricular flutter
-Ventricular tachycardia
-Other (Specify, )

Other Cardiac Arrhythmia Mild Moderate Severe Life-threatening; disabling Death

(Specify, )
 CARDIAC GENERAL

Grade
Adverse Event 1 2 3 4 5

Bradycardia <60 bpm <40 bpm <30 bpm <20 bpm Death
Cardiopulmonary — — — Life-threatening Death
arrest
Hypertension Asymptomatic, transient (<24 h) Recurrent or persistent (>24 h) or Requiring more than one drug or Life-threatening consequences (e.g. Death
increase, intervention not clinical signs increase; monotherapy more intensive therapy hypertensive crisis)
indicated may be indicated
Hypotension Asymptomatic, transient (<24 h), Brief (<24 h) fluid replacement or Sustained (>24 h) therapy, resolves Shock (e.g. impairment of vital organ Death
intervention not indicated other therapy; no physiological without persisting physiological function)
consequences consequences
Left ventricular Asymptomatic diagnostic finding Asymptomatic, Intervention indicated Symptomatic CHF responsive to Refractory CHF, poorly controlled with Death
diastolic without associated signs; intervention intervention
dysfunction intervention not indicated
Left ventricular Asymptomatic, resting ejection Asymptomatic, resting EF <50–40%; Symptomatic CHF responsive to Refractory CHF or poorly controlled; Death
systolic fraction (EF) <60–50%; fractional FS 15–20% intervention; EF < 40–20%, EF< 20%
dysfunction shortening (FS) 20–25% FS < 15%
Myocarditis — — CHF responsive to intervention Severe or refractory CHF Death
Pericardial effusion — Effusion without associated clinical Physiological consequences Life-threatening; emergency Death
(non-malignant) signs intervention indicated
Right ventricular No associated clinical signs without Absence of associated clinical signs, Cor pulmonale present, responsive to Cor pulmonale, poorly controlled Death
dysfunction (cor therapy however therapy indicated intervention
pulmonale)
Valvular heart Valvular thickening with or without Moderate regurgitation or stenosis by Severe regurgitation or stenosis; signs Life-threatening; disabling; poorly Death
disease mild valvular regurgitation or imaging controlled with medical therapy responsive to medical therapy
stenosis, treatment not indicated
Other Mild Moderate Severe Life-threatening; disabling Death
(Specify, )
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COAGULATION

Grade
Adverse Event 1 2 3 4 5

Disseminated intravascular — Laboratory findings, no Laboratory findings, evidence of Laboratory findings, life-threatening or disabling consequences (e.g. Death
coagulation haemorrhage detected haemorrhage, non-disabling CNS haemorrhage, organ damage or haemodynamically
VCOG-CTCAE v1.1

significant blood loss)

Definition: A disorder characterized by systemic pathological activation of blood clotting mechanisms which results in clot formation throughout the body. There is an increase in the risk of
haemorrhage as the body is depleted of platelets and coagulation factors.
Prothrombin time >1–1.9× ULN >2.0–2.9× ULN >3× ULN Grades 2–3, Life-threatening bleeding —
Partial thromboplastin time >1–1.9× ULN >2.0–2.9× ULN >3× ULN Grades 2–3, Life-threatening bleeding —
Other (Specify, ) Mild Moderate Severe Life-threatening; disabling Death

CONSTITUTIONAL CLINICAL SIGNS

Grade
Adverse Event 1 2 3 4 5

Lethargy/fatigue/ Mild lethargy over baseline; Moderate lethargy causing some difficulty Compromised, severely restricted in Disabled, must be force fed and Death
general diminished activity from with performing ADL; ambulatory only to ADL; unable to confine urinations helped to perform ADL
performance predisease level, but able to the point of eating, sleeping and and defecation to acceptable
function as an acceptable pet consistently defecating and urinating in areas; will consume food if offered
acceptable areas in place
Definition: Disorders characterized by a state of generalized weakness with a pronounced inability to summon sufficient energy to accomplish daily activities.
Fever 39.5–40.0 ◦ C >40.0–41 ◦ C >41–42 ◦ C >42◦ Death
(103.5–104 ◦ F) (>104–105.8 ◦ F), transient (<6 h), not (>105.8–107.6 ◦ F), prolonged (>107.6 ◦ F)
requiring hospitalization (>6 h); requiring hospitalization
Hypothermia — 36 to >33 ◦ C 33 to >28 ◦ C <28 ◦ C Death
◦ ◦

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
(96.8 to >91.4 F) (91.4 to >82.4 F) (<82.4 ◦ F)
or life-threatening consequences
(e.g. coma, hypotension,
pulmonary oedema)
Weight loss <10% from baseline; 10–15% from baseline; nutritional dietary >15% of baseline — Death
intervention not indicated modification indicated
Other Mild Moderate Severe Life-threatening; disabling Death
(Specify, )
 DERMATOLOGIC/SKIN

Grade
Adverse Event 1 2 3 4 5

Alopecia Sparse thinning or denuding of hair at Generalized thinning of hair coat, — — —

localized site, patchy alopecia generalized alopecia
Definition: A disorder characterized by a decrease in density of hair compared to normal for a given individual at a given age and body location.
Bruising (in the absence Localized or in a dependent area Generalized. — — —
of grade 3 or 4
thrombocytopenia)
Definition: A finding of injury of the soft tissues or bone characterized by leakage of blood into surrounding tissues.
Erythema Limited to localized site Generalized — — —
Definition: Superficial reddening of the skin, usually in patches, as a result of injury or irritation causing dilatation of the blood capillaries.
Erythema multiforme Target lesions covering <10% BSA and Target lesions covering 10–30% BSA and Target lesions covering >30% BSA and Target lesions covering >30% BSA; Death
not associated with skin tenderness associated with skin tenderness associated with oral or genital erosions associated with fluid or
electrolyte abnormalities; ICU
care indicated
Definition: A disorder characterized by target lesions (a pink–red ring around a pale centre).
Hyperpigmentation Slight or localized Marked or generalized — — —
Hypopigmentation Slight or localized Marked or generalized — — —
Nail/claw changes Discolouration, pitting Weakening Partial or complete loss of nail(s)/claw(s); Significantly interfering with —
pain ADL – unwilling to ambulate
Palmar–plantar Minimal changes or dermatitis (e.g. Skin changes (e.g. peeling, blisters, Ulcerative dermatitis or skin changes with — —
erythrodysesthesia erythema) without pain bleeding, oedema) or pain, not pain interfering with function
syndrome interfering with function, easily
managed medically
Definition: A disorder characterized by redness, marked discomfort, swelling, and possible ulceration of the palmar/plantar surfaces of the paws.
Photosensitivity Painless erythema Painful erythema Erythema with desquamation Life-threatening; disabling Death
Definition: A disorder characterized by an increase in sensitivity of the skin to light.
Pruritus Mild or localized Moderate or widespread and occurs Severe and prolonged; continues when — —
regularly; may occur at night but not eating, playing, exercising, limits
when eating or playing sleeping; oral corticosteroid or
immunosuppressive therapy indicated
Definition: A disorder characterized by intense itching.
Purpura Combined area of lesions covering <10% Combined area of lesions covering Combined area of lesions covering >30% — —
BSA 10–30% BSA; bleeding with trauma BSA; spontaneous bleeding
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 DERMATOLOGIC/SKIN (CONTINUED)

Grade
Adverse Event 1 2 3 4 5
Definition: A disorder characterized by haemorrhagic areas of the skin and mucous membrane. Newer lesions appear reddish in colour. Older lesions are usually darker purple in colour and eventually become
brownish-yellow in colour.
Rash: acne/ Papules and/or pustules covering Papules and/or pustules covering Papules and/or pustules covering Papules and/or pustules covering any % BSA, Death
10 VCOG-CTCAE v1.1

acneiform <10% BSA, which may or may not 10–30% BSA, which may or may not >30% BSA, which may or may not be which may or may not be associated with
be associated with symptoms of be associated with symptoms of associated with symptoms of symptoms of pruritus or tenderness and are
pruritus or tenderness pruritus or tenderness pruritus or tenderness; limiting ADL; associated with extensive superinfection
associated with local superinfection with IV antibiotics indicated; life-threatening
with oral antibiotics indicated consequences
Definition: A disorder characterized by an eruption of papules and pustules.
Rash: maculo-papula Macules/papules covering <10% Macules/papules covering 10–30% Macules/papules covering >30% BSA — —
BSA with or without BSA with or without symptoms (e.g. with or without
symptoms (e.g. pruritus) pruritus); associated symptoms
Definition: A disorder characterized by the presence of macules (flat) and papules (elevated). Also known as morbilliform rash.
Scaling Fine scaling, noticeable only upon Scaling easily visible but not exfoliation Easily visible generalized scaling and — —
close examination in clumps; minimal crusting crusting with generalized exfoliation
upon examination
Definition: A disorder characterized by flaky and dull skin.
Skin atrophy Covering <10% BSA; associated with Covering 10–30% BSA; associated with Covering >30% BSA; associated with — —
telangiectasia or changes in skin striae or adnexal structure loss ulceration
colour
Definition: A disorder characterized by the degeneration and thinning of the epidermis and dermis.
Skin ulceration Combined area of ulcers <1 cm; Combined area of ulcers 1–2 cm; Combined area of ulcers >2 cm; Any size ulcer with extensive destruction, tissue Death
nonblanchable erythema of intact partial thickness skin loss involving full-thickness skin loss involving necrosis or damage to muscle, bone or
skin with associated warmth or skin or subcutaneous fat damage to or necrosis of supporting structures with or without
oedema subcutaneous tissue that may full-thickness skin loss
extend down to fascia
Definition: A disorder characterized by circumscribed, inflammatory and necrotic erosive lesion on the skin.
Toxic epidermal — — — Skin sloughing covering ≥30% BSA with Death

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
necrolysis associated symptoms (e.g. erythema,
purpura or epidermal
detachment)
Definition: A disorder characterized by greater than 30% total body skin area separation of dermis. The syndrome is thought to be a hypersensitivity complex affecting the skin and the mucous membranes.
Urticaria (hives, welts, — Transient, intervention indicated <48 h Intervention indicated >48 h — —
wheals)
Definition: A disorder characterized by a pruritic skin eruption characterized by wheals with pale interiors and well-defined red margins.
Other Mild Moderate Severe Life-threatening; disabling Death
(Specify, )
 EAR AND LABYRINTH DISORDERS

Grade
Adverse Event 1 2 3 4 5

Ear pain Mild pain Moderate pain; not limiting ADL Severe pain; limiting ADL — —
Definition: A disorder characterized by a sensation of marked discomfort in the ear.
External ear External otitis with erythema or External otitis with moist External otitis with mastoiditis; Urgent operative intervention indicated Death
inflammation dry desquamation desquamation, oedema, stenosis or osteomyelitis; necrosis
enhanced cerumen or discharge; of soft tissue or bone
tympanic membrane perforation;
tympanostomy
Definition: A disorder characterized by inflammation, swelling and redness to the outer ear and ear canal.
External ear pain Mild pain Moderate pain; not limiting ADL Severe pain; limiting ADL — —
Definition: A disorder characterized by a sensation of marked discomfort in the external ear region.
Hearing impaired Slow to respond to auditory Only responsive to loud auditory Clinically deaf; severe BAER — —
stimuli; mild BAER abnormalities stimuli; moderate BAER abnormalities
abnormalities
Definition: A disorder characterized by partial or complete loss of the ability to detect or understand sounds resulting from damage to ear structures. BAER = brainstem auditory evoked potentials.
Middle ear Serous otitis Serous otitis, medical intervention Mastoiditis; necrosis of canal soft Life-threatening consequences; urgent Death
inflammation indicated tissue or bone intervention indicated
Definition: A disorder characterized by inflammation, swelling and redness to the middle ear.
Vertigo — Symptomatic; not limiting ADL Severe symptoms; limiting ADL — —
Definition: A disorder characterized by dizziness, imbalance, nausea, and vision problems.
Other Mild Moderate Severe Life-threatening; disabling Death
(Specify, )
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 ENDOCRINE

Grade
Adverse Event 1 2 3 4 5
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Adrenal Asymptomatic, intervention not Symptomatic, intervention indicated Hospitalization Life-threatening; disabling Death
insufficiency indicated
Definition: A disorder that occurs when the adrenal cortex does not produce enough of the hormone cortisol and in some cases, the hormone aldosterone. It may be due to a disorder of the adrenal
cortex as in Addison’s disease or primary adrenal insufficiency.
Pancreatic Asymptomatic, intervention not Symptomatic, dietary modification or Symptoms interfering with ADL; Life-threatening consequences (e.g. Death
endocrine: indicated oral agent indicated insulin indicated ketoacidosis, hyperosmolarity)
glucose
intolerance
Definition: A disorder characterized by insufficient production of pancreatic insulin leading to glucose intolerance.
Pancreatic exocrine: Asymptomatic, intervention not Symptomatic, dietary modification or Symptoms interfering with ADL; grade Life-threatening consequences; Death
maldigestion indicated oral agents indicated 3 weight loss cachexia
Definition: A disorder characterized by insufficient production of pancreatic exocrine enzymes leading to maldigestion.
Parathyroid Asymptomatic, intervention not Symptomatic, intervention indicated — — Death
function (hyper- indicated
parathyroidism)
Definition: A disorder characterized by an increase in production of parathyroid hormone by the parathyroid glands. This results in hypercalcaemia.
Parathyroid Asymptomatic; clinical or diagnostic Moderate symptoms; medical Severe symptoms; medical Life-threatening consequences; Death
function observations only; intervention not intervention indicated intervention and hospitalization urgent
(hypoparathy- indicated indicated intervention indicated
roidism)
Definition: A disorder characterized by a decrease in the production of parathyroid hormone by the parathyroid glands.
Thyroid function, Asymptomatic; clinical or diagnostic Symptomatic; thyroid suppression Severe symptoms; limiting ADL, Life-threatening consequences; Death
hyperthyroidism observations only; intervention not therapy indicated; limiting ADL hospitalization indicated urgent intervention indicated
indicated
Definition: A disorder characterized by excessive levels of thyroid hormone in the body. Common causes include an overactive thyroid gland or thyroid hormone overdose.

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Thyroid function, Asymptomatic, intervention not Symptomatic, not interfering with Symptoms interfering with ADL, Life-threatening myxoedema; coma Death
hypothyroidism indicated ADL, thyroid replacement indicated hospitalization indicated
Definition: A disorder characterized by a decrease in production of thyroid hormone by the thyroid gland.
Other Mild Moderate Severe Life-threatening; disabling Death
(Specify, )
 GASTROINTESTINAL

Grade
Adverse Event 1 2 3 4 5

Abdominal Clinical or diagnostic observations only; Clinical signs present; outpatient medical Severe discomfort; limiting ADL; inpatient — —
distention intervention not indicated management indicated management indicated
Definition: A disorder characterized by swelling of the abdomen.
Anorexia Coaxing or dietary change required to Oral intake altered (≤3 days) without Of >3 days duration; associated with Life-threatening consequences; Death
maintain appetite significant weight loss; oral nutritional significant weight loss (≥10%) or TPN indicated; >5 days
supplements/appetite stimulants may malnutrition; IV fluids, tube feeding or duration
be indicated force feeding indicated
Definition: A disorder characterized by a loss of appetite.
Ascites Clinical or diagnostic observations only; Symptomatic; medical intervention Severe symptoms; invasive intervention Life-threatening consequences; Death
intervention not indicated indicated indicated urgent operative intervention
indicated
Definition: A disorder characterized by accumulation of serous or haemorrhagic fluid in the peritoneal cavity
Colitis Asymptomatic, pathological or Abdominal cramping/pain; mucus or Abdominal pain, fever, change in bowel Life-threatening consequences Death
radiological findings only blood in stool; outpatient medical habits, ileus, peritoneal signs; (e.g. perforation, bleeding,
intervention indicated; ≤5 days hospitalization indicated; >5 days ischaemia, necrosis)
duration duration
Definition: A disorder characterized by inflammation of the colon.
Constipation Occasional or intermittent symptoms; Persistent symptoms with regular use of Symptoms interfering with ADL; Life-threatening consequences Death
occasional use of stool softeners, laxatives or enemas indicated obstipation with manual evacuation (e.g. obstruction, megacolon)
laxatives, dietary modification or indicated
enema
Definition: A disorder characterized by irregular and infrequent or difficult evacuation of the bowels.
Dehydration Increased oral fluids indicated; dry Parenteral (IV or SC) fluids indicated IV fluids indicated >48 h Life-threatening (e.g. Death
mucous membranes; <skin turgor <48 h haemodynamic collapse)
Definition: A disorder characterized by excessive loss of water from the body. It is usually caused by severe diarrhoea.
Diarrhoea Increase of up to 2 stools per day over Increase of 3–6 stools per day over Increase of >6 stools per day over Life-threatening (e.g. Death
baseline; no increase in frequency, baseline; medications indicated; baseline; incontinence >48 h; IV fluids haemodynamic collapse)
however, consistency decreased over parenteral (IV or SC) fluids indicated >48 h; hospitalization; interfering with
baseline ≤48 h; not interfering with ADL ADL
Definition: A disorder characterized by frequent and watery bowel movements.
Dysphagia Symptomatic but able to eat regular diet Symptomatic and altered Symptomatic and severely altered Life-threatening (e.g. Death
eating/swallowing (e.g. altered dietary eating/swallowing (e.g. inadequate oral obstruction, perforation)
VCOG-CTCAE v1.1

habits, food consistency); parenteral (IV caloric or fluid intake); IV fluids >48 h,
or SC) fluids indicated <48 h tube feeding or PPN/TPN indicated
13

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
 GASTROINTESTINAL (CONTINUED)

Grade
Adverse Event 1 2 3 4 5
Definition: A disorder characterized by difficulty in swallowing.
Enteritis Asymptomatic, pathological or Abdominal pain/cramping; mucus or Abdominal pain/cramping, fever, Life-threatening (e.g. Death
14 VCOG-CTCAE v1.1

radiological findings only blood in stool); medical management change in bowel habits with ileus; perforation, bleeding,
indicated; hospitalization ≤48 h peritoneal signs; hospitalization ischaemia, necrosis)
indicated >48 h indicated
Definition: A disorder characterized by inflammation of the small intestine.
Flatulence Mild Moderate — — —
Definition: A disorder characterized by a state of excessive gas in the intestinal tract.
Gastric ulceration Clinical or diagnostic observations only; Altered GI function; medical intervention Severely altered GI function; TPN Life-threatening Death
intervention not indicated indicated indicated; elective consequences; urgent
operative or endoscopic operative intervention
intervention indicated indicated; gastric
perforation
Definition: A disorder characterized by a circumscribed, inflammatory and necrotic erosive lesion on the mucosal surface of the stomach.
Ileus, GI Asymptomatic, radiological finding only Symptomatic; altered GI function (e.g. Symptomatic and severely altered GI Life-threatening Death
altered dietary habits); parenteral (IV or function; IV fluids, tube feedings or consequences
SC) fluids indicated ≤48 h PPN/TPN indicated >48 h
Definition: A disorder characterized by failure of the ileum to transport intestinal contents.
Incontinence, anal Occasional Daily Interfering with ADL; operative Permanent Death
intervention indicated
Definition: A disorder characterized by inability to consciously control rectal evacuation.
Mucositis/ Erythema of the mucosa Patchy ulcerations or pseudomembranes Confluent ulcerations or Tissue necrosis; significant Death
stomatitis pseudomembranes; bleeding with spontaneous bleeding;
minor trauma life-threatening
Definition: A disorder characterized by inflammation of the oral mucosa.
Nausea/ptyalism Loss of appetite without alteration in Salivation or ‘smacking of lips’ <3 days, Salivation or ‘smacking of lips’ Salivation or ‘smacking of lips’ —

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
eating habits grade 2 anorexia >3–5 days, grade 3 anorexia >5 days, grade 4 anorexia
Definition: A disorder characterized by hypersalivation and sensation or urge to vomit – difficult to assess in companion species.
Vomiting <3 episode in 24 h, medical 3–10 episodes in 24 h; <5 episodes/day Multiple episodes >48 h and IV fluids Life-threatening (e.g. Death
intervention not indicated for ≤48 h; parenteral fluids (IV or SC) or PPN/TPN indicated >48 h haemodynamic collapse)
indicated ≤48 h; medications indicated
Definition: A disorder characterized by the reflexive act of ejecting the contents of the stomach through the mouth.
Other Mild Moderate Severe Life-threatening Death
(Specify, )
 HAEMORRHAGE/BLEEDING

Grade
Adverse Event 1 2 3 4 5

Haematoma Minimal signs, invasive intervention Minimally invasive evacuation or Transfusion or operative intervention Life-threatening; major urgent Death
not indicated aspiration indicated indicated intervention indicated
Definition: A disorder characterized by a localized collection of blood, usually clotted, in an organ, space or tissue, due to a break in the wall of a blood vessel.
Haemorrhage/bleeding — — Requiring transfusion(s) beyond what is Life-threatening Death
associated with surgery, ‘normal’ for that procedure; operative
intraoperative or intervention
postoperative
Definition: Bleeding associated with an operative procedure
Haemorrhage/bleeding, Mild or microscopic, intervention not Symptomatic, medical or minor Transfusion, operative intervention Life-threatening; major urgent Death
spontaneous indicated operative intervention indicated indicated intervention indicated
Specify site:
Definition: Bleeding occurring spontaneously, without a history of trauma or operative procedure
Petechiae/ecchymoses Few petechiae Moderate petechiae; ecchymoses Generalized petechiae or ecchymoses — Death
(skin or mucosa)
Definition: small or patchy red or purple spot caused by bleeding into the skin.
Other (Specify, ) Mild Moderate Severe Life-threatening; disabling Death
VCOG-CTCAE v1.1
15

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
 16 VCOG-CTCAE v1.1

HEPATOBILIARY/PANCREAS

Grade
Adverse Event 1 2 3 4 5

Cholecystitis Asymptomatic, radiologic Symptomatic, medical Operative or endoscopic intervention Life-threatening (e.g. sepsis or Death
findings only intervention indicated required perforation)
Definition: A disorder characterized by inflammation involving the gallbladder. It may be associated with the presence of gallstones.
Liver — — Jaundice Encephalopathy or coma Death
dysfunction/failure
Definition: A disorder characterized by the inability of the liver to metabolize chemicals in the body. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase
and alkaline phosphatase.
Pancreatic exocrine — Increase in stool frequency, bulk or Sequelae of absorption deficiency (e.g. Life-threatening Death
insufficiency odour; steatorrhoea weight loss)
Definition: A disorder characterized by insufficient production of pancreatic exocrine enzymes leading to maldigestion.
Pancreatitis Enzyme elevation; radiological Grade 1 or 2 vomiting; medical Severe pain; grade 3 or higher vomiting; Life-threatening consequences; Death
findings only intervention indicated plasma or other transfusion necessary urgent intervention indicated
(e.g. analgesia, parenteral
hydration, nutritional support)
Definition: A disorder characterized by inflammation of the pancreas.
Other (Specify, ) Mild Moderate Severe Life-threatening; disabling Death

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
 METABOLIC/LABORATORY

Grade
Adverse Event 1 2 3 4 5

Acidosis pH< normal, but ≥7.3 — pH <7.3 Life-threatening consequences Death

Albumin, low <LLN–2.0 g dL−1 <2.0–1.5 g dL−1 <1.5 g dL−1 — —
Alkaline Dog: Dog: Dog: Dog: —
phosphatase >ULN to 2.5× ULN >2.5–5.0 × ULN, transient >5.0–20× ULN >20× ULN
Cat: (<2 weeks) Cat: Cat:
>ULN to 1.25× ULN Cat: >1.5–2.0× ULN >2× ULN
>1.25–1.5 × ULN, transient
(<2 weeks)
Alkalosis pH > normal, but ≤7.5 — pH > 7.5 Life-threatening consequences Death

ALT Dog: Dog: Dog: Dog: —

>ULN to 1.5× ULN >1.5–4.0× ULN, transient >4.0–10× ULN >10× ULN
Cat: (<2 weeks) Cat: Cat:
>ULN to 1.25× ULN Cat: >1.5–2.0× ULN >2× ULN
>1.25–1.5× ULN, transient
(<2 weeks)
Amylase >ULN to 1.5× ULN >1.5–2.0× ULN >2.0–5× ULN >5× ULN —
AST >ULN to 1.5× ULN >1.5–2.0× ULN >2.0–10× ULN >10× ULN —
Bile acids
Bilirubin >ULN to 1.5× ULN >1.5–3.0× ULN >3.0–10× ULN >10× ULN —
BUN >1–1.5× baseline; >1.5–3× baseline; >3× baseline; >2.0–3× ULN >3× ULN —
>ULN to 1.5× ULN >1.5–2.0× ULN
Calcium, low <LLN–8.0 mg dL−1 <8.0–7.0 mg dL−1 <7.0–6.0 mg dL−1 <6.0 mg dL−1 Death
Ionized dog: <LLN–1.1 nmol Ionized dog: <1.1–1.0 nmol L−1 Ionized dog: <1.0–0.9 nmol L−1 Ionized dog: <0.9 nmol L−1
L−1 Ionized cat: <0.9–0.8 nmol L−1 Ionized cat: <0.8–0.7 nmol L−1 Ionized cat: <0.7 nmol L−1
Ionized cat: <LLN–0.9 nmol L−1
Calcium, high >ULN to <12.0 mg dL−1 ≥12.0 − 13.0 mg dL−1 >13.0 mg dL−1 Life-threatening, require immediate Death
Ionized: >ULN–1.5 nmol L−1 Ionized: >1.5–1.6 nmol L−1 , mild Ionized: >1.6–1.8 nmol L−1 with patient intervention
clinical signs not requiring clinical signs and/or sequela
immediate intervention requiring medical intervention;
hospitalization indicated
VCOG-CTCAE v1.1
17

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
 18 VCOG-CTCAE v1.1

METABOLIC/LABORATORY (CONTINUED)

Grade
Adverse Event 1 2 3 4 5

CPK >ULN to 2.5× ULN >2.5–5× ULN >5–10× ULN >10× ULN —
Creatinine >1–1.5× baseline; >1.5–3× baseline; >3× baseline; >2.0–3× ULN >3× ULN —
>ULN to 1.5× ULN >1.5–2.0× ULN
Glucose, high Dog: Dog: Dog: Dog: —
>ULN–160 mg dL−1 >160–250 mg dL−1 >250–500 mg dL−1 >500 mg dL−1
Cat: Cat: Cat: Cat:
>ULN–200 mg dL−1 >200–250 mg dL−1 >250–500 mg dL−1 >500 mg dL−1
Glucose, low <LLN to 55 mg dL−1 <55–40 mg dL−1 <40–30 mg dL−1 <30 mg dL−1 Death
Haemoglobinuria Present — — —
Lipase >ULN to 1.5× ULN >1.5–2.0× ULN >2.0–5× ULN >5× ULN
Potassium, high >ULN–5.5 mmol L−1 >5.5–6.0 mmol L−1 >6.0–7.0 mmol L−1 >7.0 mmol L−1 Death
Potassium, low <LLN–3.0 mmol L−1 — <3.0–2.5 <2.5 Death
Phosphorous, high >ULN–8.9 mg dL−1 9.0–12.9 mg dL−1 13.0–18.9 mg dL−1 >19.0 mg dL−1 Death
Tumour lysis syndrome Asymptomatic, Mild to moderate clinical signs, Medical intervention, hospitalization Life-threatening consequences; Death
clinicopathological finding medical intervention indicated >48 h indicated urgent intervention indicated
≤48 h
Definition: A disorder characterized by metabolic abnormalities that result from a spontaneous or therapy-related cytolysis of tumour cells.
Other (Specify, ) Mild Moderate Severe Life-threatening; disabling Death

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
 MUSCULOSKELETAL/SOFT TISSUE

Grade
Adverse Event 1 2 3 4 5

Arthritis, non-septic Mild pain with inflammation or Moderate pain with inflammation or Severe pain with inflammation or Disabling —
joint swelling, but not joint swelling interfering with joint swelling and interfering
interfering with function function, but not interfering with with ADL
ADL
Definition: A disorder characterized by inflammation involving a joint.
Extremity Stands normally, slight lameness Stands normally, noticeable Stands abnormally, severe Non-weight bearing lameness —
(gait/ambulation) when walking lameness when walking, or lameness with stride modified,
lameness limitation of limb function, but occasionally weight bears on
able to walk unassisted involved limb
Definition: Inability to walk normally because of an injury or illness affecting the limbs.
Joint effusion Clinical or diagnostic observations Limiting ADL, medical intervention Severe symptoms; limiting ADL; — —
only; intervention not indicated indicated operative intervention
indicated; disabling
Definition: A disorder characterized by excessive fluid in a joint.
Muscle weakness, Asymptomatic, weakness on Symptomatic and interfering with Symptomatic and interfering with Life-threatening; disabling Death
generalized or specific physical examination function, but not interfering with ADL
area ADL
Definition: A disorder characterized by a reduction in the strength of the muscles.
Myositis (inflammation Mild pain, not interfering with Pain interfering with function, but Pain interfering with ADL Disabling Death
of muscle) function not interfering with ADL
Definition: A disorder characterized by inflammation involving the skeletal muscles.
Seroma Mild erythema; swelling Moderate erythema or swelling; pain Severe erythema or swelling or Open, ulceration or necrosis
pain
Definition: A disorder characterized by a tumour-like collection of serum in the tissues.
Soft tissue necrosis Minor signs of soft tissue damage, Local wound care; medical Operative debridement or other Life-threatening; major invasive Death
no intervention indicated intervention indicated invasive intervention indicated intervention indicated (e.g.
reconstruction, graft)
Definition: A disorder characterized by a necrotic process occurring in the soft tissues.
Other (Specify, ) Mild Moderate Severe Life-threatening; disabling Death
VCOG-CTCAE v1.1
19

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
 NEUROLOGY

Grade
Adverse Event 1 2 3 4 5
20 VCOG-CTCAE v1.1

Apnea — — Present Intubation indicated Death

Definition: A disorder characterized by cessation of breathing.
Ataxia Asymptomatic Symptomatic, not interfering with ADL Symptomatic, interfering with ADL Disabling Death
Definition: A disorder characterized by lack of coordination of muscle movements resulting in the impairment or inability to perform voluntary activities.
Cerebral oedema — — — Life-threatening consequences; urgent Death
intervention indicated
Definition: A disorder characterized by swelling due to an excessive accumulation of fluid in the brain.
Encephalopathy — Mild signs or symptoms; not interfering Signs or symptoms interfering with Life-threatening; disabling Death
with ADL ADL; hospitalization indicated
Definition: A disorder characterized by a pathological process involving the brain.
Irritability Mild; easily consolable Moderate; requiring increased attention Severe; inconsolable — —
Definition: A disorder characterized by an abnormal responsiveness to stimuli or physiological arousal; may be in response to pain, fright, a drug, an emotional situation or a medical condition.
Laryngeal nerve Asymptomatic; clinical Symptomatic, but not interfering with Symptomatic, interfering with ADL; Life-threatening; tracheostomy indicated Death
dysfunction examination finding ADL; intervention not indicated intervention indicated
Definition: A disorder characterized by abnormal laryngeal function.
Neuropathy : Asymptomatic, detected on Symptomatic, not interfering with ADL Symptomatic, interfering with ADL Life-threatening; disabling Death
Cranial nerve examination/testing only
Select:
CNI CNVII CNIII
CNIV CNV CNVI
CNVII CNVIII
CNIX
CNX CNXI CNXII
Neuropathy: Motor Asymptomatic; weakness on Symptomatic weakness interfering with Weakness interfering with ADL Life-threatening; disabling (e.g. paralysis) Death

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
examination/testing only function but not ADL
Neuropathy: Asymptomatic; loss of deep Sensory alteration or paresthesia, Sensory alteration or paresthesia Disabling Death
Sensory tendon reflexes or interfering with function but not ADL interfering with ADL
paresthesia but not
interfering with function
 NEUROLOGY (CONTINUED)

Grade
Adverse Event 1 2 3 4 5

Personality/behaviour Change noticed but not Change, adversely affecting patient or Change is harmful to others or self; — —
adversely affecting patient or family affects ADL
family
Seizure — One brief generalized seizure; well Seizures in which consciousness is Seizures of any kind which are Death
controlled by anticonvulsants or altered; poorly controlled seizure prolonged, repetitive, or
infrequent focal motor seizures not disorder with breakthrough seizures difficult to control (e.g. status
interfering with ADL despite medical intervention epilepticus, intractable epilepsy)
Definition: A disorder characterized by sudden, involuntary skeletal muscular contractions of cerebral or brain stem origin.
Somnolence/depressed — Somnolence or sedation interfering with Obtundation or stupor; difficult to Coma Death
level of function but not ADL arouse; interfering with ADL
consciousness/dullness
Definition: A disorder characterized by excessive sleepiness and drowsiness.
Syncope (fainting) — — Present Life-threatening Death
Definition: A disorder characterized by spontaneous loss of consciousness caused by insufficient blood supply to the brain.
Tremor Mild and brief or intermittent Moderate and brief or intermittent Severe and/or frequent tremor Disabling —
but not interfering with tremor interfering with function, but interfering with ADL
function not interfering with ADL
Definition: A disorder characterized by the uncontrolled shaking movement of the whole body or individual parts.
Other (Specify, ) Mild Moderate Severe Life-threatening; disabling Death
VCOG-CTCAE v1.1
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© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
 OCULAR/VISUAL

Grade
Adverse Event 1 2 3 4 5

Cataract Asymptomatic, detected on Symptomatic with moderate Symptomatic with marked decrease — —
examination only decrease in visual acuity in visual acuity; operative
22 VCOG-CTCAE v1.1

intervention indicated
Definition: A disorder characterized by partial or complete opacity of the crystalline lens of one or both eyes. This results in a decrease in visual acuity and eventual blindness if untreated.
Conjunctivitis/ocular Asymptomatic or minimally Symptomatic, significant discharge; Symptomatic and interfering with — —
surface disease symptomatic but not interfering interfering with function but not ADL; operative intervention
with function ADL; topical antibiotics or other indicated
topical intervention indicated
Definition: A disorder characterized by inflammation, swelling and redness to the conjunctiva of the eye.
Dry eye syndrome Mild, intervention not indicated Symptomatic, interfering with Symptomatic or decrease in visual — —
function but not ADL; medical acuity interfering with ADL
intervention indicated
Definition: A disorder characterized by dryness of the cornea and conjunctiva.
Epiphora Symptomatic, intervention not Symptomatic, interfering with Symptomatic, interfering with ADL — —
indicated function but not ADL
Definition: A disorder characterized by excessive watering of the eye.
Glaucoma Elevated intraocular pressure EIOP causing early visual field deficit; EIOP causing marked visual deficits; EIOP resulting in blindness; —
(EIOP) with single topical agent multiple topical or oral agents operative intervention indicated enucleation indicated
for intervention; no visual deficit indicated
Definition: A disorder characterized by an increase in pressure in the eyeball due to obstruction of the aqueous humour outflow.
Keratitis (corneal Abnormal ophthalmologic Symptomatic and interfering with Symptomatic and interfering with Perforation or blindness —
inflammation/corneal changes only; intervention not function, but not ADL ADL; operative intervention
ulceration) indicated indicated
Definition: A disorder characterized by inflammation to the cornea of the eye.
Optic disc oedema Asymptomatic Symptomatic with moderate Blindness in one but not both eyes Bilateral blindness —
(papilloedema) decrease in visual acuity

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Definition: A disorder characterized by oedema and swelling of the optic disc.
Retinal detachment Exudative; no central vision loss; Exudative and some visual acuity Rhegmatogenous or exudative Blindness —
intervention not indicated loss but intervention not detachment; operative
indicated intervention indicated
Definition: A disorder characterized by the separation of the inner retina layers from the underlying pigment epithelium.
Retinopathy Asymptomatic Symptomatic with moderate Symptomatic with marked decrease Blindness —
decrease in visual acuity in visual acuity; disabling;
interfering with ADL
 OCULAR/VISUAL (CONTINUED)

Grade
Adverse Event 1 2 3 4 5

Definition: A disorder involving the retina.

Scleral necrosis/melt Asymptomatic or symptomatic Symptomatic, interfering with Symptomatic, interfering with ADL; Blindness; painful eye with —
but not interfering with function function but not ADL; moderate operative intervention indicated enucleation indicated
decrease in visual acuity; medical
intervention indicated
Definition: A disorder characterized by necrosis of the sclera.
Uveitis Asymptomatic Anterior uveitis; medical Posterior or pan-uveitis; operative Blindness —
intervention indicated intervention indicated
Definition: A disorder characterized by inflammation of the uvea of the eye.
Vitreous haemorrhage Asymptomatic, clinical findings Symptomatic, interfering with Symptomatic, interfering with ADL; — —
only function but not ADL; intervention indicated
intervention not indicated
Definition: A disorder characterized by blood extravasation into the vitreous humour.
Other (Specify, ) Mild Moderate Severe Life-threatening; disabling Death

PAIN

Grade
Adverse Event 1 2 3 4 5

Pain Mild pain not interfering with function; Moderate pain; manageable with Severe pain; manageable with Disabling or uncontrollable pain —
Specify site: manageable with nonsteroidal standard oral analgesics (NSAIDs, systemic analgesics, pain or
anti-inflammatory drug (NSAID) opiates), pain or analgesics interfering analgesics interfering with ADL
with function but not ADL
Definition: A disorder characterized by marked discomfort.
Other Mild Moderate Severe Life-threatening; disabling Death
VCOG-CTCAE v1.1

(Specify, )
23

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
 PULMONARY/RESPIRATORY

Grade
Adverse Event 1 2 3 4 5

Apnea — — Present; medical intervention Life-threatening respiratory or Death

indicated haemodynamic compromise; intubation or
24 VCOG-CTCAE v1.1

urgent intervention indicated

Definition: A disorder characterized by cessation of breathing.
Aspiration Asymptomatic; radiographic Symptomatic; medical Clinical or radiographic signs of Life-threatening respiratory or Death
findings intervention indicated pneumonia or pneumonitis, haemodynamic compromise; intubation or
hospitalization indicated urgent intervention indicated
Definition: A disorder characterized by inhalation of solids or liquids into the lungs.
Bronchospasm, Asymptomatic Symptomatic, not interfering with Symptomatic, interfering with Life-threatening Death
wheezing function function
Definition: A disorder characterized by a sudden contraction of the smooth muscles of the bronchial wall.
Cough Symptomatic, non-narcotic Symptomatic and narcotic Symptomatic and interfering with — —
medication only indicated indicated sleep or ADL
Definition: A disorder characterized by sudden, often repetitive, spasmodic contraction of the thoracic cavity, resulting in violent release of air from the lungs and usually accompanied by a distinctive
sound.
Dyspnoea Dyspnoea on exertion, but can Dyspnoea on exertion and tires Dyspnoea with ADL Dyspnoea at rest; intubation/ventilator Death
walk without tiring upon ambulating indicated
Definition: A disorder characterized by discomfort due to difficulty in breathing.
Oedema, larynx Asymptomatic oedema by Symptomatic oedema, no Stridor; respiratory distress; Life-threatening; tracheotomy, intubation, Death
examination only respiratory distress interfering with ADL indicated
Definition: A disorder characterized by swelling due to an excessive accumulation of fluid in the larynx.
Hypoxia — <O2 saturation with exercise <O2 saturation at rest; continuous Life-threatening; intubation or ventilation Death
O2 supplementation required required
Definition: A disorder characterized by a decrease in the level of oxygen in the body.
Pleural effusion Asymptomatic Symptomatic, intervention with Symptomatic and requiring Life-threatening (e.g. haemodynamic Death

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
(non-malignant) diuretics or single supplemental oxygen, >1 instability or ventilatory support)
thoracocentesis indicated thoracocenteses, continuous
tube drainage or pleurodesis
indicated
Definition: A disorder characterized by an increase in the amounts of fluid within the pleural cavity. Symptoms include shortness of breath, cough and marked chest discomfort.
Pneumonitis/pulmonary Asymptomatic, radiographic Symptomatic, not interfering with Symptomatic, interfering with Life-threatening; ventilatory support indicated Death
infiltrates findings only ADL ADL; O2 indicated
 PULMONARY/RESPIRATORY (CONTINUED)

Grade
Adverse Event 1 2 3 4 5
Definition: A disorder characterized by inflammation focally or diffusely affecting the lung parenchyma.
Pneumothorax Asymptomatic, radiographic Symptomatic; non-operative Sclerosis and/or operative Life-threatening, haemodynamic Death
findings only intervention indicated intervention indicated instability; ventilatory support
Definition: A disorder characterized by abnormal presence of air in the pleural cavity resulting in the collapse of the lung.
Pulmonary oedema Radiologic findings only; minimal Moderate dyspnoea on exertion; Severe dyspnoea or dyspnoea at rest; Life-threatening respiratory Death
dyspnoea on exertion medical intervention oxygen indicated; limiting ADL compromise; urgent
indicated intervention or intubation with
ventilatory support indicated
Definition: A disorder characterized by accumulation of fluid in the lung tissues that causes a disturbance of the gas exchange that may lead to respiratory failure.
Pulmonary fibrosis Minimal, estimated lung volume Patchy or bilateral changes with Dense or widespread Estimated involved lung volume Death
involved <25% estimated lung volume 25 to infiltrates/consolidation with >75%
<50% estimated involved lung volume
≥50 to 75%
Definition: A disorder characterized by the replacement of the lung tissue by connective tissue, leading to progressive dyspnoea, respiratory failure or right heart failure.
Respiratory distress — — Present, intubation not indicated Present, intubation indicated Death
syndrome (acute
respiratory distress
syndrome)
Definition: A disorder characterized by progressive and life-threatening pulmonary distress in the absence of an underlying pulmonary condition, usually following major trauma or surgery.
Tachypnoea (not Respiratory rate up to 60 bpm >60 bpm; increased abdominal O2 indicated Life-threatening; ventilatory support Death
panting) effort indicated
Definition: A disorder characterized by abnormally rapid breathing.
Other Mild Moderate Severe Life-threatening; disabling Death
(Specify, )
VCOG-CTCAE v1.1
25

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
 RENAL/GENITOURINARY

Grade
Adverse Event 1 2 3 4 5

Acute kidney injury Creatinine level increase of >0.3 mg Creatinine >2 but <3× above Creatinine >3× baseline or >4.0 mg Life-threatening consequences; Death
26 VCOG-CTCAE v1.1

dL−1 ; creatinine 1.5–2.0× above baseline dL−1 ; hospitalization indicated dialysis indicated
baseline
Definition: A disorder characterized by the acute loss of renal function and is traditionally classified as pre-renal (low blood flow into kidney), renal (kidney damage) and postrenal causes (ureteral or
bladder outflow obstruction).
Chronic kidney Asymptomatic [creatinine Mild clinical signs [creatinine Transitional clinical signs [creatinine Uremic; creatinine >440 mmol L−1 Death
disease <140 μmol L−1 (<1.6 mg dL−1 ) in 140–249 μmol L−1 (1.6–2.8 mg 250–439 μmol L−1 (2.9–5.0 mg [>5.0 mg dL−1 ], chronic dialysis or
[International cats; <125 μmol L−1 (<1.4 mg dL−1 ) in cats; 125–179 μmol L−1 dL−1 ) in cats; 180–430 μmol L−1 renal transplant indicated
Renal Interest dL−1 ) in dogs] (1.4–2.0 mg dL−1 ) in dogs] (2.1–5.0 mg dL−1 ) in dogs], fluid
Society (IRIS) therapy indicated; dialysis not
stage] indicated
Definition: A disorder characterized by gradual and usually permanent loss of kidney function resulting in renal failure.
Cystitis (haema- Asymptomatic; microscopic Pollakiuria with dysuria; macroscopic Transfusion indicated; pain or Catastrophic bleeding; non-elective Death
turia/pyuria haematuria/pyuria, not requiring haematuria, transient and not antispasmodic medication; bladder intervention indicated
included) attributed drug discontinuation requiring attributed drug irrigation indicated; requiring
discontinuation attributed drug discontinuation
Definition: A disorder characterized by inflammation of the bladder which is not caused by an infection of the urinary tract.
Glucosuria — Present but transient (<2 weeks) Prolonged (>2 weeks) Permanent
Definition: A disorder characterized by the excretion of glucose in the urine.
Incontinence, Occasional (with coughing, sneezing, Spontaneous Interfering with ADL; medical Operative intervention indicated —
urinary etc.,) intervention indicated
Definition: A disorder characterized by insufficient voluntary control over urination
Obstruction, Asymptomatic; radiographic or Symptomatic without hydronephrosis Symptomatic, altered organ function; Life-threatening; organ failure Death
urinary endoscopic finding or renal dysfunction hydronephrosis; operative
intervention indicated

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Definition: A disorder characterized by blockage of the normal flow of contents of the urinary tract.
Proteinuria Urine protein/creatinine ratio >0.5 Urine protein/creatinine ratio ≥ 1.0 Urine protein/creatinine ratio ≥ 1.0 — —
but <1.0 but transient (<14 days in duration) and prolonged (≥14 days duration)
Definition: A disorder characterized by laboratory test results that indicate the presence of excessive protein in the urine. It is predominantly albumin, but also globulin.
Polyuria Greater in frequency or nocturia up to >2× normal but < hourly ≥1× h−1 ; >2 mL kg−1 h−1 urine >3 mL kg−1 h−1 urine production —
2× normal production
 RENAL/GENITOURINARY (CONTINUED)

Grade
Adverse Event 1 2 3 4 5
Definition: A disorder characterized by production of abnormally large volumes of dilute urine.
Pollakiuria Pet asks to be let out more Pet asks to be let out 6–10 Pet asks to be let out >10 times/day; —
frequently but <6 times/day; times/day; any change in any change in frequency that lasts
any change in frequency that frequency that lasts 2–5 days >5 days, medical or surgical
lasts ≤2 days. intervention required
Definition: A disorder characterized by frequent daytime urination.
Stranguria Minimal straining, attempts to Minimal straining, attempts to Excessive straining, makes repeated Life-threatening, urinary obstruction
urinate 1–3 times at a urination urinate >3 times at a urination attempts to urinate, severely and postrenal failure result
event, slightly reduced stream, event, moderately reduced reduced urine stream, signs
signs persist up to 2 days stream, signs persist 2–5 days persist >5 days; medical or
surgical intervention required
Definition: A disorder characterized by straining to urinate.
Urinary — Mild oliguria: <1.0 ml kg−1 h−1 in Oliguria: <0.5 ml kg−1 h−1 in a well Anuria: absence of urine production Death
output – diminished a well hydrated and well hydrated and well perfused
perfused patient, responsive to patient, resistant to medical
medical diuresis diuresis
Definition: A disorder characterized by diminished production of urine.
Urinary retention Hesitancy or dribbling, no Bladder atony requiring transient Bladder atony requiring indwelling Life-threatening consequences; organ Death
(including significant residual volume indwelling catheter <72 h catheter ≥72 h; operative failure
neurogenic bladder) intervention indicated
Definition: A disorder characterized by accumulation of urine within the bladder because of the inability to urinate.
Urine colour change Present — — — —
Other Mild Moderate Severe Life-threatening; disabling Death
(Specify, )
VCOG-CTCAE v1.1
27

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
 NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)
28 VCOG-CTCAE v1.1

Grade
Adverse Event 1 2 3 4 5

Leukaemia secondary to — — — Present Death

oncology chemotherapy
Definition: A disorder characterized by leukaemia arising as a result of the mutagenic effect of chemotherapy agents.
Myelodysplastic syndrome — — — Life-threatening consequences; Death
urgent intervention indicated
Definition: A disorder characterized by insufficiently healthy haematapoietic cell production by the bone marrow.
Treatment-related secondary — — Non-life-threatening benign Acute life-threatening secondary Death
malignancy tumour or malignancy malignancy; blast crisis in
(Specify, ) leukaemia
Definition: A disorder characterized by development of a malignancy most probably as a result of treatment for a previously existing malignancy.
Tumour pain Mild pain not interfering with Moderate pain; manageable with Severe pain; manageable with Disabling or uncontrollable pain —
function; manageable with standard oral analgesics systemic analgesics, pain or
nonsteroidal anti-inflammatory (NSAIDs, opiates), pain or analgesics interfering with ADL
drug (NSAID) analgesics interfering with
function but not ADL
Definition: A disorder characterized by marked discomfort from a neoplasm that may be pressing on a nerve, blocking blood vessels, inflamed or fractured from metastasis.
Neoplasms benign, malignant Clinical or diagnostic observations Moderate; minimal, local or Severe or medically significant but Life-threatening consequences; Death
and unspecified (including only; intervention not indicated noninvasive intervention not immediately urgent intervention indicated
cysts indicated life-threatening; hospitalization
and polyps) or prolongation of existing
Other (Specify, ) hospitalization indicated;

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
limiting ADL
 SEXUAL/REPRODUCTIVE FUNCTION

Grade
Adverse Event 1 2 3 4 5

Fetal death — — — — Foetal loss at any gestational

age
Definition: A disorder characterized by death in utero; failure of the product of conception to show evidence of respiration, heartbeat or definite movement of a voluntary muscle after expulsion from
the uterus, without possibility of resuscitation.
Gynaecomastia Breast enlargement without Breast enlargement with clinical effect — — —
clinical effect on patient on patient
Definition: A disorder characterized by excessive development of the mammary tissue in males.
Infertility/sterility — Male: Oligospermia/low sperm count Male: Sterile/azoospermia — —
Female: Diminished fertility/estrus Female: infertile/anestrous
Definition: A disorder characterized by inability to reproduce.
Mammary gland Mammary abnormality, not Mammary abnormality, functionally — — —
function/lactation functionally significant significant
Definition: A disorder characterized by disturbances in milk production or secretion.
Vaginal discharge Mild Moderate to heavy — — —
(non-infectious)
Definition: A disorder characterized by excess vaginal secretions.
Other Mild Moderate Severe Life-threatening; —
(Specify, ) disabling
VCOG-CTCAE v1.1
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© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
 30 VCOG-CTCAE v1.1

VASCULAR

Grade
Adverse Event 1 2 3 4 5

Capillary leak syndrome — Symptomatic, fluid support not indicated Respiratory compromise or pressor support Life-threatening; ventilatory support indicated Death
Definition: A disorder characterized by leakage of intravascular fluids into the extravascular space. This syndrome is observed in patients who demonstrate a state of generalized leaky capillaries
following shock syndromes, low-flow states, ischaemia–reperfusion injuries, toxemias, medications or poisoning. It can lead to generalized oedema and multiple organ failure.
Lymph leakage — Symptomatic; medical intervention indicated Severe symptoms; radiologic, endoscopic or Life-threatening consequences; urgent Death
elective operative intervention indicated intervention indicated
Definition: A disorder characterized by the loss of lymph fluid into the surrounding tissue or body cavity.
Peripheral arterial — Brief (<24 h) episode of ischaemia managed Recurring or prolonged (>24 h) and/or Life-threatening, disabling and/or associated Death
ischaemia nonsurgically and without permanent invasive intervention indicated with end-organ damage (e.g. limb loss)
deficit
Definition: A disorder characterized by impaired circulation to an extremity.
Phlebitis — Present — — —
Definition: A disorder characterized by inflammation of the wall of a vein.
Thrombosis/thrombus/ — Deep vein thrombosis or cardiac thrombosis; Deep vein thrombosis or cardiac thrombosis; Embolic event including pulmonary embolism Death
embolism intervention not indicated intervention indicated (e.g. anticoagulation, or life-threatening thrombus
lysis, invasive procedure)
Definition: A disorder characterized by occlusion of a vessel by a thrombus that has migrated from a distal site via the blood stream.
Visceral arterial ischaemia — Brief (<24 h) episode of ischaemia managed Prolonged (>24 h) or recurring clinical signs Life-threatening; disabling; evidence of Death
medically and without permanent deficit and/or invasive intervention indicated end-organ damage
Definition: A disorder characterized by a decrease in blood supply due to narrowing or blockage of a visceral (mesenteric) artery.
Other (Specify, ) Mild Moderate Severe Life-threatening; disabling Death

© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x