Overview of Lung Cancer

Overview of Lung Cancer
UKALM00505 November 2012
Prescribing information can be found on the last slide
Summary
Aetiology of lung cancer

Incidence (UK vs rest of Europe)
Epidemiology
Diagnosis in the current decade
does histology matter?
Treatment options
Healthy lung
Image taken from Science Photo Library;

http://www.sciencephoto.com/media/311230/enlarge; 2012
Peripheral adenocarcinoma

http://www.sciencephoto.com/media/m1310638/enlarge;2012
Squamous cell carcinoma arising centrally in the lung

http://www.sciencephoto.com/media/m1310688/enlarge;2012
Key signs and symptoms of lung cancer
Most common sites of Cancer Metastasis and their symptoms

Brain
Headaches
Seizures
Vertigo
Lymph nodes
Lymphadenopathy
Common symptoms
Persistent coughing
Coughing up blood
Unexplained breathlessness
Weight loss
Excessive fatigue
Symptoms due to metastasis
Respiratory
Cough
Hemoptysis
Dyspnea
Liver
Hepatomegaly
Jaundice
Skeletal
Pain
Fractures
Headaches
Lymphadenopathy
Hemoptysis
Jaundice
Hepatomegaly
Aetiology of lung cancer
Primary cause is smoking, which is responsible for

about 90% of all cases1
Genetic predisposition only 10% heavy smokers
develop lung cancer2
Suggestion that low tar cigarettes may be the cause
behind incidence of non-squamous cell carcinomas increasing
Exposure to carcinogens in the work place including
asbestos dust (heavily linked with MPM), radon and other
radioactive materials have been linked with lung cancer3
References:
1. National Health Service [homepage on the Internet]. [Accessed 2012 Feb 20th];
Available from http://www.nhs.uk/Conditions/Cancer-of-the-lung/Pages/Causes.aspx
2. Chest Journal [homepage on the Internet]. [Accessed 2012 Feb 24th];
Available from http://chestjournal.chestpubs.org/content/125/5_suppl/86S.full
3. National Cancer Institute [homepage on the Internet]. [Accessed 2012 Feb 20th];
Available from http://www.cancer.gov/cancertopics/factsheet/Risk/radon
Incidence
Lung cancer is the most common cancer in the world4

Estimated 1.61 million new cases, representing 12.7% of all new cancers*
WHO Europe Region (EURO)*5

Incidence
Overall: 417,000
Men: 310,000
Women: 107,000
Mortality
Overall: 367,000
Men: 276,000
Women: 91,000
United Kingdom5
Incidence
Overall: 91.7
Men: 57.1
Women: 34.6
Mortality
Overall: 80.4
Men: 50.7
Women: 29.7
*2008 estimate
Estimated age-standardised incidence and mortality rates (European standard) per 100,000 by site, sex and country, 2006.
References:
4. Globacan, Cancer Incidence: Mortality and Prevalence Worldwide, 2008, 1-5
5. Ferlay J, Estimates of the cancer incidence and mortality in Europe, 2006, Annals of Oncology 2007; 18: 585-586
Graph adapted from http://info.cancerresearchuk.org/cancerstats/types/lung/incidence/#histology
lan
ary
De
d
nm
eN
ark
eth
erl
an
ds
Be
lgi
um
Es
Cz
ton
ec
ia
hR
ep
ub
lic
Slo
Un
v
ite
en
dK
ia
ing
d
Lu
om
xe
mb
ou
rg
Ire
lan
d
EU
-27
Ro
ma
nia
Lit
hu
an
ia
Gr
e
e
Fra
ce
nc
e(
L
a
Me
tvi
a
tro
po
lita
n)
Sp
ain
Slo
va
kia
Bu
lga
ria
Ge
rm
an
y
Ita
ly
Au
str
ia
Fin
lan
d
Ma
lta
Sw
ed
en
Po
rtu
ga
l
Cy
pru
s
Th
Po
ng
Hu
Rate per 100,000
Incidence rates across europe
Lung cancer (C33-34), european age-standardised incidence rates,

EU-27 countries, 2008 estimates
120
Female
Male
90
60
30
Survival by stage
Relative survival for lung cancer in all stages6

50
42
Patients (%)
40
30
16
20
10
1 year
(2002-2005)
5 years
(1999-2005)
References:
6. Cancer Facts and Figures, American Cancer Society, 2010, pg 16.
www.cancer.org/Research/Cancer-facts-and-figures-2010 2010; n/a: 1-68
Accessed: 20th February 2012
5-year survival rates
5-year survival rates according to the 7th edition of TNM7

50
50
43
45
40
36
Patients (%)
35
30
25
25
19
20
15
10
5
0
IA
IB
IIA
IIB
IIIA
IIIB
IV
NSCLC clinical stage

References:
7. Goldstraw P, The IASLC Lung Cancer Staging Project: Proposals for the Revision of the TNM Stage Groupings in the
Forthcoming (Seventh) Edition of the TNM Classification of Malignant Tumours, Journal of Thoracic Oncology 2007; 2: 706-714
NSCLC survival rates across europe 22
Age-standardised 1-year relative survival

42.2
41.1
Age-standardised 5-year relative survival

16.5
Belgium
15
Iceland
14.4
Austria
39.5
38.2
37.4
13.9
Switzerland
13.4
Netherlands
13.2
Germany
36.8
Sweden
36.8
France
12.9
36.7
Italy
12.8
36
Portugal
12.8
35.7
EUROPE
35.1
35
34.2
10.7
Spain
10.2
UK Northern Ireland
32.3
Ireland
32
Finland
31.6
Poland
28.7
10.9
Norway
9.8
9.7
9.2
9
UK Wales
28.4
Slovenia
8.8
28.2
Malta
8.7
27.9
UK England
27.1
Czech Republic
26.9
UK Scotland
Denmark
7.9
26.5
0 5 10 15 20 25 30 35 40 45
8.2
0 2 4 6 8 10 12 14 16 18
Adapted from Reference 22. Sant M Alleman C, EUROCARE-4. Survival of cancer patients diagnosed in 19951999.
Results and commentary; European Journal of Cancer 2009; 45: 93191
Epidemiology
Lung cancer is the most common cancer in the world with

1.61 million new cases diagnosed every year8
One third of all deaths in middle age (ages 35-69) are caused
by cigarettes9
The lifetime risk of developing lung cancer in 2008 is
1 in 14 for men
1 in 19 for women in the UK8
A non-smoking spouse of a regular smoker has a 20% increase
in their chances of developing lung cancer and a 30% increase
in their chance of developing heart disease9
References:
8. Cancer Research UK, Lung Cancer Statistics, [homepage on the Internet] [accessed 2012 Feb 21st]
Available from http://info.cancerresearchuk.org/cancerstats/types/lung/incidence/uk-lung-cancer-incidence-statistics
9. Quit Smoking Support, [homepage on the Internet] [accessed 2012 Feb 20th]
Available from http://www.quitsmokingsupport.com/facts.htm
Types of lung cancer
SCLC
20%
NSCLC
80%
Pie chart adapted from http://info.cancerresearchuk.
org/cancerstats/types/lung/incidence/#histology
NSCLC by histotype
Non-squamous: the predominant histology in JMDB10
n=473
Squamous cell
carcinoma
n=847
Adenocarcinoma
n=252
NOS
n=153
Large cell
carcinoma
10. Scagliotti G, Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients
With Advanced-Stage Non-Small-Cell Lung Cancer: JOURNAL OF CLINICAL ONCOLOGY 2008; 26: 3543-3551
Adenocarcinoma
Data on File, Eli Lilly + Company and/or one of its Subsidiaries
Cell division of adenocarcinoma
Data on File, Eli Lilly + Company and/or one of its Subsidiaries
Diagnosis ...challenges of identifying

the correct histological diagnosis
Image taken from shutterstock

(No. 90348691)
http://www.shutterstock.com


(No. 90348691)


(No. 90348691)


(No. 90348691)


(No. 90348691)


(No. 90348691)


(No. 90348691)


(No. 90348691)


(No. 90348691)


(No. 90348691)


(No. 90348691)


(No. 90348691)


(No. 90348691)


(No. 90348691)


(No. 90348691)
The role of the Histopathologist
Image taken from shutterstock (No. 88351897)

National Lung Cancer Audit: Treating the advanced

NSCLC patient in England and Wales11
76% of patients are receiving a histological/cytological diagnosis

14% of patients are receiving an operation
58% of patients are receiving any active anti-cancer treatment rate
85% of patients are receiving CT scan before bronchoscopy
96% of patients are discussed at MDT
References:
11. National Lung Cancer Audit, Key Messages, The NHS Information Centre: 2011, Leeds
What do most people think when we

say the word chemotherapy?


Attitudes to intensive chemotherapy (% acceptance)12
Cancer Nurses
GPs
RT
13.5
12.4
3.3
Cure (1%)
4.5
Survival increased by 3 months
0
2.4
Symptom relief (1%)

0
5.9
Key:
GP = General Practitioner
RT = Radio Therapist
Onc = Oncologist
References:
12. Slevin M, Attitudes to chemotherapy: comparing views of patients with cancer with
those of doctors, nurses, and general public; BMJ; Vol. 300; JUNE 1990; 1458-1460
Onc
Patients
20
53.1
10.2
42.1
6.8
42.6
Challenging the perception...

Chemotherapy offers significant patient benefit13
GEM + BSC
BSC
50
45
% improvement
40
35
30
25
20
15
10
5
0
Emotional Function
(subscale)
Pain
(symptom scale)
Dyspnoea
(symptom scale)
Chest pain
References:
13. Anderson H, Gemcitabine plus best supportive care (BSC) vs. BSC in inoperable non-small cell lung cancer:
a randomised trial with quality of life as the primary outcome; British Journal of Cancer (2000) 83(4), 447-453
Cough
Fatigue
Major survival milestones in advanced NSCLC
Improvement in median overall survival in advanced disease NSCLC patients14,15,16
1970s
2-4 mos
BSC
1980s
6-8 mos
Single-agent platinum
References:
14. Sandler A, PaclitaxelCarboplatin Alone or with Bevacizumabfor NonSmall-Cell
Lung Cancer; New England Journal of Medicine 2006; 355: 2542-2550
15. Schiller JH, Comparison of four chemotherapy regimens for advanced non-small-cell
lung cancer, New England Journal of Medicine 2002; 346: 92-98
16. Scagliotti G, The differential efficacy of Pemetrexed according to NSCLC histology:
a review of two Phase III studies, Oncologist 2009; 14: 258-260
1990-2005
8-10 mos
Platinum-based doublets
2005-present
12+ mos
Histology-directed therapy
Platinum-based triplet therapy
Maintenance Treatment
Proposed algorithm for advanced NSCLC treatment
Histology
Non-squamous NSCLC
Squamous NSCLC
EGFR testing
No EGFR sensitising
mutatiion or unkown
Pemetrexed
+ Platinum
(4 cycles)
Pemetrexed
+ Platinum
(4 cycles)
EGFR sensitising
mutation
Gefitinib
Stable disease,
PR or CR
Progression
Maintenance
pemetrexed
Erlotinib or Docetaxel
or Pemetrexed
(if patient has not received
any previous pemetrexed)
Doublet chemotherapy
(Platinum + vinorelbine
or gemcitabine
or paclitaxel)
Information adapted from Taylor S, Surrey.

Accessed 26th February.
Chemotherapy Algorithm for Advanced
Non-Small Cell Lung Cancer; 2011
Pemetrexed +/platinum
Afatinib
(compassionate use programme)
for patients with 6 months
response to TKI
http://www.swshcn.nhs.uk/healthcareprofessionals/clinical-policies-and-protocols/
oncology_protocols/healthcare-professionals/
clinical-policies-and-protocols/oncology_
protocols/lung-cancer/NSCLC%20palliative.pdf
Erlotinib or Docetaxel
Alimta 1st line NSCLC study
JMDB: A comprehensive study* in 1st line advanced NSCLC (N=1725)17

Primary endpoint
Secondary endpoints
ALIMTA/cisplatin n=862
500mg/m2 Day 1 q 21 days + cisplatin
75mg/m2 (following ALIMTA)
Randomisation
For a maximum of 6 cycles of therapy + vitamin

supplementation/dexamethasone prophylaxis
Gemcitabine/cisplatin n=863
Prespecified analyses
Included analyses of efficacy according to NSCLC histology
Presecification based on previous clinical data showing
that Alimta efficacy differed according to NSCLC histology,
with improved efficacy in non-squamous patients
*Largest multicentre, randomised, phase III trial
References:
17. Scagliotti G, Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus

Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non-Small-Cell Lung Cancer:

JOURNAL OF CLINICAL ONCOLOGY 2008; 26: 3544,3545,3546
1250mg/m2 Day 1 and Day 8 q 21 days +

cisplatin 75mg/m2 (Day 1 following gemcitabine)
For a maximum of 6 cycles of therapy + vitamin
supplementation/dexamethasone prophylaxis
ALIMTA/cisplatin: Increased survival in 1st line advanced

non-squamous* NSCLC patients 18,19
Survival probability
1.0
0.9
Adenocarcinoma
12.6 months
ALIMTA/cisplatin (n=436)
0.8
Gemcitabine/cisplatin (n=411)
0.7
Adjusted HR 0.84
(95% CI: 0.71-0.99)
p=0.03
10.9 months
12.6
months
0.6
0.5
0.4
0.3
0.2
0.1
0.0
12
18
24
30
Survival time (months)

*Adenocarcinoma, large cell carcinoma and other histlologies.
Compared with gemcitabine/cisplatin.

Note: Overall survival in patients with histology not otherwise specified (n=252) was 8.6 months with ALIMTA/cisplatin
vs 9.2 months with gemcitabine/cisplatin (HR 1.08; 95% CI: 0.81-1.45; p=0.586).
References:
18. Scagliotti G, The differential efficacy of Pemetrexed according to NSCLC histology: a review of two Phase III studies, Oncologist 2009; 14: 258-260
19. Alimta SPC; 16-17, 2011; Eli Lilly and Company

1.0
Adenocarcinoma
1-yr survival
0.9
51%
0.8
45%
0.7
51%
0.6
1-yr survival
0.5
0.4
0.3
0.2
0.1
0.0
12
18
24
30


References:

1.0
Adenocarcinoma
2-yr survival
0.9
26%
0.8
18%
0.7
0.6
0.5
26%
0.4
2-yr survival
0.3
0.2
0.1
0.0
12
18
24
30


References:
ALIMTA/cisplatin: Significant tolerability advantages*

in 1st line advanced NSCLC20
Grades 3/4 haematologic toxicities
30
26.7
25
Patients (%)
20
15.1
15
12.7
9.9
10
7.6
5.6
4.1
4.8
Neutropenia
p<0.001
Anaemia
(haemoglobin)
p=0.001
Thrombocytopenia
(platelets)
p<0.001
*Compared with gemcitabine/cisplatin.
Only drug-related toxicities reported in at least 3% of patients on at least one arm are listed.
Haematologic
Non-haematologic
References:
20. Scagliotti G, Phase III Study Comparing Cisplatin Plus Gemcitabine with Cisplatin Plus Pemetrexed in Chemotherapy-Naive

Patients with Advanced-Stage Non-Small-Cell Lung Cancer: JOURNAL OF CLINICAL ONCOLOGY 2008; 26: 3543-3551
Leukopenia
p=0.019
ALIMTA/cisplatin: Significant tolerability advantages*

in 1st line advanced NSCLC21
Grades 3/4 non-haematologic toxicities
30
25
Patients (%)
21.4
20
15
10
7.2
3.9
6.1 6.1
2.0
3.6
4.9
6.7
3.7
1.3
Nausea
p=0.004
Vomiting
p=1.000
Dehydration
(any grade)
p=0.075
Fatigue
p=0.143
Alopecia
(any grade)
p<0.001
*Compared with gemcitabine/cisplatin.
Unless otherwise specified.
Only drug-related toxicities reported in at least 3% of patients on at least one arm are listed.
Haematologic
Non-haematologic
References:
21. Scagliotti G, Phase III Study Comparing Cisplatin Plus Gemcitabine with Cisplatin Plus Pemetrexed in Chemotherapy-Naive

Patients with Advanced-Stage Non-Small-Cell Lung Cancer: JOURNAL OF CLINICAL ONCOLOGY 2008; 26: 3543-3551
Febrile
neutropenia
p=0.002
Supplementation
Vitamins Timeline
1st Cycle
Vitamin B12
2nd Cycle
3rd Cycle
Folic Acid
Alimta SPC; 2011; Eli Lilly and Company

KEY:
Vitamin B12: 1000mcg should be given IM in the seven days prior
to the first cycle of Alimta. This should be repeated prior to or on
the day of the 4th Alimta cycle and every 3 cycles thereafter.
Folic Acid: 350-1000mcg of oral Folic acid should be taken daily
for 5 days out of 7 before the first Alimta cycle. This should be
continued until 21 days after the final cycle.
Dexamethasone: 4mg should be given orally BD, the day before,
the day of and the day after Alimta administration.
4th Cycle
5th Cycle
6th Cycle
Dexamethasone
NSAIDs
Patients should avoid taking NSAIDs 2 days
before (5 days for long acting) the day of and
two days after a cycle of Alimta treatment.
PARAMOUNT: Study Design1,2
Study Treatment Period

Progression
Induction Therapy (4 cycles)
21 to 42 Days
Maintenance Therapy (Until PD)
500 mg/m2 ALIMTA + BSC, d1, q21d

Patients enrolled if:
Nonsquamous* NSCLC
No prior systemic treatment for
lung cancer
ECOG PS 0/1
500 mg/m2 ALIMTA +

75 mg/m2 Cisplatin, d1, q21d
CR,
PR, SD
2:1 Randomisation
Placebo + BSC, d1, q21d
Stratified for:
PS(0 vs 1)
Disease stage (IIIB vs IV) prior to induction
Response to induction (CR/PR vs SD)
PD
Randomised, placebo-controlled, double-blind, phase III study
Folic acid, vitamin B12 and dexamethasone administered to both arms
*Includes adenocarcinoma, large cell, and other histologies except those with squamous cell type.
References:
1. Paz-Ares LG. Oral Presentation presented at the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Related to Abstract CRA7510.
2. ALIMTA Summary of Product Characteristics. Eli Lilly and Company Limited. November 2011.
PARAMOUNT: Final Overall Survival From Induction1
1.0
0.9
OS median
(95% CI)
0.8
Unadjusted HR
(95% Cl)
0.7
Log-rank p-value
ALIMTA+ BSC
Placebo + BSC
16.9 mos
(15.819.0)
14.0 mos
(12.915.5)
0.78 (0.640.96)
0.0191
0.6
0.5
0.4
0.3
0.2
0.1
0.0
12
15
18
21
24
27
Survival time from induction (months)
References:
1.Paz-Ares LG. Oral Presentation presented at the American Society of Clinical Oncology; June 1-5, 2012; Chicago, IL. Abstract LBA7507
30
33
36
Prescribing information
ALIMTA* (PEMETREXED DISODIUM) ABBREVIATED PRESCRIBING INFORMATION Presentation Type I glass vials with
rubber stoppers containing pemetrexed disodium equivalent to 100 and 500mg of pemetrexed, as a sterile white to either
light yellow or green-yellow lyophilised powder. Uses Alimta in combination with cisplatin is indicated for the treatment of
chemotherapy naive patients with unresectable malignant pleural mesothelioma. Alimta in combination with cisplatin is
indicated for first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than
predominantly squamous cell histology. Alimta is indicated as monotherapy for the maintenance treatment of locally
advanced or metastatic non-small cell lung cancer, other than predominantly squamous cell histology, in patients whose
disease has not progressed immediately following platinum-based chemotherapy. Alimta is indicated as monotherapy for
the second-line treatment of patients with locally advanced or metastatic non small cell lung cancer, other than
predominantly squamous cell histology. Dosage and Administration Posology: The drug is to be administered
intravenously, under the supervision of a physician qualified in the use of cytotoxic anti cancer therapy. Alimta in combination
with cisplatin: The recommended dose of pemetrexed is 500mg/m of body surface area (BSA), given by ten-minute infusion,
on day 1 of each 21-day cycle. The recommended dose of cisplatin is 75mg/m BSA, given by two-hour infusion,
approximately 30 minutes after completion of the pemetrexed infusion on day 1 of each cycle. Adequate anti-emetic
treatment and hydration for cisplatin treatment must be given. Alimta as single agent: The recommended dose of pemetrexed
is 500mg/m BSA, given by ten-minute infusion, on day 1 of each 21-day cycle. Pre-medication: Supplement with 1000
micrograms intramuscular vitamin B12 and oral folic acid (350 to 1000 micrograms) to reduce toxicity (for full details see
Summary of Product Characteristics [SPC]). To reduce the incidence and severity of skin reactions, a corticosteroid should
be given the day prior to, on the day of, and the day after pemetrexed administration - this should be equivalent to 4mg of
dexamethasone administered orally twice a day. Monitoring: Monitor prior to each dose for complete blood cell count,
including a differential white cell count and platelet count. Absolute neutrophil count should be 1,500 cells/mm3 and
platelets 100,000 cells/mm3. Prior to each dose, collect blood chemistry tests to evaluate renal and hepatic function. Dose
adjustments to pemetrexed and/or cisplatin at the start of a subsequent cycle should be based on nadir haematological
counts or maximum non haematological toxicity. If necessary, delay or withhold treatment in the presence of haematological
toxicity, neurotoxicity, and/or impaired hepatic/renal function. (For full information on dose modification see SPC.) Paediatric
population: There is no relevant use of Alimta in the paediatric population in malignant pleural mesothelioma and non-small
cell lung cancer. Renal impairment: Patients with creatinine clearance 45ml/min require no dose adjustment other than
those recommended for all patients. Use in patients with creatinine clearance below 45ml/min is not recommended. See
also Warnings and Special Precautions. Hepatic impairment: Patients with hepatic impairment, such as bilirubin >1.5-times
the upper limit of normal and/or aminotransferase >3.0-times the upper limit of normal (hepatic metastases absent) or >5.0times the upper limit of normal (hepatic metastases present), have not been specifically studied. Method of administration:
Precautions should be taken before handling or administering Alimta. Alimta should be administered as an intravenous
infusion over 10 minutes on the first day of each 21-day cycle. For instructions on reconstitution and dilution of Alimta before
administration, see SPC. Contra-indications Hypersensitivity to pemetrexed or to any of the excipients. Concomitant
yellow fever vaccine. Breast-feeding. Warnings and Special Precautions Myelosuppression is usually the dose-limiting
toxicity. All patients must be instructed to take folic acid and vitamin B12 as a prophylactic measure. Pre-treatment with
dexamethasone (or equivalent) can reduce the incidence and severity of skin reactions. Serious renal events, including acute
renal failure, have been reported with pemetrexed alone or in combination with other chemotherapeutic agents. Many of the
patients in whom these occurred had underlying risk factors, including dehydration or pre-existing hypertension or diabetes.
The effect of third space fluid, such as pleural effusion or ascites, on pemetrexed is not fully defined. A Phase 2 study of
pemetrexed in 31 solid tumour patients with stable third space fluid demonstrated no difference in pemetrexed dose
normalised plasma concentrations or clearance compared to patients without third space fluid collections. Thus, drainage
of third space fluid collection prior to pemetrexed treatment should be considered, but may not be necessary. Serious
cardiovascular events, including myocardial infarction and cerebrovascular events, have been uncommonly reported when
pemetrexed is given in combination with other cytotoxic agents; most of these patients had pre-existing cardiovascular risk.
Concomitant use of live attenuated vaccines is not recommended. Radiation pneumonitis has been reported in patients
treated with radiation either prior, during, or subsequent to pemetrexed therapy. Pay particular attention to these patients
and exercise caution with use of other radiosensitising agents. Radiation recall has been reported in patients who received
radiotherapy weeks or years previously. Interactions Concomitant administration of nephrotoxic drugs and substances that
are also tubularly secreted could potentially result in delayed clearance of pemetrexed. If necessary, creatinine clearance
should be closely monitored. Patients must avoid taking non-steroidal anti-inflammatory drugs (NSAIDs) with long
elimination half-lives for at least 5 days prior to, on the day, and at least 2 days following pemetrexed administration. If
concomitant administration of NSAIDs is necessary, patients should be monitored closely for toxicity, especially
myelosuppression and gastro-intestinal toxicity. In patients with normal renal function (creatinine clearance 80ml/min), high
doses of NSAIDs (such as ibuprofen >1600mg/day) and aspirin at higher dosage (1.3g daily) may decrease pemetrexed
elimination and increase the occurrence of adverse events. Patients with mild to moderate renal insufficiency (creatinine
clearance from 49 to 79ml/min) should avoid taking NSAIDs (eg, ibuprofen) or aspirin at higher dosage, for 2 days before,
on the day of, and 2 days following pemetrexed administration. In patients with mild to moderate renal insufficiency eligible
for pemetrexed therapy, NSAIDs with long elimination half-lives should be interrupted for at least 5 days prior to, on the day
of, and at least 2 days following pemetrexed administration. There is a possible interaction between oral anticoagulants and
pemetrexed; therefore, increase the frequency of International Normalised Ratio (INR) monitoring if treating with oral
anticoagulants. Fertility, Pregnancy and Lactation Contraception in males and females: Women of childbearing potential
must use effective contraception during treatment with pemetrexed. Pemetrexed can have genetically damaging effects.
Sexually mature males are advised not to father a child during the treatment and up to 6 months thereafter. Contraceptive
measures or abstinence are recommended. Pregnancy: There are no data from the use of pemetrexed in pregnant women
but pemetrexed, like other anti metabolites, is suspected to cause serious birth defects when administered during
pregnancy. Animal studies have shown reproductive toxicity. Pemetrexed should not be used during pregnancy unless
clearly necessary, after a careful consideration of the needs of the mother and the risk for the foetus. Breastfeeding: It is not
known whether pemetrexed is excreted in human milk and adverse reactions on the suckling child cannot be excluded.
Breast-feeding must be discontinued during pemetrexed therapy. Fertility: Owing to the possibility of pemetrexed treatment
causing irreversible infertility, men are advised to seek counselling on sperm storage before starting treatment. Driving, etc
It has been reported that pemetrexed may cause fatigue. Patients should be cautioned against driving or operating
machinery. Undesirable Effects Summary of the safety profile: The most commonly reported undesirable effects related to
pemetrexed, whether used as monotherapy or in combination, are bone marrow suppression, manifested as anaemia,
neutropenia, leucopenia, and thrombocytopenia; and gastro-intestinal toxicities, manifested as anorexia, nausea, vomiting,
diarrhoea, constipation, pharyngitis, mucositis, and stomatitis. Other undesirable effects include renal toxicities, increased
aminotransferases, alopecia, fatigue, dehydration, rash, infection/sepsis, and neuropathy. Rarely seen events include
Stevens-Johnson syndrome and toxic epidermal necrolysis. Rare cases of anaphylactic shock have been reported.
Infections and infestations: Common: Infection. Haematological: Very common: Anaemia, leucopenia, thrombocytopenia,
neutropenia. Common: Febrile neutropenia and infection without neutropenia. Uncommon: Pancytopenia. Rarely,
haemolytic anaemia has been reported in patients treated with pemetrexed. Gastro-intestinal: Very common: Nausea,
vomiting, stomatitis/pharyngitis, anorexia, diarrhoea, constipation. Common: Dyspepsia, abdominal pain, heartburn.
Uncommon: Colitis (including bleeding, sometimes fatal, intestinal perforation, intestinal necrosis, and typhlitis).
Oesophagitis/radiation oesophagitis has been reported during trials. General: Very common: Fatigue. Common: Fever,
conjunctivitis, pain, oedema. Metabolism and nutrition: Common: Dehydration. Nervous system: Very common: Neuropathy
- sensory. Common: Neuropathy - motor, dizziness, taste disturbance. Renal and urinary: Very common: Creatinine elevation,
creatinine clearance decreased. Common: Renal failure, renal disorders. Hepatobiliary: Common: SGPT (ALT) elevation and
SGOT (AST) elevation, increased GGT. Rare: Cases of hepatitis, potentially serious, have been reported during trials. Skin
and subcutaneous tissue: Very common: Rash/desquamation, alopecia. Common: Urticaria, allergic reaction/hypersensitivity,
erythema multiforme, pruritus. Rare: Radiation recall; bullous conditions have been reported, including Stevens-Johnson
syndrome and toxic epidermal necrolysis, which in some cases were fatal. Uncommon: Cases of peripheral ischaemia,
leading sometimes to extremity necrosis, have been reported. Cardiovascular and cerebrovascular: Uncommon: Myocardial
infarction, angina pectoris, cerebrovascular accident, supraventricular arrhythmias, transient ischaemic attack, pulmonary
embolism. (Usually when given in combination with other cytotoxic agents and with pre-existing cardiovascular risk.)
Common: Chest pain. Respiratory: Uncommon: Interstitial pneumonitis with respiratory insufficiency (sometimes fatal),
radiation pneumonitis. For full details of these and other side-effects, please see the Summary of Product Characteristics,
which is available at http://emc.medicines.org.uk/. Legal Category POM Marketing Authorisation Numbers
EU/1/04/290/001, EU/1/04/290/002 Basic NHS Cost 100mg vial: 160.00 per pack of 1 vial, 500mg vial: 800.00 per pack
of 1 vial Date of Preparation or Last Review November 2012 Full Prescribing Information is Available From Eli Lilly and
Company Limited, Lilly House, Priestley Road, Basingstoke, Hampshire, RG24 9NL Telephone: Basingstoke (01256) 315 000
E-mail: ukmedinfo@lilly.com Website: www.lillypro.co.uk *ALIMTA (pemetrexed disodium) is a trademark of Eli Lilly and
Company.
UKALM00505 November 2012
Adverse events should be reported. Reporting forms and further information

can be found at: www.mhra.gov.uk/yellowcard.
Adverse events and product complaints should also be reported to Lilly:
please call Lilly UK on 01256 315 000.

Overview of Lung Cancer

Încărcat de

Informații document

Descriere originală:

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

Overview of Lung Cancer

Încărcat de

Drepturi de autor:

Formate disponibile

Overview of Lung Cancer

UKALM00505 November 2012

Prescribing information can be found on the last slide

Aetiology of lung cancer

Image taken from Science Photo Library;

Image taken from Science Photo Library;

Squamous cell carcinoma arising centrally in the lung

Image taken from Science Photo Library;

Key signs and symptoms of lung cancer

Most common sites of Cancer Metastasis and their symptoms

Symptoms due to metastasis

Aetiology of lung cancer

Primary cause is smoking, which is responsible for

Lung cancer is the most common cancer in the world4

WHO Europe Region (EURO)*5

Graph adapted from http://info.cancerresearchuk.org/cancerstats/types/lung/incidence/#histology

Rate per 100,000

Incidence rates across europe

Lung cancer (C33-34), european age-standardised incidence rates,

Relative survival for lung cancer in all stages6

5-year survival rates

5-year survival rates according to the 7th edition of TNM7

NSCLC clinical stage

NSCLC survival rates across europe 22

Age-standardised 1-year relative survival

Age-standardised 5-year relative survival

Lung cancer is the most common cancer in the world with

Types of lung cancer

Non-squamous: the predominant histology in JMDB10

Data on File, Eli Lilly + Company and/or one of its Subsidiaries

Cell division of adenocarcinoma

Data on File, Eli Lilly + Company and/or one of its Subsidiaries

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

Diagnosis ...challenges of identifying

Image taken from shutterstock

The role of the Histopathologist