Chemotherapy Review

Cell cycle specific drugs Cell cycle non specific

S phase M phase G2 phase drugs
Methotrexate Vinca alkaoids Epipodophylotoxins Alkylating agents
Cytarabine Taxanes Bleomycin Anthracyclines
Gemcitabine Platinum compounds
6-mercaptopurine
Hydroxyurea

Common drug combination regimens

Regimen Drugs Indication

BEP Bleomycin, etoposide, platinum Testicular cancer
(cisplatin)
PVB Platinum(cisplatin), vinblastine,
bleomycin
MOPP Mechlorethamine, Hodgkins lymphoma
oncovin(vincristine),
procarbazine, prednisone
ABVD Adriamycin(doxorubicin),
bleomycin, vinblastine,
dacarbazine
R-CHOP Rituximab, Cyclophosphamide,
hydroxydaunorubicin, oncovin,
prednisone
M-VAC Mtx, vinblastine,adriamycin, Ca Bladder
cisplatin
FOLFOX 5-FU, oxaplatin, leucovorin Colon cancer
VAD Vincristine, adriamycin, Multiple myeloma
dexamethasone
CAF Cyclophosphamide, adriamycin, Ca breast
5-FU
CMF Cyclophosphamide, Mtx, 5-FU
 Alkylating agents

Uses Specific toxicity

Mechanism: Alkylation of N7 guanine residues in DNA

Mechlorethamine MOPP- Hodgkin’s disease Myelosuppression

Cyclophosphamide CHOP-Non hodgkins lymphoma Hemorrhagic cystitis
Autoimmune diseases: lupus Cause- acrolein
nephritis Prevn- MESNA
Melphalan Multiple myeloma
Chlorambucil CLL
Busulfan CML Pulmonary fibrosis
(busulfan lung)
Nitrosureas: Carmustine , Brain tumors Renal failure
smustine, lomustine (Glioblastoma multiforme)
Streptozocin Insulinoma
Pancreatic beta cell carcinoma
Thiotepa Ca bladder
Another most common used agents for brain tumors is temozolomide

Methotrexate
Inhibits DHFR- -indirect
inhibition of DNA synthesis
5 FU-
inhibit thymydidylate
synthetase
Cytarabine (Sphase specific)
Inhibit NA polymerase
6-MP
Converted by HGPRT to active
metabolite – inhibits
nucleotide metabolism – base
mispairing
Gemcitabine
Antimetabolites
Uses Specific toxicity
Folate antagonist
Cancers Mucositis
 ALL Crystalluria
 Choriocarcinoma Myelosuppression
 Burkits lymphoma Leucovorin – to rescue normal
 Non hodgkins cells
lymphoma
As immunosuppressants
 Psoriasis
 Rheumatoid arthritis
 Transplantation
 Crohns disease
Therapeutic abortion
Pyrimidine antagonists
Colon cancer-FOLFOX(i.v)
Premalignant keratoses,
superficial basal cell
carcinoma(topical)
AML
Non hodgkins lymphoma
Purine analogues
ALL Myelosuppression
AML
Pancreatic cancer
Non small cell lung cancer
 Natural products

Mechanism Use Toxicity

Vinca alkaloids
Vinblastine Disrupt microtubule PVB- testicular cancer Myelosuppression
Vincristine (oncovin) assembly MOPP- hodgkins Peripheral neuropathy
CHOP- non Hodgkins
Acute leukemia
Vinorelbine Non small cell lung
cancer
Taxanes
Paclitaxel Stabilizes microtubules Ovarian cancer Peripheral neuropathy
to disassembly Kaposi’s sarcoma Hypersensitivity
Docetaxel Prostate cancer
Epipodophylotoxins
Etiposide Inhibit topoisomerase II- BEP - testicular cancer
Teniposide double stranded DNA
breaks
Camptothecins
Topotecan Inhibit topoisomerase I Ovarian cancer

Irinotecan Colorectal cancer Diarrhea

Antibiotics
Doxorubicin DNA intercalation ABVD- hodgkins Cardiomyopathy
(adriamycin) Inhibit topoisomerase II CAF- Ca breast Prevn- Dexrazoxane
Generation of O2 M-VAC Ca bladder
radicals VAD- multiple myeloma
Daunorubicin R-CHOP- hodgkins

Bleomycin DNA fragmentation PVB- testicular cancer Pulmonary fibrosis

Chromosomal Cutaneous toxicity
aberrations
 Biological agent Use
Alpha interferon Hairy cell leukemia
CML
Kaposis sarcoma
Interleukin-2 Metastatic kidney cancer
Thalidomide Brain tumor
TNF modifier Kaposis sarcoma
Multiple myeloma
Imatinib - Tyrosine kinase Inhibitor of bcr-abl CML
oncoprotein
Geftinib , erlotinib Non-small cell lung cancer
Tyrosine kinase Inhibitor of Epidermal growth
factor receptor(EGFR)
Rituximab Non hodgkins lymphoma
Binds to CD20 antigen on b cells ITP
Trastuzumab HER-2 +ve metastatic breast cancer
HER-2
Cetuximab EGFR expressing metastatic colon cancer
EGFR
Bevacizumab metastatic colorectal cancer
Vascular endothelial growth factor(VEGF)

Hormonal agent Use

Prednisone Acute leukemia
MOPP, CHOP- lymphomas
Progestin- megestrol Endometrial carcinoma
Estrogens- diethylstilbestrol Androgen dependent prostate carcinoma
Antiestrogen - Tamoxifen Estrogen Receptor +ve Breast carcinoma
Gonadotrophin releasing hormones – Carcinoma prostate
leuprolide, goserelin
Aromatase inhibitor- aminoglutethimide Estrogen Receptor +ve Breast carcinoma
anastrozole, exemestane
Adjunct agents used in cancer chemotherapy – used mainly to treat complications of cancer
chemotherapeutic agents

Adjunct Agent Use

Leucovorin or citrovorum factor Rescue from methotrexate toxicity
Formyltetrahydrofolic acid
MESNA Prevents hemorrhagic cystis caused by
Mercaptoethane sulfonate cyclophosphamide
Dexrazoxane Prevents cardiotoxicity with doxorubicin
Free radical scavenger
Filgrastim and pegfilgastim Chemotherapy induced leucopenia
granulocyte colony stimulating factor(G-CSF)
Sargromastim Chemotherapy induced leucopenia
Granulocyte/macrophage colony stimulating Patients undergoing Autologous stem cell
factor(GM-CSF) transplantation and high dose chemotherapy
Epoetin alpha (analog of erythropoietin) Anemia caused by chemotherapy or renal
failure
Oprelvekin Chemotherapy induced thrombocytopenia
Interleukin -11
Amifostine Ovarian and non small cell lung cancer-
Used for Cytoprotection reduces nehrotoxicity
Irradiation of head and neck regions- prevents
mucositis
Zeldronic acid Bone metastasis from multiple myeloma
Bisphosphonate – inhibits osteoclastic bone
resorption – induces osteoclast apoptosis