CANCER CHEMOTHERAPY
ACRONYM OF REGIMEN
Hodgkin's lymphoma ABVD Adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine
(stage 3 & 4)
BEACOPP Bleomycin, etoposide, Adriamycin (doxorubicin), cyclophosphamide, Oncovin (vincristine), procarbazine, prednisone
MOPP Mechlorethamine, Oncovin (vincristine), procarbazine, prednisone
Stanford V Doxorubicin, mechlorethamine, bleomycin, vinblastine, vincristine, etoposide, prednisone
VAPEC-B Vincristine, Adriamycin (doxorubicin), prednisone, etoposide, cyclophosphamide, bleomycin
Non-Hodgkin lymphoma, CLL CHOP Cyclophosphamide, hydroxydoxorubicin (doxorubicin), vincristine (Oncovin), prednisone (TOC)
m-BACOD Methotrexate, bleomycin, Adriamycin (doxorubicin), cyclophosphamide, Oncovin (vincristine), dexamethasone
MACOP-B Methotrexate, leucovorin (folinic acid), Adriamycin (doxorubicin), cyclophosphamide, Oncovin (vincristine), prednisone,
bleomycin
COPP Cyclophosphamide, Oncovin (vincristine), procarbazine, prednisone
Non-Hodgkin lymphoma in COP or CVP Cyclophosphamide, Oncovin (vincristine), prednisone
patients with history of
cardiovascular disease
B cell non-Hodgkin lymphoma CHOP-R or R- CHOP + rituximab
CHOP
R-FCM Rituximab, fludarabine, cyclophosphamide, mitoxantrone
Lymphoma CBV Cyclophosphamide, BCNU (carmustine), VP-16 (etoposide)
EPOCH Etoposide, prednisone, Oncovin, cyclophosphamide, and hydroxydaunorubicin
Aggressive lymphomas, ICE ifosfamide, carboplatin, etoposide (VP-16)
progressive neuroblastoma
High-risk progressive or ICE-R ICE + rituximab
recurrent lymphomas
Breast cancer AC Adriamycin (doxorubicin), cyclophosphamide
CA Cyclophosphamide, Adriamycin (same as AC)
CAF Cyclophosphamide, Adriamycin , fluorouracil (5-FU)
CMF Cyclophosphamide, methotrexate, fluorouracil (5-FU)
EC Epirubicin, cyclophosphamide
FEC Fluorouracil (5-FU), epirubicin, cyclophosphamide
Colorectal cancer FL (Aka- Mayo) Fluorouracil (5-FU), leucovorin (folinic acid)
FOLFOX Fluorouracil (5-FU), leucovorin (folinic acid), oxaliplatin
FOLFIRI Fluorouracil (5-FU), leucovorin (folinic acid), irinotecan
Testicular cancer, germ cell BEP Bleomycin, etoposide, platinum agent (cisplatin)
tumors
EP Etoposide, platinum agent (cisplatin)
VIP Etoposide, ifosfamide, platinum agent cisplatin
TIP Paclitaxel, ifosfamide, platinum agent cisplatin
Multiple myeloma Thal/Dex Thalidomide, dexamethasone
VAD Vincristine, Adriamycin (doxorubicin), dexamethasone
Brain tumors PCV Procarbazine, CCNU (lomustine), vincristine
Lung cancer CAV Cyclophosphamide, Adriamycin (doxorubicin), vincristine
Rhabdomyosarcoma VAC Vincristine, Actinomycin, Cyclophosphamide
Gastric cancer and ECF Epirubicin, cisplatin, fluorouracil (5-FU)
oesophageal cancer
Sarcoma MAID Mesna, Adriamycin (doxorubicin),ifosfamide, dacarbazine
LOG KILL HYPOTHESIS
According to the log-kill hypothesis, chemotherapeutic agents kill a constant fraction of cells (first order kinetics), rather than a specific number of cells, after each dose
1. Solid cancer tumors - generally have a low growth fraction thus respond poorly to chemotherapy & in most cases need to be removed by surgery
2. Disseminated cancers- generally have a high growth fraction & generally respond well to chemotherapy.
The tumor is detected (using conventional techniques) when the tumor burden reaches 10 9 cells
The patient is symptomatic at 1010-1011 cells
Dies at 1012 cells.
EFFECT OF CELL CYCLE
CELL CYCLE SPECIFIC AGENTS (CCS) CELL CYCLE NONSPECIFIC AGENTS
(CCNS)
Kills cells in cell cycle KILLS BOTH G0 and cycling cells (although cycling cells are more specific)
Useful in High growth fraction tumors (hematological malignancies, Burkitt’s lymphoma, Useful in both High growth fraction & low growth fraction tumors (solid
trophoblastic choriocarcinoma) tumors)
More specifically kills tumor cells Kills both normal and malignant cells to the same extent
Given in continuous infusion or frequent small doses Intermittent high dose therapy
G1 Asparginase, corticosteroids ALKYLATING AGENTS
S ANTIMETABOLITES ANTICANCER ANTIBODIES
ANTHRACYCLINS (doxorubicin, daunorubicin) PLATIMUM AMALOGS
HYDROXYUREA
G2 BLEOMYCIN
CAMPTOTHECINS (Irenotecan, topotecan)
EPIPODOPHYLLOTOXINS ( Etopside)
M VINCA ALKALOIDS
TAXANES
TOXICITIES
MYELOSUPPRESSION All except Asparginase, Vincristine, Bleomycin
CARDIOTOXIC Anthracyclins, arsenic trioxide
NEPHROTOXIC Platinum compounds (cisplatin>carboplatin>oxaliplatin)
PULMONARY FIBROSIS Bleomycin, Bsulfan, Carmustine
PERIPHERAL NEUROPATHY Oxaliplatin, vincristine
Taxans (stoking & glove type)
HAEMORRHAGIC CYSTITIS Cyclophosphamide, Ifosfamide
HAND FOOT SYNDROME 5FU, Capecitabine, Doxorubicin
CEREBELLAR ATAXIA Pyrimidine analogs like Cytrabine & 5FU
SIADH Cyclophosphamide, Vincristine
SECONDARY LEUKEMIA All alkylating agents & alkylating like agents (in 4-5 years)
Etopside(in 1-3 years)
STERLITY Alkylating agents
DISULFIRAM LIKE REACTION Procarbazine
CHOLINERGIC SYNDROME Irinitecan
RADIATION RECALL SYNDROME Anthracyclins
TOXIC AMELIORATION
TOXICITY MEASURES
Methotrexate Folinic acid
Alkalynization of urine (Mtz is weak acid &reabsorbed in acidic urine)
Hemorrhagic cystitis (cyclophosphamide, ifosfamide) MESNA ( 2 mercapto ethyl sulfonyl sodium) systemic
ACETYLCYSTEINE irrigation of bladder
High fluid intake
Frequent voiding
CINV (Cytotoxic drug induced nausea &vomiting ) Ondansetron (5HT3 Antagonist)
TUMOR LYSIS SYNDROME (hyperkalemia, prophylactic ALLOPURINOL (xanthine oxidase inhibitor)
hyperphosphatemia, hyperuricemia, hyperuricosuria, alternatively RASBURICASE (uricase)
hypocalcemia, acute renal failure) Aggressive hydration
High urine output
Alkalinization of urine not recommended/controvvertial
Diuresis is reserved for well hydrated patients
HEMODIALYSIS (if above fails)
MYELOSUPPRESSION SARGRAMOSTIM
Recombinant GM-CSF/G-CSF
BONE MARROW TRANSPLANT (for extreme suppression)
CANCER CACHEXIA THALIDOMIDE
CYTOPROTECTION of normal tissue AMIFOSTINE= WR-2721=prodrug
(active= free thiol=WR-1065, activation @normal tissue)
USES=cisplatin based chemotherapy & radiation therapy
Anthracyclin induced CARDIOTOXICITY DEXRAZOXANE (ICRF-187) Iron chelating agent
Cardio protective agent, derivative of EDTA
CLASSIFICATION
ALKYLATING AGENTS NITROGEN MUSTARD ACUTE TOXICITY DELAYED TOXICITY USES
(Alkylation of DNA at (1)MECHLORETHAMINE CINV-chemo induced nausea Myelosuppression (delayed type- MOPP-hodgkins lymphoma
N7 & O6 position of (First anticancer drug) vomiting (4hr-48hrs) onset=7d, Nadir=10-14d,
Guanine→DNA cross Myelosuppression recovery=21-28d)
linking b/n 2 Alopecia
strands→ prevents
duplication
AA are commonly (2)CYCLOPHOSPHAMIDE CINV Myelosuppression (CP>Ifo) Wagners granulomatosis DOC
used in chronic [CP→4hydroxyCP↔aldophosphamide Myelosuppression Alopecia, SIADH CMF-Breast, small cell lung ca
leukemia → Acrolein (toxic) & phosphamide (CP>Ifo) Hemorrhagic cystitis (Ifo>CP) Broad spectrum
mustard (active)] Sec cancer-transitional cell cancer of
bladder
AA are non phase (3)IFOSFAMIDE CINV Myelosuppression (CP>Ifo) Broad spectrum
specific 4hydroxy ifosfamide (active) Myelosuppression (CP>Ifo) Alopecia Lung, breast, ovary, sarcoma,
Hemorrhagic cystitis (Ifo>CP) testis, germ cell tumour
AA causes secondary (4)MELPHAN amino acid CINV Myelosuppression Multiple lyeloma DOC
leukemia in 4-5 years derivative of mechloretamine Myelosuppression No alopecia Can replace C in CMF
(5)CHLORAMBUCIL Myelosuppression Myelosuppression CLL, Hodgkins
CINV is rare No alopecia
NITROSOUREAS Nitrosoureas causes delayed
(lipophilic-crosses BBB) Myelosuppression (onset-15d,
Nadir-4wks, recovery-6wks)
(1)CARMUSTINE (BCNU- bis chloro CINV (severe-2hrs) Myelosuppression, male infertility, Brain tumors DOC
nitroso urea) Pulmonary fibrosis (Glioblastoma multiforme,
astrocytoma,medulloblastoma)
(2)LOMUSTINE (CCNU) CINV (severe-2hrs) Myelosuppression do
Interstitial lung disease
(3)SEMUSTINE (methyl CCNU) CINV (severe-2hrs) myelosuppression do
(4)STREPTOZOCIN (methylation of CINV (severe-2hrs) No myelosuppression Pancreatic islet cell tumour
protein & nucleic acid) Carcinoid tumour
ALKYL SULFONATES (Intra strand cross
linking of DNA by 2 N7 Guanine)
BUSULFAN (Dealkylating agent) Hyperuricemia (MC) Sterlity, gynecomastia, seizures, Skin CML-DOC until imatinib
pigmentation, Adrenal insufficiency Conditioning of BM transplant
Pulmonary fibrosis (specific)
ETHYL ENIMINES
THIOTEPA (Organophosphorous) CINV myelosuppression Seldom used now
NON CLASSICAL TRIAZENES
ALKYLATING AGENTS
Acts on RNA &Protein DACARBAZINE (Active-methyl CINV-severe Permanent sterility MAID-sarcoma, ABVD-hodgkins
synthesis not/mild carbonium ion) Myelosuppression (early/classical) Malignant melanoma (most
DNA active agent)
PROCARBAZINE (autoxidize CINV, MAO inhibitor Myelosuppression, Dermatitis MOPP-hodgkins
spontaneously, Active-Azoprocarbazine, Disulfiram like reaction Leukenogenic, teratogenic PCV-glioblastoma
crosses BBB)
ALTRETAMINE CINV-severe Neurotoxic Refractory ovarian cancer
Hypotension Nephrotoxic
ALKYLATING LIKE PLATINUM COMPOUNDS
AGENTS
1ST gen platinum CISPLATIN CINV (most emitogenic) Myelosuppression CMF-Solid malignancies
Inactivated by Hypo Mg, K, Ca sec to hypo Nephrotoxicity,Ototoxicity
aluminum Mg) Secondary leukemia
2nd generation CARBOPLATIN CINV (cis>carbo) Myelosuppression (carbo>cis) Less potent than cisplatin (1:4)
platinum, Cross No nephrotoxicity GemCarco-lung cancer
resistance-cisplatin
3rd generation OXALIPLATIN PSN pathy (reversible hand & Neurotoxicity (dose limiting) FOLFOX- colon cancer
platinum foot, temp loss) No nephrotoxicity Cis/carboplatin resistance
No cross resistance PSN pathy(irreversible, hand, foot,
leg, arm, temp loss, propio loss)
ANTIMETABOLITES FOLATE ANTAGONISTS
S phase specific METHOTREXATE Hepatotoxicity Choriocarcinoma DOC
Myelosuppression ALL, Osteosarcoma, RA, ectopic
Mucositis Myasthenia, psoriasis, meningeal
leukemia (intrathecal route)
Inhibits DNA synthesis PEMETREXED Mesothelioma, non small cell
lung
No acute toxicities PURINE ANALOGUE
Commonly used in 6 THIO GUANINE Myelosuppression Adult acute leukemia
acute leukemias Hepatotoxicity
6 MERCAPTO PURIME Myelosuppression, hepatotoxicity Childhood acute leukemia
FLUDRABINE Myelosuppression, Flu like symptom
(fever, myalgia,arthralgia)
CLADRIBINE Myelosuppression, Hairy cell leukemia
Nephrotoxic, CINV
PENTOSTATIN Nephrotoxic Hairy cell leukemia
PYRIMIDINE ANALOGUE
5 FLUOROURACIL (5FU) GI upset-diarrhoea (MC)
Hand foot syndrome, CINV
Myelosuppression, neurotoxicity
Cerebellar ataxia
CYTRABINE Stomatitis, CINV, Cerebellar ataxia AML
myelosuppression
CAPECITABINE CINV,Diarrhoea, Metastatic breast cancer
Hand foot syndrome Metastatic colorectal cancer
Myelosuppression (<5FU)
GAMECITABINE CINV, Myelosuppression (dose Pancreatic cancer DOC
limiting) Bladder & Non small cell lung Ca
ANTIBIOTICS ANTHRACYCLINS Topoisomerase 2 inhibitor Quione Free radical injury & Membrane binding (responsible
(mc) intercalation b/n DNA strands for cardiotoxicity)
DOXORUBICIN (ADRIAMYCIN) CINV, Alopecia Myelosuppression (dose limiting, Broad spectrum
neutropenia>thrombocytopenia) Solid tumors & sarcomas
Cardiotoxicity(cardiomyopathy,CHF) (rhabdo/ leiomyosarcoma,
Radiation recall Kaposi sarcoma)
Hand foot syndrome
DAUNORUBICIN CINV, Alopecia Myelosuppression, cardiotoxicity, Narrow spectrum
radiation recall AML
IDARUBICIN (synthetic Daunorubicin CINV, Alopecia, Red Myelosuppression, cardiotoxicity, AML (more efficacious than
analogue) urine(not hematuria) radiation recall daunorubicin)
MITOXANTRONE CINV, Bluish discoloration of Myelosuppression (dose limiting)
nails Lower cardiotoxicity
OTHER ANTIBIOTICS
BLEOMYCIN Allergic reaction Pulmonary fibrosis (dose limiting) HL, NHL, SCC
(Glyco peptide Antibiotic) Hypotension Mucocutaneous toxicity Malignant pleural effusion
Free radical injury→ds-ss DNA breaks, Marrow sparing Ascitis (sclerosing agent)
have both DNA & Fe binding domain
MITOMYCIN- C CINV Hemolytic uremic syndrome Radiosensitizer-DOC
Acts as alkylating agent Pulmonary fibrosis SCC
8th nerve damage
DACTINOMYCIN CINV Myelosuppression Pediatric tumors (Ewing’s,
Inhibits all forms of DNA dependent RNA Alopecia wilm’s, Rhabdomyosarcoma)
synthesis, r-RNA most sensitive Radiation recall Radiosensitizer
ACTINOMYCIN CINV Myelosuppression Pediatric tumors (Ewing’s,
Desquamation Alopecia wilm’s, Rhabdomyosarcoma)
Radiosensitizer
PLICAMYCIN CINV
ENZYME L-ASPARGINASE (inhibits protein Anaphylaxis/hypersensitivity- Hypercoagulable state ALL
synthesis of tumor cell by depletion of L- fever,chills,rash,uticaria Pancreatitis, Hepatotoxicity Ineffective in solid tumors
Aspargine) (brobchospasm,hypotension Marrow sparing, no alopecia (normal cells spared)
if severe)
PLANT DERIVED VINCA ALKALOIDS M phase specific Inhibits tubulin polymerization Mitotic inhibitors
VINCRISTINE Alopecia PSNpathy Lymphosarcoma, wilm’s, Ewing’s
SIADH, Marrow sparing Remission of childhood acute
leukemia.
VINBLASTINE Alopecia (Vc>Vb) PSNpathy (Vc>Vb) Hodgkin’s, testicular carcinoma
Myelosuppression
EPIPODOPHYLOTOXINS Topoisomerase 2 inhibitor
ETOPSIDE (VP-16) CINV, Hypotension Myelosuppression, early onset
secondary leukemia (1-3 years)
alopecia
TENIPOSIDE (VP-26)
TAXANS M phase specific Enhance tubulin polymerization Spindle poison
PACLITAXEL Hypersensitivity PSNpathy (stocking glove type) Cisplatin resistance
Myelosuppression , Relapse &resistant breast/ovary
ca
DOCETAXEL (more potent) Hypersensitivity Myelosuppression, PSNpathy (is less Cisplatin resistance,
frequent) Relapse-resistant br/ovary ca
CAMPTOTHECIN Topoisomerase 1 inhibitor ss DNA breaks
TOPOTHECAN CINV Myelosuppression (dose limiting)
IRINOTHECAN (active= SN-38) CINV, Cholinergic syndrome Myelosuppression, cholinergic Advanced colorectal ca- DOC
(SLUDGE) including early syndrome (SLUDGE) including late
diarrhea-24hrs diarrhea 3-10d (dose limiting)
MISCELLANIOUS ARSENIC TRIOXIDE (degradation of PMLI Headache, light headedness Cardiotoxic (QT prolongation, APL-induction in tretinoin
& RARα protein) CINV arrhythmias), myelosuppression relapse and refractory
Syndrome-fever, fluid retention, wt
gain, rash
Hydroxyurea has HYDROXYUREA (inhibits ribonucleotide CINV Myelosuppression (dose limiting) CML
100% oral reductase→inhibits DNA synthesis) Hyperpigmentation AML-blast crisis
bioavailability
IMATINIB (Bcr-Abl Tyrosine kinase CINV Fluid retention, Ankle & perioral CML-chronic phase
inhibitor) edema GIST with Ckit tyrosine kinase
DASATINIB & NILOTINIB (novel agents- CML- imatinib
TK inhibitors) resistance/intolerance
SPECIFIC CHEMOTHERAPY REGIMENS
(1) AML (All subtypes except M3)
INDUCTION CHEMOTHERAPY: With cytarabine (ara-C) and an anthracycline (such as daunorubicin or idarubicin).[32] This induction chemotherapy regimen is
known as "7+3" (or "3+7"), because the cytarabine is given as a continuous IV infusion for seven consecutive days while the anthracycline is given for three
consecutive days as an IV push
The goal of the induction phase is to reach a complete remission. Complete remission does not mean that the disease has been cured; rather, it signifies that no
disease can be detected with available diagnostic methods
CONSOLIDATION THERAPY: Even after complete remission is achieved, leukemic cells likely remain in numbers too small to be detected with current diagnostic
techniques. If no further post remission or consolidation therapy is given, almost all patients will eventually relapse. Therefore, more therapy is necessary to
eliminate non-detectable disease and prevent relapse that is, to achieve a cure. The specific type of post remission therapy is individualized based on a patient's
prognostic factors and general health.
Good prognosis inv(16), t(8;21), and t(15;17) 3-5 course of consolidation chemotherapy
Intermediate risk normal cytogenetics or cytogenetic changes not falling Depends on specific situation like age, health, suitable donor
into good-risk or high-risk groups
High risk with high-risk cytogenetics, underlying MDS, or If suitable donor is available Allogenic stem cell transplant
therapy-related AML If donor is not available Consolidation chemo followed by Immunotherapy with a
combination of histamine dihydrochloride (Ceplene) and
interleukin-2 (Proleukin)
(2) M3 SUBTYPE AML (ACUTE PROMYELOCYTIC LEUKEMIA):
ATRA (all-trans-retinoic acid) in addition to induction chemotherapy
(3) RELAPSED AML:
If no further post remission or consolidation therapy is given, almost all patients will eventually relapse.
For patients with relapsed AML, the only proven potentially curative therapy is a stem cell transplant, if one has not already been performed.
A newer drug, gemtuzumab ozogamicin, which combines an antibody with a chemotherapy drug as an attempt to specifically "target" the leukemia cells, is effective
in some people after relapse has occurred.
Arsenic trioxide is used in relapsed cases of acute promyelocytic leukemia.
(4) ALL
INDUCTION CHEMOTHERAPY: Combination of Prednisolone or dexamethasone, vincristine, asparaginase (better tolerance in pediatric patients), and daunorubicin
(used in Adult ALL) is used to induce remission
CONSOLIDATION/INTENSIFICATION: vincristine, cyclophosphamide, cytarabine, daunorubicin, etoposide, thioguanine or mercaptopurine given as blocks in
different combinations. For CNS protection, intrathecal methotrexate or cytarabine is usually used combined with or without cranio-spinal irradiation
MAINTENANCE: daily oral mercaptopurine, once weekly oral methotrexate, once monthly 5-day course of intravenous vincristine and oral corticosteroids are
usually used.
(5) CML:
(6) CLL: Generally considered incurable. Combinations of fludarabine with alkylating agents (cyclophosphamide) produce higher response rates and a longer progression-
free survival than single agents:
* FC (fludarabine with cyclophosphamide)
* FR (fludarabine with rituximab)
* FCR (fludarabine, cyclophosphamide, and rituximab)
(7) REFRACTORY CLL: In this case more aggressive therapies, including lenalidomide (thalidomide derivative), flavopiridol (cyclin dependent kinase inhibitor), and
bone marrow (stem cell) transplantation, are considered. The monoclonal antibody, alemtuzumab (directed against CD52), may be used in patients with refractory,
bone marrow-based disease.
