Anticancer Drug

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Transcript of Anticancer Drug

CANCER CHEMOTHERAPY

ACRONYM OF REGIMENHodgkin's lymphoma (stage 3 & 4) ABVD BEACOPP MOPP Stanford V VAPEC-B CHOP m-BACOD MACOP-B COPP COP or CVP Adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine Bleomycin, etoposide, Adriamycin (doxorubicin), cyclophosphamide, Oncovin (vincristine), procarbazine, prednisone Mechlorethamine, Oncovin (vincristine), procarbazine, prednisone Doxorubicin, mechlorethamine, bleomycin, vinblastine, vincristine, etoposide, prednisone Vincristine, Adriamycin (doxorubicin), prednisone, etoposide, cyclophosphamide, bleomycin Cyclophosphamide, hydroxydoxorubicin (doxorubicin), vincristine (Oncovin), prednisone(TOC) Methotrexate, bleomycin, Adriamycin (doxorubicin), cyclophosphamide, Oncovin (vincristine), dexamethasone Methotrexate, leucovorin (folinic acid), Adriamycin (doxorubicin), cyclophosphamide, Oncovin (vincristine), prednisone, bleomycin Cyclophosphamide, Oncovin (vincristine), procarbazine, prednisone Cyclophosphamide, Oncovin (vincristine), prednisone

Non-Hodgkin lymphoma, CLL

Non-Hodgkin lymphoma in patients with history of cardiovascular disease B cell non-Hodgkin lymphoma

Lymphoma Aggressive lymphomas, progressive neuroblastoma High-risk progressive or recurrent lymphomas Breast cancer

CHOP-R or RCHOP R-FCM CBV EPOCH ICE ICE-R AC CA CAF CMF EC FEC FL (Aka- Mayo)

CHOP + rituximab Rituximab, fludarabine, cyclophosphamide, mitoxantrone Cyclophosphamide, BCNU (carmustine), VP-16 (etoposide) Etoposide, prednisone, Oncovin, cyclophosphamide, and hydroxydaunorubicin ifosfamide, carboplatin, etoposide (VP-16) ICE + rituximab Adriamycin (doxorubicin), cyclophosphamide Cyclophosphamide, Adriamycin (same as AC) Cyclophosphamide, Adriamycin , fluorouracil (5-FU) Cyclophosphamide, methotrexate, fluorouracil (5-FU) Epirubicin, cyclophosphamide Fluorouracil (5-FU), epirubicin, cyclophosphamide Fluorouracil (5-FU), leucovorin (folinic acid)

Colorectal cancer

Testicular cancer, germ cell tumors

FOLFOX FOLFIRI BEP EP VIP TIP Thal/Dex VAD PCV CAV VAC ECF MAID

Fluorouracil (5-FU), leucovorin (folinic acid), oxaliplatin Fluorouracil (5-FU), leucovorin (folinic acid), irinotecan Bleomycin, etoposide, platinum agent (cisplatin) Etoposide, platinum agent (cisplatin) Etoposide, ifosfamide, platinum agent cisplatin Paclitaxel, ifosfamide, platinum agent cisplatin Thalidomide, dexamethasone Vincristine, Adriamycin (doxorubicin), dexamethasone Procarbazine, CCNU (lomustine), vincristine Cyclophosphamide, Adriamycin (doxorubicin), vincristine Vincristine, Actinomycin, Cyclophosphamide Epirubicin, cisplatin, fluorouracil (5-FU) Mesna, Adriamycin (doxorubicin),ifosfamide, dacarbazine

Multiple myeloma Brain tumors Lung cancer Rhabdomyosarcoma Gastric cancer and oesophageal cancer Sarcoma

LOG KILL HYPOTHESISAccording 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

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EFFECT OF CELL CYCLECELL CYCLE SPECIFIC AGENTS (CCS) Kills cells in cell cycle Useful in High growth fraction tumors (hematological malignancies, Burkitt s lymphoma, trophoblastic choriocarcinoma) More specifically kills tumor cells Given in continuous infusion or fre uent small doses G1Asparginase, corticosteroids S ANTIMETABOLITES ANTHRACYCLINS (doxorubicin, daunorubicin) HYDROXYUREA G2BLEOMYCIN CAMPTOTHECINS (Irenotecan, topotecan) EPIPODOPHYLLOTOXINS ( Etopside) M VINCA ALKALOIDS TAXANES CELL CYCLE NONSPECIFIC AGENTS (CCNS) KILLS BOTH G0 and cycling cells (although cycling cells are more specific) Useful in both High growth fraction & low growth fraction tumors (solid tumors) Kills both normal and malignant cells to the same extent Intermittent high dose therapy ALKYLATING AGENTS ANTICANCER ANTIBODIES PLATIMUM AMALOGS

TOXICITIESMYELOSUPPRESSION CARDIOTOXIC NEPHROTOXIC PULMONARY FIBROSIS PERIPHERAL NEUROPATHY HAEMORRHAGIC CYSTITIS HAND FOOT SYNDROME CEREBELLAR ATAXIA SIADH SECONDARY LEUKEMIA STERLITY DISULFIRAM LIKE REACTION CHOLINERGIC SYNDROME RADIATION RECALL SYNDROME All except Asparginase, Vincristine, Bleomycin Anthracyclins, arsenic trioxide Platinum compounds (cisplatin>carboplatin>oxaliplatin) Bleomycin, Bsulfan, Carmustine Oxaliplatin, vincristine Taxans (stoking & glove type) Cyclophosphamide, Ifosfamide 5FU, Capecitabine, Doxorubicin Pyrimidine analogs like Cytrabine& 5FU Cyclophosphamide, Vincristine All alkylating agents & alkylating like agents (in 4-5 years) Etopside(in 1-3 years) Alkylating agents Procarbazine Irinitecan Anthracyclins

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TOXIC AMELIORATIONTOXICITY Methotrexate Hemorrhagic cystitis (cyclophosphamide, ifosfamide) MEASURES Folinic acid Alkalynization of urine (Mtz is weak acid &reabsorbed in acidic urine) MESNA ( 2 mercapto ethyl sulfonyl sodium) systemic ACETYLCYSTEINE irrigation of bladder High fluid intake Fre uent voiding Ondansetron (5HT3 Antagonist) prophylactic ALLOPURINOL (xanthine oxidase inhibitor) alternatively RASBURICASE (uricase) Aggressive hydration High urine output Alkalinization of urine not recommended/controvvertial Diuresis is reserved for well hydrated patients HEMODIALYSIS (if above fails) SARGRAMOSTIM Recombinant GM-CSF/G-CSF BONE MARROW TRANSPLANT (for extreme suppression) THALIDOMIDE AMIFOSTINE= WR-2721=prodrug (active= free thiol=WR-1065, activation @normal tissue) USES=cisplatin based chemotherapy & radiation therapy DEXRAZOXANE (ICRF-187) Iron chelating agent Cardio protective agent, derivative of EDTA$

CINV (Cytotoxic drug induced nausea &vomiting ) TUMOR LYSIS SYNDROME (hyperkalemia, hyperphosphatemia, hyperuricemia,hyperuricosuria, hypocalcemia, acute renal failure)

MYELOSUPPRESSION

CANCER CACHEXIA CYTOPROTECTION of normal tissue

Anthracyclin induced CARDIOTOXICITY

CLASSIFICATIONALKYLATING AGENTS (Alkylation of DNA at N7 & O6 position of Guanine DNA crosslinking b/n 2 strands prevents duplication AA are commonly used in chronic leukemia NITROGEN MUSTARD ACUTE TOXICITY DELAYED TOXICITY USES

(1)MECHLORETHAMINE (First anticancer drug)

CINV-chemo induced nausea Myelosuppression (delayed typevomiting (4hr-48hrs) onset=7d, Nadir=10-14d, Myelosuppression recovery=21-28d) Alopecia

MOPP-hodgkins lymphoma

(2)CYCLOPHOSPHAMIDE [CP 4hydroxyCP aldophosphamide Acrolei n (toxic) &phosphamide mustard (active)]

CINV Myelosuppression (CP>Ifo)

AA are non phase specific AA causes secondary leukemia in 4-5 years

(3)IFOSFAMIDE 4hydroxy ifosfamide (active) (4)MELPHANamino acid derivative of mechloretamine

CINV Myelosuppression(CP>Ifo) CINV Myelosuppression

Myelosuppression (CP>Ifo)Alopecia, SIADH Hemorrhagic cystitis (Ifo>CP) Sec cancer-transitional cell cancer of bladder Myelosuppression (CP>Ifo) Alopecia Hemorrhagic cystitis (Ifo>CP) Myelosuppression No alopecia

Wagnersgranulomatosis DOC CMF-Breast, small cell lung ca Broad spectrum

Broad spectrum Lung, breast, ovary, sarcoma, testis, germ cell tumour Multiple lyeloma DOC Can replace C in CMF

(5)CHLORAMBUCIL NITROSOUREAS (lipophilic-crosses BBB) (1)CARMUSTINE (BCNU- bischloronitroso urea)

Myelosuppression CINV is rare

CINV (severe-2hrs)

Myelosuppression No alopecia Nitrosoureas causes delayed Myelosuppression (onset-15d, Nadir-4wks, recovery-6wks) Myelosuppression, male infertility, Pulmonary fibrosis

CLL, Hodgkins

(2)LOMUSTINE (CCNU) (3)SEMUSTINE (methyl CCNU) (4)STREPTOZOCIN (methylation of protein & nucleic acid)

CINV (severe-2hrs) CINV (severe-2hrs) CINV (severe-2hrs)

Myelosuppression Interstitial lung disease myelosuppression No myelosuppression

Brain tumors DOC (Glioblastomamultiforme, astrocytoma,medulloblastoma ) do do Pancreatic islet cell tumour Carcinoid tumour

ALKYL SULFONATES(Intra strand cross linking of DNA by 2 N7 Guanine) BUSULFAN (Dealkylating agent)

Hyperuricemia (MC)

Sterlity, gynecomastia, seizures, Skin pigmentation, Adrenal insufficiency Pulmonary fibrosis (specific) myelosuppression

CML-DOC until imatinib Conditioning of BM transplant

NON CLASSICAL ALKYLATING AGENTS Acts on RNA &Protein synthesis not/mild DNA

ETHYL ENIMINES THIOTEPA (Organophosphorous) TRIAZENES

CINV

Seldom used now

DACARBAZINE (Active-methyl carbonium ion)

CINV-severe

Permanent sterility Myelosuppression (early/classical)

PROCARBAZINE (autoxidize spontaneously, Active-Azoprocarbazine, crosses BBB) ALTRETAMINE ALKYLATING LIKE AGENTS 1ST gen platinum Inactivated by aluminum 2nd generation platinum, Cross resistancecisplatin 3rd generation platinum No cross resistance ANTIMETABOLITE S S phase specific PLATINUM COMPOUNDS CISPLATIN

CINV, MAO inhibitor Disulfiram like reaction CINV-severe Hypotension

Myelosuppression, Dermatitis Leukenogenic, teratogenic Neurotoxic Nephrotoxic

MAID-sarcoma, ABVDhodgkins Malignant melanoma (most active agent) MOPP-hodgkins PCV-glioblastoma Refractory ovarian cancer

CARBOPLATIN

CINV (most emitogenic) Hypo Mg, K, Ca sec to hypo Mg) CINV (cis>carbo)

Myelosuppression Nephrotoxicity,Ototoxicity Secondary leukemia Myelosuppression (c