Radiation Oncology/Chemotherapy

This is a brief listing of chemotherapy drugs that may be useful for the radiation oncologist to know. It is not to be an in depth discussion of how these drugs work, but it may touch on their basic type of action (i.e. nucleoside analogues). PharmGKB Chemotherapy combinations Alkylating Agents Nitrogen mustard analogues Cyclophosphamide Chlorambucil Melphalan Chlormethine Ifosfamide Trofosfamide Prednimustine Alkyl sulfonates Busulfan Treosulfan Mannosulfan Ethylene imines Thiotepa Triaziquone Carboquone Nitrosoureas Carmustine Lomustine Semustine Streptozocin Fotemustine Nimustine Ranimustine Epoxides Etoglucid Other alkylating agents Mitobronitol Pipobroman Temozolomide Dacarbazine Antimetabolites Folic acid analogues Methotrexate Raltitrexed pemetrexed (Alimta) Multitarget agent, inhibits several folate-dependent enzymes. Indication:pleural mesothelioma (combined with cisplatin), second line NSCLC Purine analogues Mercaptopurine Tioguanine Cladribine Fludarabine Clofarabine Pyrimidine analogues Cytarabine fluorouracil (generic 5-FU, Adrucil, Carac, Efudex, Fluoroplex, Fluorouracil) Pyrimidine analogue. Prodrug. Requires activation by thymidine phosphorylase (TP) to yield 5-FUdR then by thymidine kinase (TK) to form the active product to fluorodeoxyuridine monophosphate (FdUMP). 5-FdUMP forms a stable complex with thymidylate synthase resulting in disruption of DNA synthesis. Also incorporated into RNA and causes RNA disruption. Toxicity: myelosuppression, N/V, stomatitis, diarrhea, hand-foot syndrome. Coronary vasospasm Tegafur Carmofur Gemcitabine capecitabine (Xeloda) Oral. Mimics continuous infusion of 5-FU. Prodrug. Undergoes transformation in live by carboxylesterase then cytidine deaminase then thymidine phosphorylase (TP) which converts it to 5-FU. Toxicity: Compared to 5-FU, lower diarrhea, stomatitis, N/V, neutropenia; more hand-foot syndrome and hyperbilirubinemia. Leucovorin (Enhancer) Supplements intracellular folate supply, resulting in inhibition of thymidylate synthesis (TS) Antibiotics Anthracyclines Antitumor antibiotics, produced by Streptomyces soil fungus Mechanism: Intercalate between DNA base pairs and prevent DNA replication Toxicity: cardiac (arrhythmias, CHF) doxorubicin (Adriamycin, Rubex) Indications: ALL, AML, CLL, breast CA, gastric CA, SCLC, NSCLC, epithelial and germ cell ovarian CA, thyroid CA, neuroblastoma, Wilms' tumor, transitional bladder cell CA, cervical CA, endometrial CA, squamous cell carcinoma of the head and neck, primary hepatocellular CA, pancreatic carcinoma, hepatoblastoma, thymoma, gestational trophoblastic tumors, prostate CA, Hodgkin's disease, NHL, sarcoma, multiple myeloma, adrenocortical CA, carcinoid tumors, advanced esophageal CA, retinoblastoma daunorubicin (Cerubidine) Indications: ALL, AML, CML, Wilm's tumor, neuroblastoma, NHL epirubicin (Ellence, Pharmorubicin) Indications: node+positive breast CA, metastatic breast CA, esophageal/GEJ CA, locally unresectable and metastatic gastrica CA, advanced NSCLC, limited and extensive stage SCLC, Stage III-IV ovarian CA, Hodgkin's disease, NHL, soft-tissue sarcoma idarubicin (Idamycin) Indications: adult AML mitoxantrone (Novantrone, generic) Indications: hormone-refractory prostate CA, locally advanced and metastatic breast CA, adult AML, recurrent adult ALL, NHL. Also multiple sclerosis Other Antibiotics mitomycin-C (Mitomycin; Mutamycin) Mechanism: cross-links DNA Indications: gastric CA, esophageal CA, pancreatic CA, biliary CA, colorectal CA, anal CA, breast CA, H&N CA, NSCLC, cervical CA, bladder CA, CML Toxicity: delayed bone marrow suppression, pulmonary fibrosis bleomycin (Blenoxane) Mechanism: unknown but may involve binding to DNA, inducing lability of the DNA structure, and reduced synthesis of DNA Indications: Squamous H&N CA, esophageal CA, thyroid CA, cervical CA, penile CA, vulvar CA, testicular CA, HL, NHL, Kaposi's sarcoma, osteosarcoma, malignant pleural/pericardial/peritoneal effusion, melanoma, ovarian CA, gestational trophoblastic tumors, mycosis fungoides, verruca vulgaris plicamycin (Mithracin) Mechanism: complexes with DNA in the presence of divalent cations, thus preventing synthesis Indications: testicular CA Other indications: hypercalcemia and hypercalciuria associated with neoplasm, Paget's disease Alkaloids/Natural products Vinca alkaloids Vinblastine Vincristine Vindesine Vinorelbine Podophyllotoxin derivatives Etoposide Teniposide Colchicine derivatives Demecolcine Taxanes Paclitaxel (Taxol) Abraxane (ABI-007) - albumin-bound nanoparticle paclitaxel. Possibly less neurotoxicity. Docetaxel (Taxotere) Other Trabectedin Platinum drugs Cross-link DNA, block transcription and replication Cisplatin (IV) Toxicity: Ototoxicity Carboplatin (IV) Oxaliplatin (IV) Toxicity: Peripheral neuropathy. no nephrotoxicty. Moderate hematologic toxicity Topoisomerase I inhibitors irinotecan (Camptosar) Derivative of natural alkaloid camptothecin. Indications: metastatic CRC Toxicity: delayed diarrhea, myelosuppression. topotecan (Hycamtin) Indications: metastatic ovarian CA, SCLC, NSCLC, myelodysplastic syndrome, CML Monoclonal Antibodies Edrecolomab Rituximab Trastuzumab alemtuzumab (Campath) Indications: B-CLL, second line Gemtuzumab cetuximab (Erbitux) (IV) Anti-EGFR (HER-1, c-ERB-1) Toxicty: acneiform rash (face and trunk). Should limit sun exposure. bevacizumab (Avastin) Binds and neutralizes VEGF pertuzumab, 2C4, (Omnitarg) HER2 dimerization inhibitor Use in prostate cancer panitumumab (Vectibix) Fully human Anti-EGFR (IV) Colon ca. Small molecule agents Bortezomib (Velcade) - inhibits proteasome / ubiquitin pathway. Inhibits NFKB (nuclear factor κ-B), several cytokines, VEGF, fibroblast growth factor Multiple myeloma Thalidomide - immunomodulator. Multiple myeloma Lenalidomide - analog of thalidomide Multiple myeloma Imatinib (Gleevec), STI-571 - tyrosine kinase inhibitor of ABL, BCR-ABL, KIT, PDGF receptor. Targets ABL tyrosine kinase which is activated by BCR-ABL translocation (i.e. Philadelphia chromosome). CML (BCR-ABL), GIST (KIT/c-kit), Dermatofibrosarcoma protuberans (PDGF) Gefitinib (Iressa) - inhibits tyrosine kinase domain of EGFR non-small cell lung cancer FDA approved for: single drug therapy for refractory NSCLC Sunitinib (Sutent) - anti-angiogenesis Renal cell carcinoma Temsirolimus (CCI-779) - m-TOR inhibitor Renal cell carcinoma Lapatinib (Tykerb) - EGFR tyrosine kinase inhibitor Renal cell carcinoma, her-2-neu positive breast cancer Sorafenib (Nexavar) - anti-angiogenesis. Inhibits VEGF, Ras kinase, and PDGF. Dasatinib CML