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