From Jen: Onc1 Flashcards
Drugs affecting nucleotide synthesis
Methotrexate
5-fluorouracil
(decrease thymidine synthesis)
6-mercaptopurine
(decrease purine synthesis)
Drugs affecting DNA
Alkylating agents:
Cisplatin
(Cross-link DNA)
Dactinomycin
Doxorubicin
(Intercalate DNA)
Etoposide
(inhibit topoisomerase II)
Drugs affecting cellular division
Vinca alkaloids (inhibit microtubule formation)
Paclitaxel (inhibit microtubule disassembly)
Methotrexate
MTX
MOA: S-phase specific antimetabolite; folic acid analog that inhibits DHF reductase resulting in decreased dTMP
Use: leukemias, lymphomas, choriocarcinoma, sarcoma, ectopic pregnancy, abortion, RA, psoriasis
Adverse: myelosuppresion (reversible with leucovorin), microvascular fatty change in liver, mucositis
5-fluorouracil
5-FU
MOA: S-phase specific antimetabolite. Pyrimidine analog activated to 5F-dUMP, which covalently complexes folic acid. The complex inhibits thymidylate synthase
synergistic with MTX
Use: Colon cancer, other solid tumors, basal cell carcinoma
Adverse: myelosuppression (irreversible), photosensitivity
Antidote: thymidine
6-mercaptopurine
MOA: blocks de novo purine synthesis; activated by HGPRTase
Use: leukemia, lymphoma (not CLL or hodgkin’s)
Toxicity: Bone marrow, GI, liver
metabolized by xanthine oxidase, thus increased toxicity with allopurinol
Cytarabine
Inhibits DNA polymerase
Use: AML, ALL, high grade non-Hodgkin lymphoma
Adverse: leukopenia, thrombocytopenia, megaloblastic anemia
Cyclophosphamide
Isofosfamide
MOA: alkylating agents; covalently link DNA at guanine N-7. Requires activation by liver
Use: non-Hodgkin lymphoma, breast and ovarian cancers
Toxicity: myelosuppression; hemorrhagic cystitis, which can be partially prevented by mesna
Nitrosoureas
Carmustine, lomuside, semustine, streptozocin
MOA: alkylate DNA, requires activation
Crosses BBB
Use: brain tumors, including glioblastoma
Toxicity: CNS (dizziness, ataxia)
Cisplatin
Carboplatin
Cross-link DNA
Use: testicular, bladder, ovarian and lung carcinomas
Toxicity: Nephrotoxicity and acoustic nerve damage
Busulfan
Alkylates DNA
Use: CML. Also used for ablating bone marrow in hematopoietic stem cell transplants
Toxicity: Pulmonary fibrosis, hyperpigmentation
Doxorubicin (adraimycin),
Daunorubicin
MOA: generates free radicals and non-covalently intercalate in DNA (creating breaks in DNA strand to decrease replication)
Dactinomycin
actinomycin D
Intercalates in DNA
Use: Wilms tumor, Ewing’s sarcoma, rhabdomyosarcoma
childhood tumors
Toxicity: myelosuppression
Bleomycin
MOA: induces formation of free radicals, which cause breaks in DNA strands
Use: testicular cancer, Hodgkin’s lymphoma (part of ABVD regimen)
Toxicity: pulmonary fibrosis, skin changes, but minimal myelosuppression
Hydroxyurea
MOA: inhibits ribonucleotide reductase: ↓ DNA synthesis (S-phase specific)
Use: melanoma, CML, sickle cell disease (↑ HbF)
Toxicity: bone marrow suppression, GI upset
Etoposide
VP-16
MOA: G2 phase specific agent that inhibits topoisomerase II and ↑ DNA degradation
Use: small cell carcinoma of the lung and prostate, testicular carcinoma
Toxicity: myelosuppression, GI irritation, alopecia
Prednisone
May trigger apoptosis, even in non-dividing cells
Use: most commonly for glucocorticoid in cancer chemotherapy, CLL, Hodgkin’s lymphomas (part of MOPP regimen), autoimmune diseases
Toxicity: Cushing syndrome, immunosuppression, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis
Tamoxifen
Raloxifene
SERMs: receptor antagonists in breast, agonists in bone; block the binding of estrogen to estrogen receptor-positive cells
Use: breast cancer, may be helpful in osteoporosis prevention
Toxicity: ↑ risk endometrial carcinoma via partial agonist effects (tamoxifen only), hot flashes
Trastuzumab
herceptin
Monoclonal Ab against HER-2 (erb-B2). Helps kill breast cancer cells that overexpress HER-2, possibly through antibody dependent cytotoxicity
Use: metastatic breast cancer
Toxicity: cardiotoxicity
Imatinib
gleevec
Philadelphia chromosome bcr-abl tyrosine kinase inhibitor
Use: CML, GI stromal tumors
Toxicity: fluid retention
Vincristine
Vinblastine
MOA: M-phase specific alkaloids that bind to tubulin and block polymerization of microtubules so that mitotic spindle cannot form
Use: part of MOPP regimen (oncovin=vincristine) for Hodgkin’s lymphoma, Wilms’ tumor, choriocarcinoma
Toxicity:
Vincristine: neurotoxicity (areflexia, peripheral neuritis, paralytic ileus)
Vinblastine: bone marrow suppression (BLASTS)
Paclitaxel
other -taxols
MOA: M-phase specific agents that bind to tubulin and hyperstabilize polymerized microtubules so that mitotic spindle cannot break down
Use: ovarian and breast cancer
Toxicity: myelosuppression, hypersensitivity
