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S phase specific
- Cytarabine
- 6-thioguanine
- 6-mercaptopurine
- 5-FU
- methotrexate
- Hydroxyurea
- Etoposide
-
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M phase
- vinblastine
- vincristine
- paclitaxel
-
G0 phase
- alkylating agents
- antitumor antibiotics
- nitrosoureas (lomustine, carmustine)
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Cyclophosphamide
- p450 mediated biotransformation of cyclophophamide to alkylating agent that attacks at guanine N7 (covalently X-link DNA) and acrolein (toxic form)
- Use: non-hodgkin, ovarian, breast and neuroblastoma
- Toxicity: myelosuppression, hemorrhagic cystitis from acrolein (mesna binds acrolein to protect the bladder, hydration also helps)
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Cisplatin, carboplatin
- cross-links DNA strands
- Testicular, ovarian, bladder, lung cancer
- Toxicity: nephrotoxicity (prevent with amifostine-free radical scavenger) and acoustic nerve damage.
-
Busulfan
- Alkylates DNA
- ablate patient's bone marrow before bone marrow tansplantation
- Toxicity: pulmonary fibrosis, hyperpigmentation
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Nitrosoureas (carmustine, lomustine, semustine, streptozocin)
- require bioactivation. cross BBB
- Brain tumors (glioblastoma multiforma)
- CNS toxicity (dizziness, ataxia)
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Procarbazine
- reactive agent that forms hydrogen peroxide, which generates free radicals that cause DNA strand scission
- Hodgkin's and non-Hodgkin's lymphoma and brain tumors
- Toxicity: myelosuppressant, leukemogenic (cause cancer)
-
Dactinomycin
used for childhood tumors (children ACT out)
- intercalates in DNA
- Wilms' tumor, Ewing's sarcoma, rhabdomyosarcoma,
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Doxorubicin, adriamycin, daunorubicin
- generates free radicals, noncovalently intercalate in DNA --> breaks in DNA --> dec replication
- Use: Hodgkin, melomas, sarcomas, solid tumors (breast, endometrial, lung and ovarian)
- Toxicity: BMS, delayed CHF (dexrazoxane is an iron-chelating agent preventing the formation of free radicals)
-
Etoposide, teniposide
- inhibits topoisomerase II --> inc DNA degradation
- small cell carcinoma of the lung and prostate, testicular carcinomas
-
Methotrexate
- folic acid analog that inhibits dihydrofolate reductase --> dec dTMP --> dec DNA and dec protein synthesis
- Use: cancer, abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis
- Toxicity: myelosuppression which is reversered by leucovorin (folinic acid); macrovesicular fatty change in liver, teratogenic
-
5- fluorouracil
- pyrimidine analog covalently complexes folic acid --> complex inhibits thymidylate synthase
- use: cancer, neck cancer-topical for basal cell cancer and keratoses
- Toxicity: photosensitivity
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Hydroxyurea
- inhibits ribonucleotide reductase --> dec DNA synthesis
- melanoma, CML, sickle cell disease
-
6-mercaptopurine
- Purine analog --> dec de novo purine synthesis
- activated by HGPRTase
- Leukemias, lymphomas (not CLL or Hodgkin's)
- Metabolized by xanthine oxidase thus inc toxicity w/ allopurinol
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Bleomycin
- complexes w/ Fe and O2 --> DNA strand scission by creating free radicals
- hodgkin, testicular, head, neck, skin cancer
- Toxicity: pneumonitis, pulmonary fibrosis
-
6-thioguanine
- Purine analog --> dec de novo purine synthesisactivated by HGPRTaseacute lymphoid Leukemias, lymphomas
- can by given w/ allopurinol
-
Vincristine, vinblastine
- alkaloids that bind to tubulin in M-phase and block polymerization of microtubules so that mitotic spindle can't form.
- hodgkin's lymphoma, wilms' tumor, choriocarcinoma, ALL
- Vincristine- neurotoxicity, paralytic ileus
- Vinblastine- bone marrow suppression
-
Paclitaxel
- hyperstablize polymerized microtubules in M-phase so that mitotic spindle can't break down
- Toxicity: hypersensitivity
-
Colchicine, vincas, paclitaxel
inhibit microtubule. stop cell cycle in M phase
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Prednisone
most commonly used glucocorticoid in cancer chemotherapy.
-
Aldesleukin (IL-2)
used to inc BM cells
-
Filgrastim
- granulocyte colony-stimulating factor
- recovery of bone marrow
-
Sargramostim
- granulocyte-macrophage colony-stimulating factor
- recovery of bone marrow
-
Tamoxifen, raloxifene
- SERMs- receptor antagonists in breast and agonists in bone. Block the binding of estrogen to estrogen receptor- positive cells
- Use: breast cancer. also used to prevent osteoporosis
- Toxicity: Tamoxifen- inc risk of endometrial carcinoma
- Raloxifene- no inc in endometrial carcinoma
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Imatinib
- Philadelphia chromosome bcr-abl tyrosine kinase inhibitor
- Toxicity: fluid retention
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