-Cell Cycle Non-Specific Drugs (CCNS)
-Delayed Toxicity: Occurs within *Days or Weeks.*
–Antimetabolites:*No acute toxicity.*
–*Antimitotics: acute and delayed toxicity.*
–Acute and chronic toxicity.
–Side effects more severe.*
-Cisplatin and other Metal Compounds
-New CCNS Drugs
-Will affect both non-cycling and cycling cells.
-acute and chronic toxicity
2. Alkyl Sufonatates (Busulfan)
3. Ethylenimines (Thiotepa)
4. Triazines (Decarbazine)
5. Tetrazines (Temozolomide)
6. Nitrosureas (Carmustine, Iomutsine, Streptozocin)
–nausea and vomiting
–cross-resistance occurs between many of these agents.
-Thiotepa: ovarian cancer.
-Carmustine: brain cancer.
–Mediated by drug *binding to DNA and topoisomerase II.*
-Can also generate *free radicals.*
-Cell exposure leads to *apoptosis*: we want this to happen.
-Severe local vesicant action can occur.
*-May impart a red color to urine.*
*-Cardiac toxicity: peculiar adverse event observed with these agents. Effects normal heart function.* (ask cardiologist if you can use this drug on a patient.)
-In contrast to daunorubicin, is active in a number of *solid tumors (breast cancer).*
-Severe local vesciant action can occur.
-*May impart a red color to urine.*
-*Erythematous streaking near site of infusion (Adriamyacin flare).*
-*Binds to topoisomerase II.
-Competitive antagonist to daunorubicin and doxorubicin.
-Contraindicated during cancer treatment with either drug.*
*-Blocks transcription of DNA by RNA polymerase.*
-Soft tissue sarcomas (Ewing’s and Kaposi’s).
-Also used to inhibit immunological responses (e.g. renal transplants).
-Reduction in bone marrow function.
-Loss of appetite.
-Others: dysphagia, rashes/acne, mouth sores, fever, diarrhea, temporarily altered liver function.
-Can cause oxidative damage to DNA leading to single- and double-stranded breaks in DNA.
-Can be used in combination therapy in squamous carcinomas of the head, neck and esophagus as well as in Hodgkin’s and non-Hodgkin’s lymphoma.
*-Significant cutaneous toxicity.
-Significant pulmonary toxicity.*
-*Toxicities do not overlap with other drugs.*
-Results in *renal, hearing and neurological toxicity.*
-Combination therapy with *bleomycin, etoposide, and vinblastine for advanced testicular cancer.*
-Less nausea, neurtoxicity, ototoxicity, and neurotoxicity.
-Dose limiting toxicity is myelosuppression primarily evident as thrombocytopenia.*
-Effective alternative for patients with responsive tumors who are *unable to tolerate cisplatin because of impaired renal function.*
-Approved for use in combination with paclitaxel or cylcophosphamide in patients with advanced ovarian cancer.
-Mechanism:*induces differentiation and apoptosis.*
-Side effects: *Lightheadedness during infusion, fatigue, musculoskeletal pain, hyperglycemia and peripheral neuropathy.*
-When bound to the ER, tamoxifen induces a change in the 3D shape of the receptor, inhibiting binding of the estrogen responsive element on DNA.
-Usually prescribed for 5 years (development of uterine tumors).
-Nausea and vomiting.
-Depression, tiredness and dizziness.*
-Antitumor effects are mediated by binding to a specific cytoplasmic receptor, which when activated, induces a program of gene expression that leads to *apoptosis.*
-Takes time, it is not instantaneous.
-Side effects: acute: can cause fever; chronic: can include mental depression (coma in extreme cases) and hepatotoxicity.
-Estrogen synthesis occurs in the ovary and the adrenal gland.
-After menopause, *synthesis only in the adrenal gland.*
-Non steroidal drugs which *inhibit aromatase.*
-Initially used only in patients who were *estrogen receptor negative (ER-).*
-*Starting to replace tamoxifen* in breast cancer treatment in many postmenopausal women independent of ER status.
-Toxicity not as great as tamoxifen and is as effective.
-Expression of this protein is associated with decreased survival due to more aggressive disease.
*-Mechanism of action: cell cycle arrest via anti-body mediated cytoxicity.*
-Used in Her2+ breast cancer patients in combination with Paclitaxel.
-Toxicity: *Diarrhea and hematologic effects are most common.*