Term
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Definition
Mechanims: produce strong electrophiles and form covalent DNA linkages resulting in DNA damage. Cell cycle non-specific.
Classes: Nitrogen Mustards, Nitrosoureas, Triazenes, Platinum Analogs
Toxicity: Bone Marrow Toxicity (neutropenia, thrombocytopenia, anemia), Mucosal Toxicity (ulceration of mouth, intestines), N/V, Amenorrhea/Sterility, Risk of Leukemia
Resistance: decreased permeability/uptake, increased metabolism, enhanced DNA repair, increased glutathione production (inactivates alkylating agents) |
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Term
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Definition
ALKYLATING AGENT (Nitrogen Mustard)
Converted to active metabolite spontaneously in body fluids or actively in liver
Used in Hodgkin's Disease (MOPP), topically for cutaneous T-cell lymphoma
Toxicity: N/V, Myelosuppression |
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Term
Cyclophosphamide
Ifosfamide |
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Definition
ALKYLATING AGENT (Nitrogen Mustard)
Prodrugs; activated in liver (p450)
Taken PO with long half life
Cyclophosphamide: ALL, CLL, non-Hodgkin's lymphoma, breast/ovarian/lung cancer
Ifosfamide: sarcoma, testicular cancer
Toxicity: N/V, hemorrhagic cystitis (due to acrolein; treat with hydration and MESNA) |
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Term
Carmustine
Lomustine
Streptozocin |
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Definition
ALKYLATING AGENT (Nitrosoureas)
Carmustine & Lomustine: highly lipophilic, cross BBB and can treat brain cancer
Streptozocin: pancreatic islet cell carcinoma, carcinoid tumors
Toxicity: myelosuppression, N/V, renal, pulmonary fibrosis |
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Term
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Definition
ALKYLATING AGENT (Triazene)
Dacarbazine: prodrug requiring activation by hepatic cytochromes; given IV; part of AVBD to treat Hodgkin's lymphoma; also treats malignant melanoma
Temozolomide: converted to active form at physiologic pH; PO - good oral bioavailability; treats malignant gliomas
Toxicity: myelosuppression, N/V, flu-like symptoms |
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Term
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Definition
ALKYLATING AGENT (Platinum Analog)
Effective against testicular, ovarian, cervical, bladder carcinomas, head/neck cancer and lung cancer. Good for combination therapy.
Toxicity: nephrotoxicity, ototoxicity, N/V, peripheral motor/sensory neuropathy, mild myelosuppression |
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Term
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Definition
ALKYLATING AGENT (Platinum Analog)
Carboplatin: Ovarian cancer; Toxicity - myelosuppression
Oxaliplatin: gastric and colorectal cancer; Toxicity - peripheral neuropathy (cold induced paresthesias), neutropenia |
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Definition
Inhibit enzymes required for purine, pyrimidine or DNA/RNA synthesis.
Cell cycle specific (S phase). |
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Definition
ANTIMETABOLITE
Folic Acid antagonist - inhibits DHFR (enzyme that converts dietary folate to THF form required for thymidine and purine biosynthesis).
Treats ALL, choriocarcinoma, Burkitt's Lymphoma (MOPP), Breast/Ovarian/Head/Neck/Bladder cancer, osteosarcoma. Cannot penetrate CNS - must be given intrathecally for meningeal leukemia/metastases.
Toxicity: Myelosuppression, GI toxicity, Renal and Hepatic toxicity, defective oogenesis or spermatogenesis.
Prevent toxicity by giving leucovorin (activated folic acid).
Resistance: increased DHFR, decreased affinity for DHFR, reduced drug uptake |
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Term
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Definition
ANTIMETABOLITE
Folate analog
Inhibits DHFR, TS
Active against colon cancer, mesothelioma, pancreatic and non-small cell lung cancer |
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Term
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Definition
ANTIMETABOLITE
Pyrimidine analog; prodrug to active 5-FdUMP; inhibits TS and RNA synthesis
Given IV due to extreme GI toxicity and rapid hepatic degradation
Toxicity: Anorexia, N/V, mucosal ulceration, stomatitis, diarrhea, thrombocytopenia, anemia, hand-food syndrome (dermopathy), NO MYELOSUPPRESSION |
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