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Miscellaneous Anticancer Drugs

  • Amsacrine: 

    • Hepatic metabolism

    • Mechanism of Action:

      • DNA intercalation: produces single-and double-strand breaks

      • Interaction with topoisomerase II-DNA complexes

    • Clinical Uses:

      • Anthracyclines- and cytarabine-resistant acute myelogenous leukemia

      • Advanced ovarian cancer

      • Lymphomas

    •  Adverse Effects:

      • Does-limiting hepatic toxicity

      • Cardiac arrest has been noted with amsacrine infusion

  • Asparaginase  (El-spar):

    • Mechanism of action: depletion of serum asparagine {forming aspartic acid and ammonia}

      • Decreased blood levels of asparagine and glutamine inhibit protein synthesis in those neoplastic cells that express decreased levels of asparagine synthase.

      • Most normal cells express sufficient levels of asparagine synthase to avoid toxicity.

  • Hydroxyurea:

    • Mechanism of action:

      • Inhibits ribonucleotide reductase; depletes deoxyribonucleoside triphosphate pools

      • Acts at S phase.

    • Clinical Uses:

      • Melanoma [secondary role]

      • Chronic myelogenous leukemia [secondary role]

    •  Adverse Effects:

      • Bone marrow suppression

      • Nausea

      • Vomiting

      • Diarrhea

  • Mitoxantrone (Novantrone):

    • Mechanism of action:

      • Induces DNA strand breaks

      • Inhibits RNA and DNA synthesis

    • Clinical Uses:

      • Refractory acute leukemia

      • Pediatric and adult acute myelogenous leukemia

      • Non-Hodgkin's lymphoma's

      • Breast cancer

    •  Adverse Effects:

      • Dose-limiting: leukopenia

      • Mild nausea

      • Vomiting

      • Stomatitis

      • Alopecia

      • Some cardiotoxicity {arrhythmias}

  • Mitotane  (Lysodren):

    •  Clinical Use:Single indication-- adrenal carcinoma

      • Reduces excessive steroid secretion

    • Adverse Effects:

      • Diarrhea

      • Mental depression

      • Skin eruption

      • Anorexia

      • Nausea

      • Somnolence

      • Dermatitis

  • Retinoic acid Derivatives:

    • Clinical Uses:

      • Remissions -- acute promyelocytic leukemia

      • 13-cis-Retinoic acid: chemopreventive -- second primary tumors in patients with hand and neck squamous cell carcinoma.

    •  Adverse Effects:

      • Skeletal effects

      • Hepatic effects

      • Teratogenic effects

      • Mucocutaneous effects

  • Bone Marrow Growth Factors (sargramostim and filgrastim):

    • Reduces neutropenic sepsis and other complications of chemotherapy

    • Filgrastim shortens neutropenic state following induction chemotherapy for acute nonlymphocytic leukemia.

  • Amifostine 

    • Cytoprotective from effects of chemotherapy

Salmon, S. E. and Sartorelli, A. C. Cancer Chemotherapy, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p. 881-911.

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