• 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

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