A PHASE-I AND CLINICAL-PHARMACOLOGY STUDY OF INTRAVENOUSLY ADMINISTERED CARMINOMYCIN IN CANCER-PATIENTS IN THE UNITED-STATES

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (7) , 2944-2948
Abstract
Carminomycin (CMN) was administered i.v. to 44 patients with a variety of nonhematological cancers ever 4 wk at doses of 15, 20, 22.5 and 25 mg/m2. Granulocytopenia was the dose-limiting toxicity. The median granulocyte count for previously untreated patients receiving 22.5 mg/m2 was 0.962 cells/.mu.l, and for previously treated patients receiving 20 mg/m2 it was 0.420 cell/.mu.l. Moderate to severe phlebitis was associated with drug administration in 50% of cases. Nausea, vomiting and alopecia were mild. Three of 9 patients who received a total CMN dose of .gtoreq. 100 mg/m2 (mean, 132 mg/m2) developed unexplained decreases in radionuclide cardiac ejection fraction, with 1 patient developing decreased QRS amplitude and congestive heart failure at a total dose of 160 mg/m2. CMN is rapidly metabolized to carminomycinol. The elimination half-lives of CMN and carminomycinol are 6-10 and 50 h, respectively. CMN was a more potent inhibitor of human granulocyte-macrophage colony-forming units than was carminomycinol. Objective partial responses were seen in 2 of 7 previously untreated patients with non-small cell lung cancer and 1 of 3 patients with squamous cell carcinoma of the head and neck previously untreated with chemotherapy.