H. Hansen, O. Selawry, F. Muggia
Mar 1, 1971
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Influential Citations
100
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Quality indicators
Journal
Cancer research
Abstract
Summary The clinical tolerance to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was explored in patients with advanced cancer. This compound is related to 1,3-bis(2-chloroethyl)-1-nitrosourea, an agent of recognized antineoplastic effectiveness, but has only one chloroethyl group, is more lipid soluble, and is at least as active or more active against mouse Leukemia 1210. A single p.o. dose of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was given because of the superiority of widely spaced doses against Leukemia 1210 and the expected delayed hematological toxicity. The starting dose of 15 mg/sq m body surface area corresponded to one-third of the minimal toxic dose in the most sensitive animal species in preclinical studies. Large initial increments of drug dose at presumably nontoxic levels were followed by progressively smaller dose increments to the range of moderate, reversible toxicity. Forty patients with cancer received 82 treatments. Reproducible subtoxic decrease of thrombocytes occurred at the third dose step (50 mg/sq m); decrease of leukocytes occurred at the fifth dose step (100 mg/sq m). Dose-limiting toxicity resulting in delayed thrombocytopenia and leukopenia within 4 and 6 weeks, respectively, was reached at 130 mg/sq m. This dose was well tolerated in 6 patients when given at intervals of 6 weeks. Objective responses at toxic doses were seen in 2 of 5 patients with evaluable bronchogenic carcinoma and in both patients with malignant lymphoma. Marked neurological improvement was noted in all 3 patients with glioblastoma multiforme.