CYTOKINETIC CHEMOTHERAPY DESIGN FOR THE TREATMENT OF ADVANCED LUNG-CANCER

  • 1 January 1979
    • journal article
    • research article
    • Vol. 63  (5) , 767-773
Abstract
Patients (60) with lung cancer, 48 with extensive disease and 12 with regional disease, were treated with cyclophosphamide and methotrexate on a schedule based on cellular kinetics concepts. Initial therapy was with cyclophosphamide (1.1 g/m2 i.v.) followed by methotrexate (20 mg/m2 orally twice wk) beginning 9 days later when the tumor was considered to be most susceptible to an S-phase-specific drug. The overall objective response rate was 62% (25% complete responses and 37% partial responses) with an estimated median survival time (MST) of 46 wk. Seventeen of 19 patients with small cell carcinoma (89%) responded (10 complete responses and 7 partial responses). The MST was 62 wk. The last nine patients entered in the study with small cell carcinoma had an MST of 71 wk, reflecting additional responses to subsequent treatment. The objective response rate of large cell carcinoma (9 of 16 patients) and adenocarcinoma (10 of 18 patients) was 56%.The MST of patients with the former cell type was longer (57 wk) than that of patients with the latter cell type (34 wk). One of 7 patients with epidermoid carcinoma responded. The MST of patients with a complete response and those with regional disease were 70 and 63 wk, respectively. Patients with a performance status of 0 or 1 survived longer (MST, 56 wk) than those with a performance status of 2 or 3 (MST, 29 wk). The mean dose of cyclophosphamide per course was 1.275 g/m2 and the mean nadir leukocyte count per patient was 2890/mm3. The incidence per course of leukocytes < 1000/mm3 or platelets < 50,000/mm3 was < 3%. Mucositis was common. This schedule provides excellent maintenance therapy with undue toxicity. These survival time distributions compare favorably with those of previous reports, particularly for patients with small cell or large cell carcinoma, regional disease, or complete responses.

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