John H. Frenster, M.D.,
Division of Oncology, Department of Medicine,
Stanford University, Stanford, California.
Because cancer chemotherapy agents can supress both neoplastic cells and the immune reactions directed against neoplastic cells (Cancer 28: 851 (1971), it has become necessary to consider whether the maximal drug dosage tolerated coincides with the optimal drug dosage desired for a given patient (Lancet 2: 1324 (1971).
Patients with disseminated neoplasms of unusual histology were treated with low-dose C.O.F. chemotherapy (cyclophosphamide, 1.0 mg/kg/day, p.o.; vincristine, 0.015 mg/kg/week, i.v.; and 5-fluorouracil, 10 mg/kg/week, i.v.) with only mild nausea, vomiting, or paresthesias as toxicity.
Of the first 32 patients treated, 22 received continuous therapy for at least 4 weeks, and of these, 14 displayed a reduction of more than 50% in the size of pulmonary nodules or palpable masses, 4 displayed a cessation of growth of these but no reduction in size, and 4 displayed continued growth of these tumor parameters. The patient longest in the series has now been treated continuously for over 14 months, with marked regression of her disease, little toxicity, and a performance status improved from an initial 20% to a current 95% of normal activity.
This phase 2 study of low-dose C.O.F. chemotherapy has revealed objective regressions of disseminated neoplasms in patients with pleural mesothelioma, osteogenic sarcoma, squamous cell carcinoma (5), primary hepatoma, malignant melanoma, synovial sarcoma, angiosarcoma (2), diffuse histiocytic lymphoma, and myosarcoma.
Supported in part by Research Grants CA-10174 and CA-13524 from the National Cancer Institute, by Research Grant IC-45 from the American Cancer Society, and by a Research Scholar Award from the Leukemia Society.
Additional References:
1. "Low-Dose Combination Chemotherapy of Disseminated Human Neoplasms", 1971.