"Low-Dose Combination Chemotherapy of Disseminated Human Neoplasms"
Bruce L. Allen and John H. Frenster
Division of Oncology, Department of Medicine,
Stanford University School of Medicine
Stanford, California 94305, U.S.A.
The observations of Dr. Halterman and Dr. Leventhal (Sept. 25, p. 704), suggesting that chemotherapy and the immune apparatus of the host may be acting synergistically in leukemic patients, receive further support from our clinical work employing low doses of three-drug combination chemotherapy in patients with disseminated solid neoplasms of diverse types. Each patient was treated with low-dose C.O.F. chemotherapy--- 'Cytoxan' (cyclophosphamide) 1 mg. per kg. per day orally; 'Oncovin' (vincristine) 0.015 mg. per kg. per week intravenously; and 5-fluorouracil 10 mg. per kg. per week intravenously--- with only mild nausea and vomiting as toxic effects. Of the first five patients who received continuous therapy for at least one month, three patients (with pleural mesothelioma, osteogenic sarcoma, and cervical squamous-cell carcinoma) displayed a greater than 50% reduction in the size of evident pulmonary nodules, while the remaining two patients (with primary hepatoma and hypernephroma) displayed a significant slowing of evident tumour growth.
The tumour regressions observed in these patients with disseminated neoplasms of types usually resistant to conventional chemotherapy (1) suggest that the immune reactions against neoplastic cells may be less suppressed at low dose-levels of C.O.F. chemotherapy than at higher dose-levels of these same three drugs (1), allowing more effective expression of lymphocyte immunity (2) against neoplastic cell growth in vivo. In addition, since no significant depression of peripheral-blood lymphocyte counts was observed, it has become possible to add concurrent lymphocyte immunotherapy (3) while patients are receiving low-dose C.O.F. chemotherapy.
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3. Electron Microscopy of Human Lymphocytes with and without Activation by PHA (Busch H, 1974).
4. Frenster JH, Rogoway WM, "In-Vitro Activation and Reinfusion of Autologous Human Lymphocytes", Lancet vol.2; 979-980 (Nov. 2, 1968).
5. Frenster JH, Rogoway WM, "Immunotherapy of Human Neoplasms with Autologous Lymphocytes Activated In-Vitro", in: "Proceedings of the Fifth Leukocyte Culture Conference, (Harris J, ed.), pp. 359-373 (1970), New York: Academic Press.
6. Frenster JH, "Phytohemagglutinin-Activated Autochthonous Lymphocytes for Systemic Immunotherapy of Human Neoplasms", Annals. N. Y. Acad. Sci. 277: 45-51 (1976).