Chemotherapy in combination with biomodulation: a 5-year experience with cyclophosphamide and interleukin-2

There are four classical forms of immunotherapy: active, adoptive, restorative, and passive, and perhaps a fifth form, cytomodulatory, the upregulation of tumor-associated and HLA antigens to make tumors more recognizable by the immune system. Our 5-year experience with low-dose cyclophosphamide (CY) (350 mg/m2) before low-dose interleukin-2 (IL-2) (21.6 million IU/m2/d x 5 d/wk x 2 wk per course by IV bolus) is reviewed as an example of combination chemotherapy and immunotherapy. Twenty-six percent (10 of 39 evaluable patients) of patients with melanoma had major clinical responses; one other patient (2%) has had more than 48 months of response after a 40% regression of all tumors. Median survival was 18 months for responders and 8 months for the group as a whole. Eleven of 41 patients (27%) lived at least 12 months and four (10%) lived at least 2 years. Liver metastases regressed in 4 of 10 cases, with responses in lung, adrenal, skin, and lymph nodes but no bone. Toxicity was tolerable. A correlation between cytolysis of lymphocytes against a natural killer-resistant melanoma cell line (LAK-like activity) was found, but the role of LAK cells in vivo remains uncertain. No effect was noted in 15 patients with renal cancer, but regressions of breast cancer were found in a shortened trial with 13 patients. While the necessity for CY has not been established in these studies, the regimen of CY + IL-2 as it stands appears to have some clinical efficacy in at least two cancers.