Cyclophosphamide, Methotrexate and 5-Fluorouracil Combination Chemotherapy Versus Chloroethyl-Cyclohexy-Nitrosourea in the Treatment of Metastatic Prostatic Cancer

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Abstract
The effect of cyclophosphamide, methotrexate and 5-fluorouracil combination chemotherapy was compared to the single agent, chloroethylcyclohexy nitrosourea, in the treatment of hormonally refractive metastatic prostatic carcinoma. All patients could be evaluated and were followed for at least 2 yr or until death. Responses were defined by the National Prostatic Cancer Project criteria [USA]. Of 20 patients who received cyclophosphamide, methotrexate and 5-fluorouracil 3 (15%) had partial (median duration of 2.5 mo.), 4 (20%) had stable (median duration of 5 mo.) and 13 had progression of the disease. Of 20 patients who received chloroethylcyclohexy nitrosourea none had a partial response, 6 (30%) had stability (median duration of 6.2 mo.) and 13 had progression of the disease. The overall response rate for patients receiving cyclophosphamide, methotrexate and 5-fluorouracil was 35% (stable plus partial regressions) and it was 30% for those receiving chloroethylcyclohexynitrosourea (stable only). Subjective improvement was noted in all 7 patients who responded to combination chemotherapy and in 3 of the 6 patients who responsed to the single agent. After 2 courses resistant patients were crossed over to the opposite regimen and none had an objective, stable or subjective response. Although the duration of response was short (2-6 mo.) patients with partial regressions or stabilized disease survived longer (P < 0.05) than patients whose disease progressed (52 vs. 24 wk, respectively). The mean interval from diagnosis to chemotherapy (lead time) was 40 mo. for patients who responded to chemotherapy compared to 19 mo. for those with progression, which suggested a slower growing pattern of disease in those who did respond. There was no improvement in cohort survival with either treatment regimen. Over-all response rates to cyclophosphamide, methotrexate and 5-fluorouracil were not superior to reported responses to cyclophosphamide alone, and both treatment regimens appeared to be only marginally effective in the treatment of endocrine-resistant, advanced prostatic cancer.