Relationship between myelosuppression and chemotherapeutic response in small cell bronchogenic carcinoma

Most cancerocidal agents have myelosuppression as their major toxicity. In some clinical studies it has been possible to show a relationship between the amount of administered drug and the therapeutic efficacy. Within any defined protocol, however, there may be much variability in the severity of myelosuppression. We attempted to determine whether the tumor response might be related to this toxicity. We evaluated a total of 177 patients with small cell bronchogenic carcinoma, treated by five successive regimens of combination chemotherapy, consisting of either cyclophosphamide and vincristine alone or with doxorubicin or doxorubicin plus bacillus Calmette-Guerin (BCG) or doxorubicin plus methotrexate, for a number of prognostic factors (age, sex, extent of disease, performance status, sites and number of metastases, serum LDH and alkaline phosphatase, weight loss, leukopenia, and thrombopenia). Leukopenia (mean 415 +/- 478/mm3, range 0-2000/mm3) had a weak influence on the incidence of complete remission, which was highest with the least severe nadir (P = 0.027). Thrombopenia was a nonsignificant factor (P = 0.738). Both leukopenia and thrombocytopenia had no influence on the overall survival. Because these drug combinations were based on cyclophosphamide, which requires metabolic activation, we evaluated the relationship of myelosuppression and the incidence of response in a second group of patients with small cell bronchogenic carcinoma treated with a VP16, cyclophosphamide, doxorubicin, vincristine sulfate protocol. In this analysis, no relationship could be detected between remission and myelosuppression. Granulocytopenia or thrombocytopenia also-showed no significant influence on the achievement of long-term survival beyond 36 months.