Alternating non-cross-resistant drug combinations in the treatment of metastatic small-cell carcinoma of the lung.
In a randomized trial of the Southeastern Cancer Study Group, patients with metastatic small-cell lung carcinoma were treated with a combination of cyclophosphamide (500 mg/m2 I.V.), Adriamycin (50 mg/m2 I.V.), DTIC (250 mg/m2 I.V.), and vincristine (1 mg/m2 I.V.) every 4 weeks for three cycles. Complete and partial responders to this induction regimen were then randomized to receive either the same combination every 4 weeks for an additional six cycles versus a non-cross-resistant drug combination of BCNU (100 mg/m2 I.V.), procarbazine (100 mg/m2 p.o. daily x 10 days), methotrexate (25 mg/m2 I.V.), and vinblastine (5 mg/m2 I.V.) every 4 weeks for six cycles versus alternating treatments with the two regimens for a total of six cycles of therapy. Patients who were less than good responders received six cycles of the non-cross-resistant drug combination. Of 202 evaluable patients, 40% responded (complete + partial responses) to induction; the complete response rate for the whole group was low (14%). Patients randomized to the BPMV combination, or crossed over to it, failed to improve upon their response to induction. Patients who responded to induction had a median survival of 41 weeks versus 20.6 weeks for the nonresponders, p less than 0.001. Performance status greater than or equal to 60%, and absence of prior radiotherapy were associated with improved survival (30 and 31.5 weeks, respectively). The toxicity of these regimens was acceptable. Failure to improve on results of our earlier protocol were probably due to the long (weeks) interval between treatments, inclusion of a relatively inactive but toxic drug (DTIC) in the induction combination which limited doses of the more active agents, and the use of a non-cross-resistant drug regimen which was inactive.