Evaluation of alternating chemotherapy and sites and extent of disease in extensive small cell lung cancer.

Sixty-six patients were entered into a prospective, randomized clinical trial evaluating the use of alternating noncross-resistant chemotherapy in patients with extensive small cell carcinoma of the lung. Sixty-five were evaluable. One regimen utilized cyclophosphamide, VP-16, vincristine, cisplatin alternating with doxorubicin (Adriamycin) and DTIC (CVVP-AD). The second regimen utilized doxorubicin, VP-16, vincristine, and cisplatin alternating with cyclophosphamide and DTIC (AVVP-CD). There was no statistically significant difference between the two chemotherapeutic programs in terms of regression rate, time to progression, or survival. Overall regression rate for CVVP/AD was 91% (29/32) including five complete regressions (CRs). For AVVP-CD, the total regression rate was 82% (27/33) including nine CRs. Combined, the overall regression rate was 86% with a CR rate of 22%. Time to progression for CVVP-AD and AVVP-CD was 28 and 26 weeks, respectively. The median survival time of CVVP-AD and AVVP-CD regimens was 40 and 42 weeks, respectively. Prognostic variables significantly correlated with survival were performance score and extensive liver metastases at diagnosis. Correlations between initial sites of disease led to the observation that patients with no central nervous system (CNS) metastases at diagnosis were more likely to have more extensive liver and lung involvement. Further analysis revealed the lung to be the most common site of first progression (46%) and liver second (28%). Patients with extensive involvement of the liver or lung progressed sooner in these sites than those with a lesser tumor extent. At some point in the study, 40% of the patients experienced CNS metastases. The efficacy of these two alternating regimens is comparable to most current regimens reported in extensive SMCLC. Whether cyclophosphamide or doxorubicin is used first seemed to make little difference. The alternate noncross-resistant regimen was rarely effective in producing tumor regression following initial progression.