PHASE-III STUDY COMPARING VINCRISTINE, DOXORUBICIN (ADRIAMYCIN), AND DEXAMETHASONE (VAD) CHEMOTHERAPY WITH VAD PLUS RECOMBINANT INTERFERON ALFA-2 IN REFRACTORY OR RELAPSED MULTIPLE-MYELOMA - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP STUDY

Purpose. This clinical trial was designed to compare the effectiveness of vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) wit h VAD plus interferon alfa-2 in patients with refractory or relapsed m ultiple myeloma. Patients and Methods. Between January 1990 and May 19 92, 47 eligible patients with multiple myeloma who had failed one prio r chemotherapeutic regimen were accrued to a multiinstitutional prospe ctive randomized clinical trial. The trial was halted early because of poor accrual. Results. After a minimum follow-up of 13 months, the ob jective overall response rate was 28% (25% in the VAD group, 30% in th e VAD plus interferon group). The response duration and overall surviv al were similar for the two treatment groups, with medians of 3.6 and 8.3 months, respectively. Life threatening or lethal nonhematologic to xicity was seen in 27%. Interferon did not appear to increase the freq uency of toxic responses. Conclusion. This study shows no advantage to the use of interferon combined with VAD in refractory or relapsing my eloma. However, the small sample size decreased the statistical power to recognize small differences if present. Moreover, the survival data do not suggest a clear advantage to the administration of vincristine or doxorubicin as a 96-hour infusion compared with results of studies using bolus administration combined with high-dose corticosteroids.