Alternating combination chemotherapy does not delay development of refractoriness in myeloma

Sixty-seven patients with stage II and III myeloma were subjected to 3 consecutive prospective phase II studies. Nineteen patients had received melphalan - prednisolone (melphalan group), 17 cyclophosphamide - vincristine - prednisolone (cyclophosphamide group) and 22 alternating combinations of 7 cytostatics and prednisolone (alternating group). Nine patients were unevaluable. The median time until response was achieved was 5, 5 and 3 months respectively. The purpose of the study was to see if combination or alternating combination chemotherapy can delay the appearance of refractoriness. Patients were regarded as refractory after progression, which was defined as advance from stage II to stage III, and, in stage III as an increase of the monoclonal serum protein of more than 25% and/or the monoclonal urine protein of more than 100% despite continued treatment. Refractoriness was not delayed by alternating combination treatment. Thirty per cent of the patients became refractory after 10 months of response in the melphalan group and after 11 months in the cyclophosphamide and the alternating chemotherapy groups. The results remained after stratification for stage.