TREATMENT OF REFRACTORY MULTIPLE-MYELOMA WITH VINCRISTINE, ADRIAMYCIN, DEXAMETHASONE, AND WITH REPEATED APPLICATION OF CYCLOPHOSPHAMIDE (C-VAD)

The quick reduction of differentiated myeloma cells by VAD chemotherap y (vincristine, adriamycin, dexamethasone) causes, according to the in vestigation by Bell et al., the acceleration of the proliferation of m yeloma stem cells. In 1990 Bell demonstrated that this proliferation c ould be stopped by administering 500 mg of cyclophosphamide in 1-week intervals. We therefore modified the classical VAD scheme to the follo wing ''C-VAD'' scheme: vincristine 0.5 mg/day in countinuous infusion on the first to the 4th day, adriamycin 9 mg/m(2)/day in continual inf usion on the Ist to the 4th day, dexamethasone 40 mg p.o. or i.v. alwa ys on 4 days starting with the 1st, 10th and 20th days, cyclophosphami de 600 mg i.v. on the 5th, 10th and 20th days). A further cycle follow s on the 28th day. In the present paper the effect and the tolerance o f this C-VAD scheme is evaluated: In the group of 21 patients with ref ractory myeloma 9 remissions were achieved, 5 partial remissions, in 6 patients the disease progressed, 1 patient died after the 2nd cycle w ithout the possibility of evaluating the therapeutic response. The mea n remission length was 10.2 months. The tolerance of chemotherapy was satisfactory, C-VAD chemotherapy did not cause any serious drop in the number of leucocytes and thrombocytes. Echocardiographically lower ad riamycin cardiotoxicity was demonstrated in continual administration i n comparison with the bolus administration. The C-VAD scheme is consid ered to be suitable for comparison with the VAD chemotherapy in a rand omized study.