Randomized study of individualized induction therapy with or without vincristine, and of maintenance—intensification therapy between 4 or 12 courses in adult acute myeloid leukemia. AML-87 study of the Japan adult leukemia study group

Abstract

Background. It was assessed whether addition of vincristine (VCR) to remission induction therapy would increase the complete remission (CR) rate, and, secondarily, whether 12 courses of maintenance—intensification therapy would produce longer survival than 4 courses in adult acute myeloid leukemia (AML). Methods. A randomized comparison of individualized induction therapy was conducted between daunorubicin, behenoyl cytarabine, 6‐mercaptopurine, and prednisolone with or without VCR. After 3 courses of intensive consolidation therapy, maintenance—intensification therapy was randomized to 4 or 12 courses given every 6 weeks. Results. Of 265 patients registered, 252 were evaluable. CR was obtained in 78%; 80% in 205 patients of age younger than 60 years, and 65% in 47 of age 60 years or older. Addition of VCR reduced the CR rate significantly (84% to 70%, P = 0.007). Predicted 4‐year survival, continuing CR, and disease‐free survival (DFS) rates of 196 CR patients are 45%, 41%, and 35%, respectively. Patients receiving 12 courses of maintenance—intensification showed better DFS. By multivariate analyses, significant factors for achievement of CR were performance status 0 to 2, age younger than 60 years, and no VCR; and those for longer DFS were achievement of CR by one course, age younger than 50 years, and French—American—British (FAB) classification M3 or M5. Among 131 patients randomized to the maintenance, the administration of 12 courses was the most important factor (P = 0.0040) for longer DFS, followed by FAB M3 or M5, and by achievement of CR by one course. Conclusions. Addition of VCR in remission induction therapy was harmful, and longer intensive maintenance therapy prolonged DFS in adult AML.

Comparison between four and eight cycles of intensive chemotherapy in adult acute myeloid leukemia: a randomized trial of the Finnish Leukemia Group

“…4,7,12,14,19,29,30 The disease-free survival and overall survival are also comparable with other recent studies 1,5,19,31,32 and they are clearly longer than those of our previous multicenter trial with less intensive postremission therapy. 8 In this protocol an attempt was made to select refractory patients early and give them alternative chemotherapy.…”

“…1,10,20 On the other hand, a Japanese study reported a significantly longer disease-free survival when 12 moderately intensive cycles instead of four followed a consolidation phase. 14 The reasons for the different results are difficult to explain. Most results, including ours, suggest that the treatment given during the first few months after diagnosis of AML has the greatest impact on outcome.…”

“…32,34,35 Vincristine and corticosteroids have been previously utilized in several protocols due to their low myelotoxicity and a remission rate higher than 10% in AML. 37 However, Ohno et al 14 have recently shown that adding vincristine to daunorubicin, behenoyl cytarabine and mercaptopurine decreased the remission rate from 84 to 70%. So, vincristine does not seem to be indicated for the modern treatment of AML.…”

“…In at least two studies, however, maintenance treatment prolonged disease-free survival, 12,13 but benefit on overall survival was not seen in one of these studies. 13 In the study by Mandelli et al, 10 prolonged duration of moderately intensive consolidation treatment had no effect on disease-free survival or overall survival 10 but such treatment significantly increased disease-free survival in a report by Ohno et al 14 Several uncontrolled studies suggest that intensive postremission treatment is more effective than low-dose consolidation in prolonging remission. [15][16][17] Some controlled studies…”

“…19,20 Several intensive cycles have been given in some protocols, 4,14 but many recent approaches are based only on one, two or three courses of high-dose therapy as the sole postremission treatment. [15][16][17][18][19][21][22][23][24] Due to high morbidity, risk of mortality, and the high cost of each course of chemotherapy, it would be extremely important to know the duration of treatment necessary for a curative result, but currently the optimal number of intensive cycles is not known.…”