Etoposide, intermediate-dose cytarabine and carboplatin (VAC): A combination therapy for the blastic phase of chronic myelogenous leukemia

Background: Carboplatin is a second-generation platinum compound that in combination with etoposide and intermediate doses of cytarabine, in early clinical trials has demonstrated high efficacy in refractory acute myelogenous leukemia and the blastic phase of CML. Patients and methods: Starting in April 1992, 17 consecutive patients with the blastic phase (BP) of chronic myelogenous leukemia (CML) and a median age of 33 years (range 10 to 45) received a new treatment regimen consisting of etoposide (100 mg/m(2)/d i.v. over one hour), intermediate-dose cytarabine (500 mg/m(2)/d i.v. over one hour, q12 hours) and carboplatin (150 mg/m(2)/d continuous infusion) on days 1-3 and 8-10 (VAC regimen). The BP phenotype was myeloid in 16 patients and hybrid in one. At the time of their BP diagnoses, two patients showed extramedullary involvement, in eight patients the BP was preceded by an accelerated phase. Results: Overall, 11 of 17 patients (65%) achieved complete remission and 7 of 11 responding patients (64%) manifested a cytogenetic conversion ranging from 38% to 100% Ph-negative metaphases; one patient died in CR of hemothorax, three died of sepsis during induction therapy and three patients (17.5%) had resistant disease. As of April 1996, four patients are alive, three of them in first remission at +7, +10, +16 months after CR, and one in BP at +38 months after the start of VAC therapy. Profound myelosuppression was observed in all patients; extrahematologic toxicity, especially involved the gastrointestinal tract, with grade >2 mucositis in five patients (29.5%) and liver dysfunction in five (29.5%). No renal toxicity or ototoxicity was observed. Conclusions: Despite the brief relapse-free duration, the high remission rate and tolerable toxicity indicate that the VAC combination chemotherapy has a high antileukemic efficacy, and warrants further evaluation for the treatment of CML in acute phase, provided a post-remission BMT strategy is feasible.