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 ac ute myelogenous leukemia and the blastic phase of CML. Patients and me thods: Starting in April 1992, 17 consecutive patients with the blasti c 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 cy tarabine (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 t he time of their BP diagnoses, two patients showed extramedullary invo lvement, in eight patients the BP was preceded by an accelerated phase . Results: Overall, 11 of 17 patients (65%) achieved complete remissio n and 7 of 11 responding patients (64%) manifested a cytogenetic conve rsion ranging from 38% to 100% Ph-negative metaphases; one patient die d in CR of hemothorax, three died of sepsis during induction therapy a nd three patients (17.5%) had resistant disease. As of April 1996, fou r 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 t herapy. Profound myelosuppression was observed in all patients; extrah ematologic toxicity, especially involved the gastrointestinal tract, w ith grade >2 mucositis in five patients (29.5%) and liver dysfunction in five (29.5%). No renal toxicity or ototoxicity was observed. Conclu sions: Despite the brief relapse-free duration, the high remission rat e and tolerable toxicity indicate that the VAC combination chemotherap y has a high antileukemic efficacy, and warrants further evaluation fo r the treatment of CML in acute phase, provided a post-remission BMT s trategy is feasible.