Sequential cis-platinum and fludarabine with or without arabinosyl cytosine in patients failing prior fludarabine therapy for chronic lymphocytic leukemia: A phase II study

Patients with chronic lymphocytic leukemia (CLL) who fail fludarabine (Flud a) therapy have a poor response to subsequent salvage regimens and a poor p rognosis. This study was undertaken to determine the efficacy and toxicity of a cis-platinum, (cis-p)fluda and arabinosyl cytosine (ara-C) combination in patients who were refractory to fluda or had relapsed following prior f luda therapy for CLL. Forty-one patients who had progressive CLL were treat ed on study. Eleven patients (27%) were sensitive to fluda and thirty (73%) refractory prior to study entry. Therapy consisted of cis-p 100 mg/m(2) co ntinuous intravenous (IV) infusion over 4 days, fluda 30 mg/m(2) IV over 15 minutes on Days 3 and 4 either given alone (PF) or with ara-C 500 mg/m(2) IV over 1 hour on Day 4 (PFA). The median number of PF or PFA courses recei ved was two. No patient achieved a complete response. Eight patients (19%) achieved a partial response (PR), 28 were taken off study with progressive or refractory disease and 5 had induction deaths. The overall median surviv al was 6 months, 15 months in responding patients, and 4 months in non-resp onding patients. Rai stage I-II patients had a median survival of 7 months and stage III-IV patients had a median survival of 3 months. Major toxiciti es (myelosuppression, sepsis, renal failure and tumor lysis syndrome) were frequent. In conclusion, it can be said that the PF and PFA regimens have equivalent modest activity in patients with progressive CLL following prior fluda ther apy, predominantly among patients whose disease was sensitive to fluda at l ast prior exposure. Ara-C did not add to the activity of the cis-p/fluda co mbination in this study group.