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 (Fluda) therapy have a poor response to subsequent salvage regimens and a poor prognosis. 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 fluda therapy for CLL. Forty-one patients who had progressive CLL were treated on study. Eleven patients (27%) were sensitive to fluda and thirty (73%) refractory prior to study entry. Therapy consisted of cis-p 100mg/m² continuous intravenous (IV) infusion over 4 days, fluda 30 m/m² IV over 15 minutes on Days 3 and 4 either given alone (PF) or with ara-C 500 mg/m IV over 1 hour on Day 4 (PFA). The median number of PF or PFA courses received 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 survival was 6 months, 15 months in responding patients, and 4 months in non-responding patients. Rai stage 1-11 patients had a median survival of 7 months and stage 111-IV patients had a median survival of 3 months. Major toxici-ties (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 therapy, predominantly among patients whose disease was sensitive to fluda at last prior exposure. Ara-C did not add to the activity of the cis-plfluda combination in this study group.