A Prospective Analysis of Adverse Events in a Phase 2 Trial of Imatinib in the Treatment of Polycythemia Vera.

Imatinib has recently been demonstrated to be an effective treatment in Polycythemia Vera. Initial response rates are high, approaching 80%. Patients enrolled in our trial, Novartis CST 1571B (US 144), were asked to complete a questionnaire identifying side effects of imatinib known from previous trials in chronic myeloid leukemia and GIST. Questionnaires were completed weekly for the first month, biweekly for the second month, and monthly for the remainder of the study. Mean time on study is now 1.1 years. Target enrollment was 20 patients. Mean age was 54 years; male to female ratio was 1.3: 1. Fourteen patients were Caucasian and 2 African American. Twelve patients were naïve to treatment and 4 patients were previously treated with hydroxyurea. Two dose escalations were allowed sequentially to 600mg and 800mg daily based on response using the Polycythemia Vera Study Group Criteria. Toxicity was graded according to the NCI Common Toxicity Criteria, version 2.0. Patient reported toxicities are expressed as the total number of events reported during the 120 week study period. Diarrhea was the most common reported toxicity at 53 events. Periorbital edema (33), pruritis (39), fatigue (29), arthralgias (20), headache (18), nausea (19), reflux (38), and dry mouth (15) were the next most commonly reported events on study. Other toxicities reported less commonly were chest pain (3), depression (4), cough (5), insomnia (6), weight gain (3), taste changes (7), and depigmentation (3). Most toxicities were mild at grade 1 and resolved spontaneously within 30 to 40 weeks from the time of treatment initiation. The exceptions to this were diarrhea, periorbital edema, and reflux esophagitis, which persisted in a number of patients throughout the study. The severity of gastrointestinal side effects was dose dependent. Previous studies of imatinib induced toxicity in patients with chronic myeloid leukemia have reported cutaneous manifestations as the most common event. Our study demonstrates the toxicities of imatinib in patients with polycythemia vera are generally mild and self limited, although resolution may take up to 35 weeks. In contrast with studies of imatinib and chronic myeloid leukemia, gastrointestinal toxicity was more common and tended to persist, but did not result in patient withdrawal from study. These differences from our findings may be the result of several factors: the use of a patient reported adverse events scale, small trial size, or differences in drug metabolism in a related myeloproliferative disorder.