A single center review of the experience with mitomycin C (MMC) and the risk of thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS)

Abstract

15167 Background: MMC related TTP/HUS has been reported between 4 and 15%, with a higher incidence in patients receiving cumulative doses of 60 mg or higher. It tends to occur within 4 months of drug administration independently of patients’ cancer status. The ability of MMC to upregulate enzymes relevant for new cytototoxic agents (topoisomerase I for CPT-11 and thymidine phosphorylase for capecitabine) make phamacobiologically based therapeutic combinations including MMC attractive. Methods: All patients (n=100) that participated in four institutional clinical studies from 2000 through 2004 were included. The studies were OSU 9947 (phase I trial of CPT-11 and MMC in solid tumors, n=31) OSU 0151 (phase II trial of CPT-11 and MMC in advanced esophageal and stomach cancer, n=41) OSU 0155 (phase II trial of CPT-11 and MMC in patients with refractory breast cancer, n=26) OSU 0330 (phase I study of capecitabine and MMC in patients with advanced GI tumors n=2). In each study, the maximum cumulative dose of MMC was 36 mg/m2. All patients were followed for clinical signs or symptoms of TTP/HUS including the presence of anemia, thrombocytopenia and renal insufficiency and had a thorough review of the peripheral smear. Results: The median cumulative dose was 12 mg/m2 (range 3–36 mg/m2). No patients met the clinical diagnosis of TTP/HUS except for one patient had anemia, thrombocytopenia and renal insufficiency but did not manifest any other findings consistent with TTP/HUS such as changes in mental status, azotemia or any other clinical symptom. The laboratory abnormalities resolved without intervention within seven days with subsequent continuation on the clinical trial. Conclusions: In this study we have demonstrated that by capping the cumulative dose of MMC to 36 mg/m2, the incidence of TTP/HUS is minimal. Furthermore, our preliminary analysis of an additional 100 patients treated with MMC at OSU shows no reported cases of TTP/HUS (additional data will be presented at the meeting). Since MMC is effective in a wide variety of solid tumors including breast, lung and GI malignancies and is inexpensive and easy to administer, further exploration of MMC in the treatment of solid malignancies is indicated including rational combination studies. No significant financial relationships to disclose.