Amifostine pretreatment for patients with advanced colorectal cancer receiving folfox chemotherapy

Abstract

19663 Background: Oxaliplatin plays a key role in the treatment of advanced colorectal cancer (CRC) but is associated with dose- limiting peripheral neuropathy (PN) in >20% of patients. We investigated the effects of amifostine, a cytoprotective agent, on the prevention of PN in patients receiving oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFOX) for the treatment of advanced (stage =III) CRC. Methods: In this ongoing prospective observational study, patients with stage =III CRC are assigned to receive FOLFOX alone (oxaliplatin 85 mg/m2, 5-FU 400 mg/m2 bolus, 5-FU 1.2 or 2.4 g/m2 continuous infusion over 46 h, LV 200 or 400 mg/m2) or FOLFOX plus 500 mg subcutaneous amifostine 30 minutes before chemotherapy. Some patients also receive bevacizumab and/or panitumumab. All patients receive Ca/Mg infusion (1 g each/100 mL normal saline) before and after oxaliplatin treatment. Incidence and degree of PN are assessed during biweekly patient interviews and graded using National Cancer Institute Common Toxicity Criteria Version 3. Results: Sixteen patients have enrolled to date (9 nonamifostine, 7 amifostine; mean age, 60.2 y [range, 33–81 y]; 81% men). Currently, data for 6 patients (3 per group) who have completed 12 cycles of therapy are available. Two of 3 patients in the nonamifostine group reported PN grade =2 during treatment; 1 of these patients required multiple treatment interruptions because of grade 3 PN. The third nonamifostine patient reported grade 1 PN on only 2 occasions during treatment but experienced grade 2 PN at 3-month follow-up. No patient in the amifostine group reported grade =2 PN during the treatment period. One amifostine patient required a reduction in oxaliplatin dose after 8 cycles because of neutropenia. At 3-month follow-up, 1 amifostine-treated patient reported grade 1 tingling in his hands and is currently receiving treatment with pregabalin. Conclusions: The use of amifostine for the prevention of oxaliplatin-induced PN is investigational. Patients with advanced CRC who received amifostine with FOLFOX chemotherapy had a decreased incidence and severity of PN compared with patients who did not receive amifostine. Updated data will be available at the time of presentation; study enrollment continues. No significant financial relationships to disclose.