Phase II study of caphosol oral rinse for prevention of oral mucositis (OM) in sarcoma patients (pts) receiving multicycle doxorubicin-based chemotherapy (CT): Randomized study with cross-over to palifermin for severe OM.

Abstract

e19520 Background: Mucositis is a common complication in cancer pts receiving CT. We have shown that palifermin (recombinant Keratinocyte Growth Factor), administered as single dose prior to CT, alleviated severe mucositis in pts receiving doxorubicin-based CT (Ann Int Med 2010). Caphosol is a supersaturated electrolyte solution of calcium phosphate that has been indicated as oral rinse for xerostomia and as an adjunct to treat OM induced by radiation or high-dose CT. Purpose of the study was to evaluate the preliminary efficacy of Caphosol in pts receiving CT. Methods: Pts were randomized 1:1 to Caphosol vs. baking soda (control) as an oral rinse five times daily from initiation of CT. All pts received doxorubicin (75 or 90 mg/m2 by continuous infusion over 3 days) with ifosfamide (10 gm/m2) or cisplatin (120 mg/m2). Pts that experienced Grade (Gr) > 3 mucositis received palifermin (180 mcg/kg) iv 3 days before CT in subsequent cycles. Results: 28 of 30 pts received treatment and were evaluble; 15 men and 13 women, with median age 51 (range, 20-65 yrs). Incidence of Gr > 2 OM was 57% (8 of 14 pts) for Caphosol vs. 86% (12 of 14) for control (P=0.21). Incidence of Gr > 3 OM was 29% (4/14) for Caphosol vs. 43% (6/14) for control (P=0.43). However, the benefit was limited to oral but not other GI mucosal sites. Of 10 pts (Caphosol: 4, BS: 6,) with Gr > 3 OM, 6 crossed over to palifermin (Caphosol: 3, BS: 3); the other 4 pts (Caphosol: 1, BS: 3) came off the study. All 6 pts, that received palifermin, avoided severe OM in the next cycle. The median duration of Gr > 2 OM in the cycle before cross-over was 8 days (range: 5-12) vs. 0 days (0-3) in palifermin cycle (p=0.0032) and Gr > 3 OM was 5 days (2-7) vs. 0 days (p=0.0015). Oral assessment and the pts-reported outcome were in substantial agreement for the OM grading (weighted kappa, 0.78, 95% CI: 0.44-0.87, p<0.0001). No serious adverse event related to the study drug was observed. Conclusions: There was a trend for less severe OM with Caphosol vs. control. Secondary prophylaxis with palifermin alleviated severe mucositis in all pts who previously experienced severe mucositis during multi-cycle CT.