Palonosetron (PALO) + dexamethasone (DEX) for prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) in patients receiving multiple-day cisplatin CT for germ cell cancer

Abstract

8607 Background: Fractionated cisplatin is highly emetogenic; despite 5HT3 receptor antagonists + DEX, patients still experience acute and delayed CINV. PALO, a novel 5HT3 antagonist, is superior to conventional 5HT3 antagonists in protecting patients from emesis with a 0.25-mg IV dose prior to single-day CT. To assess the efficacy and safety of PALO in 40 patients with germ cell tumors receiving multiple-day cisplatin-based CT, a phase II multicenter study is being conducted. Methods: Adult men receiving 5-day cisplatin-based (20 mg/m2/d) CT received PALO 0.25 mg IV 30 min before CT on days 1, 3, and 5 and DEX 20 mg qd (po or IV 30 min before CT) on days 1–2; 8 mg po bid on days 6–7; and 4 mg po bid on day 8. Rescue medication was allowed at investigator discretion. Endpoints included emetic episodes (EE), nausea intensity, and rescue use, recorded in diaries for 9 consecutive 24-h periods. Interference with functioning due to nausea on a 4-point scale (none, a little bit, quite a bit, very much) was assessed with the validated Osoba nausea module on days 1, 5, and 10; safety was assessed at all follow-up encounters. Results: To date, 32 patients are evaluated, median age 35 years, 81% CT-naïve. Prior to CT, 97% of patients reported no more than a little interference with functioning from nausea. Most patients reported no significant interference with functioning due to nausea on days 1–4 of cisplatin (73% reported none/a little bit) and days 5–9 (87% none/a little bit). PALO + DEX was well tolerated; treatment-related adverse events were mild-moderate headache (18.8%), constipation (6.3%), and abdominal pain (3.1%), none serious. Conclusions: Three doses of PALO + 5 doses of DEX over an 8-day period effectively prevented both emesis and significant nausea in the majority of patients with germ cell tumors receiving multiple-day cisplatin-based CT. This regimen appears to be an improvement over historical CINV control. [Table: see text] [Table: see text]