Prospective evaluation of the incidence of delayed nausea and vomiting in patients with colorectal cancer receiving oxaliplatin-based chemotherapy

Abstract

9645 Background: Oxaliplatin (OX) is a platinum compound commonly used in colorectal cancer. The emetogenic potential of OX has not been well characterized despite reports of frequent nausea (N) and vomiting/retching (V) in phase I and II studies. Platinum compounds such as cisplatin and carboplatin have a well defined ability to cause delayed (> 24 hours post chemotherapy) NV in the absence of antiemetic prophylaxis. There is no information available on the potential for OX to produce delayed NV.This trial sought to prospectively determine the frequency of delayed N and V with OX-based chemotherapy following day 1 prophylaxis with a 5-HT3 antagonist (5-HT3A) and dexamethasone (DEX). Methods: Eligibility: Pts ≥ age 18 with colon cancer receiving OX (85–100mg/m2) as part of a standard FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) regimen for the first time. Performance status: 0–2. Antiemetic treatment: 5-HT3A (ondansetron, dolasetron, or granisetron but not palonosetron) at an approved dose and DEX 20mg PO/IV on day 1 prior to OX infusion. No routine prophylaxis for delayed N/V was given. Episodes of V, N, and use of rescue antiemetics were recorded in patient-completed diaries. Four point (none, mild, moderate, severe) categorical scales were used to assess N. Study period: 120 hours after OX administration. Definitions: complete response (CR) - no V and no use of rescue antiemetics (RA); complete control (CC) - no V, no N and no RA. Results: Pts: 36; evaluable 35; median age: 68 (48–85); M/F 46%/54%. History of moderate - heavy ethanol use: 8 pts (23%). Acute CR: 91% (32/35); Delayed CR: 51% (18/35); Delayed CC: 40% (14/35); Overall CR (0–120 hrs): 51% (18/35); Overall CC: 37% (13/35). Median time to first emesis/first rescue: 57 hrs/47 hrs. Conclusions: The use of a single dose of a 5-HT3A and DEX prior to OX results in excellent control of emesis (CR - 91%) during the 24 hours after chemotherapy. However, without further antiemetic treatment, complete response rate in the delayed period (hours 24 - 120) decreased to 51%. In addition, a majority of pts (57%) noted delayed N, with N of moderate to severe intensity in 9 (26%) pts. This study supports the need for routine antiemetic prophylaxis for delayed N and V following OX-based chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis