Heated oxaliplatin infusion (37°C) in combination with capecitabine for metastatic colorectal cancer: Can it reduce oxaliplatin-associated neuropathy?

Abstract

20660 Background: Combination chemotherapy with capecitabine (Cap) and oxaliplatin (Ox) is a standard regimen in metastatic colorectal cancer (MCRC). Ox-associated neuropathy (NP) remains a dose-limiting toxicity. No preventive strategy has been established. Because Ox NP is triggered by cold we hypothesized that infusing Ox at 37°C (H-Ox) might reduce NP. Methods: 20 patients (pts) were included in an open label trial. Eligible pts had MCRC, NP ≤ grade 1, adequate organ function and had received no prior Ox- chemotherapy. Treatment consisted of Cap 1,000mg/m2 bid on days 1–14 and Ox 130mg/m2 on day 1 of a 3 weeks cycle for a maximum of 6 cycles. The Ox infusion was administered through a fluid-warming device (FLUIDO, The Surgical Company BV) in 1L dextrose 5% at a constant temperature of 37°C over 2 hours. The primary endpoint was feasibility and drug reactions during the infusion. Secondary endpoints included acute and chronic NP, assessed by patient-based National Cancer Institute questionnaire (Leonard GD, BMC Cancer 2005) and NCI CTC version 3, and tumor response rate (RECIST). Results: Between July 06 and June 07 20 pts were enrolled. Median age was 71 years. Eligible pts had PS 0–1; 65% ≥ 2 sites of metastases. 11 pts completed six cycles, main reason for early discontinuation was progressive disease (4 pts). A total of 95 cycles were administered. Median cumulative Ox dose was 735 mg/m2. One patient experienced a laryngeal spasm shortly after the end of H-Ox infusion. No other infusion-related adverse event was observed. 35% of patients reported grade 3/4 acute dysesthesia or paresthesia. Chronic NP was observed in 85% (grade 1) and 15% (grade 2) respectively. Other treatment related grade 3/4 toxicities included diarrhea (15%), nausea (15%), thrombocytopenia (10%), pulmonary embolism (10%) and fatigue (15%). Overall response rate was 45% (95% CI 23–67%; 5% CR; 40% PR) and stable disease was achieved in 30% for a disease control rate of 75% (95% CI 56–94%). Conclusions: Administration of H-Ox in combination with Cap is feasible and well tolerated without additional toxicity. H-Ox has a low rate of chronic cumulative NP, however acute NP might be increased by infusion of H-Ox. Further investigation is warranted to compare Ox versus H-Ox. No significant financial relationships to disclose.