Addition of gabapentin (G) to a modified FOLFOX regimen does not reduce neurotoxicity in patients (pts) with advanced colorectal cancer (CRC)

Abstract

3581 Background: In order to determine the neuroprotectant effect of G against oxaliplatin-induced neurotoxicity, we sequentially recruited pt cohorts in a non-randomised phase II trial to FOLFOX then FOLFOX+G. Inclusion criteria were: advanced CRC; chemonaive except adjuvant completed ≥ 6 mths; measurable disease; PS 0–2. Pts received on D1 oxaliplatin 100mg/m2 IV over 2 hrs, LV 20mg/m2 bolus, 5-FU 400mg/m2 bolus then 5FU 2.4g/m2 46-hour infusion. Cycles were 2-wkly until PD or unacceptable toxicity. In addition, G cohort pts received G 300mg/d po, increased as required by 300mg/d increments (max 1800mg). Over 2 yrs, 40 pts were recruited to FOLFOX then 41 to FOLFOX+G. Minimum f/up was 18 mths. All but one pt received at least one dose of oxaliplatin and were evaluable for toxicity and treatment delivery. Pt characteristics were well balanced between cohorts. Maximum doses of G were 300mg/d in 10 pts, 600mg/d in 15, 900mg/d in 4, 1200mg/d in 9, and 1800mg/d in 3 pts. Treatment delivery for FOLFOX and FOLFOX+G cohorts respectively: median cycles 10 (1–13) vs 9 (1–12); oxaliplatin dose reduction >10% in 55% vs 50% of pts; cycles delayed >2days 19% vs 14%; treatment cessation due to toxicity 36% vs 37% (NS). RDI for FOLFOX and FOLFOX+G was oxaliplatin 82% vs 87%; 5FU bolus 52% vs 69%; 5FU infusion 82% vs 87% (NS). Responses (CR+PR) were seen in 48% of pts in each cohort. There were no significant difference in non-neurological toxicity.There was no significant difference in severity of neurotoxicity. For pts with grade 2/3 neurotoxicity, median time to recovery to grade 0/1 was 3.3mths for FOLFOX and 0.5mths for FOLFOX+G, however persistence of grade 2/3 neurotoxicity at 1 yr was 0% vs 17% respectively (NS). Conclusions: Addition of G to FOLFOX does not improve ability to deliver protocol-specified treatment and does not significantly reduce either severity or duration of neurotoxicity. This trial was sponsored by Sanofi-Synthelabo. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi Sanofi Sanofi Sanofi