Oxaliplatin-induced chronic peripheral neurotoxicity: a prospective analysis in patients with colorectal cancer

Kyung Kee Baek, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Yong Beom Cho, Seong Hyeon Yun, Hee Cheol Kim, Woo Yong Lee, Ho-Kyung Chun, Kyung Kee Baek, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Yong Beom Cho, Seong Hyeon Yun, Hee Cheol Kim, Woo Yong Lee, Ho-Kyung Chun

Abstract

Purpose: Oxaliplatin-induced chronic peripheral neurotoxicity (OXCPN) manifests as a loss of sensation and dysesthesia in the distal extremities, which may impair daily activities and increase in incidence with the amount of oxaliplatin delivered. The variation in the reported incidence and severity of OXCPN may be a consequence of differences in the baseline characteristics of patients.

Materials and methods: This was a prospective study (ClinicalTrials.gov, NCT00977717) in which OXCPN was recorded for all consecutive colon cancer patients treated at Samsung Medical Center (Seoul, Korea) with oxaliplatin-based combination chemotherapy. The primary endpoint was the incidence of severe OXCPN (grade 2 lasting for >7 days, or grade 3). The association of severe OXCPN and pretreatment parameters was evaluated using a multivariate regression model.

Results: Between Jan 2008 and Feb 2010, 100 patients treated with adjuvant folinic acid/fluorouracil plus oxaliplatin (FOLFOX) and 266 patients treated with capecitabine plus oxaliplatin (XELOX) or FOLFOX for advanced disease were registered into our study. The median cumulative dose of oxaliplatin was 796 mg/m(2) (range, 85 to 1,583 mg/m(2)). Severe OXCPN was observed in 126 (34%) patients. Overall, 43 patients discontinued chemotherapy due to toxicity: 23 without severe OXCPN and 20 with severe OXCPN. In univariate analysis, severe OXCPN was frequently observed in patients with age ≥55 years (p<0.01), stage II or III (p<0.01), adjuvant setting (p=0.01), FOLFOX (p<0.01), performance status of 0 (p=0.02), and those with no prior chemotherapy (p<0.01). In a multivariate regression model, the number of chemotherapy cycles and the cumulative oxaliplatin dose were not associated with the development of severe OXCPN.

Conclusion: We failed to find a significant association between patient characteristics at baseline and the development of severe OXCPN after oxaliplatin-based combination chemotherapy. Pharmacogenomic profiling using genome-wide association study in these patients is underway.

Keywords: Colorectal neoplasms; Neurotoxicity; Oxaliplatin.

Figures

Fig. 1
Fig. 1
Cumulative hazard of developing severe oxaliplatin-induced chronic peripheral neurotoxicity according to chemotherapy regimens. *folinic acid, 5-fluorouracil and oxaliplatin, †capecitabine and oxaliplatin.

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