We investigated whether rechallenge with oxaliplatin (OXA) can worsen the pre‐existing oxaliplatin‐induced peripheral neurotoxicity (OXAIPN) in metastatic colorectal cancer (mCRC) patients. Patients previously treated with OXA, having clinically significant grade 1 or 2 OXAIPN were assessed, after receiving rechallenge with OXA, using the clinical version of the Total Neuropathy Score (TNSc). Peripheral neuropathy was assessed at the end of first OXA exposure and at completion of OXA rechallenge. The first line OXA‐based chemotherapy was completed at least 9 months earlier (OXA‐free interval). We studied 25 mCRC patients, 14 males and 11 females, with a median age of 63 (35‐77) years. After their first exposure to OXA‐based chemotherapy, 9 (36%) patients developed grade 1 OXAIPN and 16 patients grade 2 (64%) neurotoxicity. OXA reintroduction with a median of 10 (8‐14) cycles led to grade 1 OXAIPN in two patients (8%), grade 2 in 19 patients (76%), and grade 3 neuropathy in 4 (16%) patients Worsening of pre‐existing OXAIPN was documented in seven (28%) patients and was significantly associated with higher OXA delivered cumulative dose (P < .001). Median TNSc scores following treatment (10; range 4‐18) were significantly increased (P < .001), when compared to the scores recorded at the end of first line treatment (8; range 2‐12). Rechallenging OXA appears to relatively worsen the severity of existing OXAIPN. However, the majority of rechallenged patients developed a clinically significant (grade 2) OXAIPN, rather than treatment‐emergent grade 3. As such, OXA rechallenge might be a feasible option in patients previously having OXAIPN.

中文翻译：

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奥沙利铂在具有临床显着奥沙利铂诱导的周围神经毒性的转移性结直肠癌患者中的再激发

我们研究了奥沙利铂 (OXA) 再激发是否会加重转移性结直肠癌 (mCRC) 患者中原有的奥沙利铂诱导的外周神经毒性 (OXAIPN)。先前接受过 OXA 治疗、具有临床意义的 1 级或 2 级 OXAIPN 的患者在接受 OXA 再激发后，使用总神经病变评分 (TNSc) 的临床版本进行评估。在第一次 OXA 暴露结束时和 OXA 再激发完成时评估周围神经病变。基于 OXA 的一线化疗至少提前 9 个月完成（无 OXA 间隔）。我们研究了 25 名 mCRC 患者，14 名男性和 11 名女性，中位年龄为 63 (35-77) 岁。在首次接受基于 OXA 的化疗后，9 名 (36%) 患者出现 1 级 OXAIPN，16 名患者出现 2 级 (64%) 神经毒性。P  < .001）。 与一线治疗结束时记录的评分（8；范围 2-12）相比，治疗后的中位数 TNSc 评分（10；范围 4-18）显着增加（P < .001）。再次挑战 OXA 似乎会相对加重现有 OXAIPN 的严重程度。然而，大多数再次激发的患者出现了具有临床意义的（2 级）OXAIPN，而不是治疗出现的 3 级。因此，对于先前患有 OXAIPN 的患者，再次激发 OXA 可能是一个可行的选择。