Kruger Stephan, Boeck Stefan, Heinemann Volker, Laubender Ruediger P, Vehling-Kaiser Ursula, Waldschmidt Dirk, Kettner Erika, Märten Angela, Winkelmann Cornelia, Klein Stefan, Kojouharoff Georgi, Gauler Thomas C, Fischer von Weikersthal Ludwig, Clemens Michael R, Geissler Michael, Greten Tim F, Hegewisch-Becker Susanna, Modest Dominik P, Stintzing Sebastian, Haas Michael
Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich , Munich , Germany.
Acta Oncol. 2015 Jul;54(7):993-1000. doi: 10.3109/0284186X.2015.1034877. Epub 2015 Apr 30.
Drug-induced skin toxicity may correlate with treatment efficacy in cancer patients receiving chemotherapy or biological agents. The correlation of the capecitabine-associated hand-foot skin reaction (HFS) on outcome parameters in pancreatic cancer (PC) has not yet been investigated.
Within the multicentre phase III AIO-PK0104 trial, patients with confirmed advanced PC were randomly assigned to first-line treatment with either capecitabine plus erlotinib (150 mg/day, arm A) or gemcitabine plus erlotinib (150 mg/day, arm B). A cross-over to either gemcitabine (arm A) or capecitabine (arm B) was performed after failure of the first-line regimen. Data on skin toxicity were correlated with efficacy study endpoints using uni- and multivariate analyses. To control for guarantee-time bias (GTB), we focused on subgroup analyses of patients who had completed two and three or more treatment cycles.
Of 281 randomised patients, skin toxicity data were available for 255 patients. Median time to capecitabine-attributed HFS was two cycles, 36 of 47 (77%) HFS events had been observed by the end of treatment cycle three. Considering HFS during first-line treatment in 101 patients treated with capecitabine for at least two cycles within the capecitabine plus erlotinib arm, time to treatment failure after first- and second-line therapy (TTF2) and overall survival (OS) both were significantly prolonged for the 44 patients (44%) with HFS compared to 57 patients without HFS (56%) (TTF2: 7.8 vs. 3.8 months, HR 0.50, p = 0.001; OS: 10.4 vs. 5.9 months, HR 0.55, p = 0.005). A subgroup analysis of 70 patients on treatment with capecitabine for at least three cycles showed similar results (TTF2: 8.3 vs. 4.4 months, HR 0.53, p = 0.010; OS: 10.4 vs. 6.7 months, HR 0.62, p = 0.056).
The present subgroup analysis from AIO-PK0104 suggests that HFS may serve as an independent clinical predictor for treatment outcome in capecitabine-treated patients with advanced PC.
在接受化疗或生物制剂治疗的癌症患者中，药物引起的皮肤毒性可能与治疗效果相关。卡培他滨相关的手足皮肤反应（HFS）与胰腺癌（PC）预后参数之间的相关性尚未得到研究。
在多中心III期AIO-PK0104试验中，确诊为晚期PC的患者被随机分配接受一线治疗，方案为卡培他滨联合厄洛替尼（150毫克/天，A组）或吉西他滨联合厄洛替尼（150毫克/天，B组）。一线治疗方案失败后，交叉使用吉西他滨（A组）或卡培他滨（B组）。使用单因素和多因素分析将皮肤毒性数据与疗效研究终点相关联。为控制保证时间偏差（GTB），我们重点对完成两个及三个或更多治疗周期的患者进行亚组分析。
在281例随机分组的患者中，255例患者有皮肤毒性数据。卡培他滨引起的HFS的中位时间为两个周期，在治疗周期三结束时观察到47例HFS事件中的36例（77%）。在卡培他滨联合厄洛替尼组中，对101例接受卡培他滨治疗至少两个周期的患者进行一线治疗期间的HFS分析，与57例无HFS的患者（56%）相比，44例有HFS的患者（44%）一线和二线治疗后的治疗失败时间（TTF2）和总生存期（OS）均显著延长（TTF2：7.8个月对3.8个月，HR 0.50，p = 0.001；OS：10.4个月对5.9个月，HR 0.55，p = 0.005）。对70例接受卡培他滨治疗至少三个周期的患者进行亚组分析，结果相似（TTF2：8.3个月对4.4个月，HR 0.53，p = 0.010；OS：10.4个月对6.7个月，HR 0.62，p = 0.056）。
来自AIO-PK0104的本次亚组分析表明，HFS可能是卡培他滨治疗的晚期PC患者治疗结局的独立临床预测指标。
