A multi-center phase II study of oxaliplatin, irinotecan, and capecitabine in advanced gastric/gastroesophageal junction carcinoma
A multi-center phase II study of oxaliplatin, irinotecan, and capecitabine in advanced gastric/gastroesophageal junction carcinoma
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DOI：
10.1007/s00280-008-0807-6
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发表时间：
2009-04-01
影响因子：
3
通讯作者：
Remick, Scot C.
中科院分区：
文献类型：
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作者：
Brell, Joanna M.;Krishnamurthi, Smitha S.;Remick, Scot C.
晚期胃和胃食管交界处（GEJ）腺癌没有标准的一线治疗，预后仍然很差。我们的机构进行了一项关于奥沙利铂、伊立替康和卡培他滨每周一次给药的I期研究。该方案是耐受的;药效学研究显示没有药物相互作用，并且在胃癌患者中有一个确认的反应。我们在晚期胃癌和GEJ腺癌中进行了一项II期试验，以确定缓解率和缓解持续时间。这是一项涉及6个地点的多中心单治疗组研究。仅允许既往接受辅助治疗。患者的ECOG体能状态为0-2，器官功能良好，能够耐受口服药物。所有患者均接受奥沙利铂60 mg/m2静脉注射（IV）和伊立替康50 mg/m2静脉注射，每周一次，共4周，停药2周。每周第1天至第5天口服卡培他滨450 mg bid，持续4周，然后休息2周。在前两个周期后评估患者的反应;还记录反应持续时间、总生存期和不良事件。我们估计历史缓解率提高30%将具有临床意义。共招募了39例患者，所有患者均进行了毒性评估; 30例患者可评价缓解。中位年龄为57.8岁（31-79岁），74%为男性。2例患者完全缓解，9例患者部分缓解。总缓解率为28%，其中9例患者无法评估缓解。中位缓解持续时间为5.97个月，中位总生存期为8.98个月。无5级治疗相关事件，所有死亡均继发于疾病进展。仅发生5例4级事件（中性粒细胞减少症、高钾血症、低钾血症（2）、血栓形成/栓塞），无4级腹泻或感觉神经病变。奥沙利铂、伊立替康和卡培他滨每周一次给药的新方案确实能诱导晚期胃腺癌和GEJ腺癌的缓解。然而，总的反应率是适度的，并没有比其他方案的改善。
There is no standard first-line therapy for advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma and the prognosis remains poor. Our institution conducted a phase I study of oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule. The regimen was tolerated; pharmacodynamic studies revealed no drug interactions, and there was one confirmed response in a gastric cancer patient. We performed a phase II trial in advanced gastric and GEJ adenocarcinoma to determine response rate and response duration.This was a multi-center single treatment arm study involving six sites. Only prior adjuvant therapy was allowed. Patients had ECOG performance status of 0-2, adequate organ function, and were able to tolerate oral medications. All patients received oxaliplatin 60 mg/m(2) intravenously (IV) and irinotecan 50 mg/m(2) IV weekly times 4 weeks with a 2-week rest period. Capecitabine 450 mg bid orally was received on days 1 through 5 every week for 4 weeks, followed by a 2-week rest. Patients were assessed for response after the first two cycles; response duration, overall survival, and adverse events were also recorded. We estimated an improvement in historical response rate by 30% would have clinical meaning.A total of 39 patients were accrued and all were assessed for toxicity; 30 patients were evaluable for response. The median age was 57.8 years (31-79 years) and 74% were male. Two patients had a complete response, with nine patients achieving a partial response. The total response rate was 28%, with nine patients not evaluable for response. The median response duration was noted at 5.97 months and median overall survival was 8.98 months. There were no grade 5 treatment related events, with all deaths secondary to disease progression. Only five grade 4 events occurred (neutropenia, hyperkalemia, hypokalemia (2), thrombosis/embolism) without grade 4 diarrhea or sensory neuropathy.Oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule does induce responses in advanced gastric and GEJ adenocarcinoma. However, the total response rate is modest and not an improvement over other regimens.