Ilson David H, Minsky Bruce
Gastrointestinal Oncology Division, Solid Tumor Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Oncology (Williston Park). 2003 Sep;17(9 Suppl 8):32-6.
The limited effectiveness of chemotherapy in esophageal cancer used to palliate metastatic disease or to combine with radiotherapy in locally advanced disease has prompted the evaluation of new systemic agents. Irinotecan (CPT-11, Camptosar) has shown promising activity in a number of gastrointestinal cancers, including esophageal cancer. The phase II evaluation of the combination of weekly irinotecan and cisplatin has shown encouraging response rates exceeding 30% to 50% in esophageal and gastric cancer. Novel regimens include the combination of irinotecan with mitomycin (Mutamycin), the taxanes docetaxel (Taxotere) and paclitaxel, and continuous infusion fluorouracil (5-FU). Irinotecan is an active radiosensitizer, and trials have evaluated the combination of irinotecan with concurrent radiotherapy. We completed a phase I trial combining weekly irinotecan, cisplatin, and concurrent radiotherapy in locally advanced esophageal cancer. Minimal toxicity has been observed, with no grade 3/4 esophagitis or diarrhea, and hematologic toxicity was also surprisingly minimal. Full doses of weekly irinotecan (65 mg/m2) and cisplatin (30 mg/m2) could be combined safely with concurrent radiotherapy, with a significant rate of pathologic complete response. Phase II evaluation of this chemoradiotherapy regimen as preoperative therapy is planned at single institutions and at the cooperative group level in the United States. Further phase I and II investigation of combined irinotecan, cisplatin, and concurrent radiation is ongoing with the addition of targeted agents, including celecoxib (Celebrex), cetuximab (Erbitux), and bevacizumab (Avastin). Alternative combinations of irinotecan with radiotherapy, including the addition of docetaxel and continuous infusion 5-FU, are also undergoing phase I and II evaluation.
化疗在食管癌中用于缓解转移性疾病或与局部晚期疾病的放疗联合使用时效果有限，这促使人们对新的全身治疗药物进行评估。伊立替康（CPT - 11，开普拓）在包括食管癌在内的多种胃肠道癌症中显示出有前景的活性。每周一次伊立替康与顺铂联合方案的II期评估显示，食管癌和胃癌的缓解率令人鼓舞，超过30%至50%。新的方案包括伊立替康与丝裂霉素（丝裂霉素）、紫杉烷类多西他赛（泰索帝）和紫杉醇以及持续输注氟尿嘧啶（5 - FU）的联合。伊立替康是一种有效的放射增敏剂，并且试验评估了伊立替康与同步放疗的联合。我们完成了一项在局部晚期食管癌中每周一次伊立替康、顺铂与同步放疗联合的I期试验。观察到的毒性极小，无3/4级食管炎或腹泻，血液学毒性也出奇地小。每周一次伊立替康（65 mg/m²）和顺铂（30 mg/m²）的全剂量可以与同步放疗安全联合，病理完全缓解率显著。计划在美国的单个机构和协作组层面将这种放化疗方案作为术前治疗进行II期评估。正在进行进一步的I期和II期研究，在联合伊立替康、顺铂和同步放疗中加入靶向药物，包括塞来昔布（西乐葆）、西妥昔单抗（爱必妥）和贝伐单抗（阿瓦斯汀）。伊立替康与放疗的其他联合方案，包括加入多西他赛和持续输注5 - FU，也正在进行I期和II期评估。
