Jatoi Aminah, Tirona Marisa Tria, Cha Steven S, Alberts Steven R, Rowland Kendrith M, Morton Roscoe F, Nair Suresh, Kardinal Carl G, Stella Philip J, Mailliard James A, Sargen Daniel, Goldberg Richard M
Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Int J Gastrointest Cancer. 2002;32(2-3):115-23. doi: 10.1385/ijgc:32:2-3:115.
The incidence of adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia has been rising in the face of limited treatment options for patients with metastatic disease. With the emergence of data to suggest that single agent docetaxel and irinotecan carry antineoplastic effects in this setting, we determined the response rate of these agents when given in combination.
Forty-six patients with metastatic adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia were evaluated. Patients received docetaxel 50 mg/m2/d and irinotecan 130 mg/m2/d intravenously at 21-d intervals with a tumor assessment after 2 cycles. Because of unacceptable toxicity among the first 13 patients, dosing was reduced to docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d intravenously at 21-d intervals.
The response rate for the entire cohort was 26% (95% confidence interval: 14%, 41%) with 12 confirmed partial responses. Five of these 12 responses were observed in patients treated at the higher chemotherapy dose. However, because 8 of 13 patients suffered grade 4 neutropenia and fevers, a dose reduction was incorporated into the protocol, and the remainder of the cohort was treated at the lower dose. All except 4 of the 15 observed grade 4 toxicities occurred at the higher dose, and these toxicities included nausea and vomiting, dyspnea, hypotension, dysrhythmias, and diarrhea in addition to neutropenia and fevers. There were no grade 5 toxicities. The median survival for the entire cohort was 7.3 mo.
The combination of docetaxel and irinotecan provides modest antineoplastic activity among patients with adenocarcinoma of the esophagus, esophagogastric junction, and gastric cardia. Doses of docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d at 21-d intervals provide an acceptable safety profile, but higher doses appear to result in unacceptable toxicity.
面对转移性疾病患者治疗选择有限的情况，食管下三分之一、食管胃交界部和贲门腺癌的发病率一直在上升。随着数据表明单药多西他赛和伊立替康在此种情况下具有抗肿瘤作用，我们确定了这些药物联合使用时的缓解率。
对46例食管下三分之一、食管胃交界部和贲门转移性腺癌患者进行了评估。患者接受多西他赛50mg/m²/天和伊立替康130mg/m²/天静脉注射，每21天为一个周期，2个周期后进行肿瘤评估。由于前13例患者出现不可接受的毒性，剂量减至多西他赛40mg/m²/天和伊立替康100mg/m²/天静脉注射，每21天为一个周期。
整个队列的缓解率为26%（95%置信区间：14%，41%），有12例确诊部分缓解。这12例缓解中有5例出现在接受较高化疗剂量治疗的患者中。然而，由于13例患者中有8例出现4级中性粒细胞减少和发热，方案中纳入了剂量减少措施，队列中的其余患者接受较低剂量治疗。观察到的15例4级毒性中，除4例外均发生在较高剂量时，这些毒性除中性粒细胞减少和发热外，还包括恶心、呕吐、呼吸困难、低血压、心律失常和腹泻。无5级毒性。整个队列的中位生存期为7.3个月。
多西他赛和伊立替康联合使用在食管、食管胃交界部和贲门腺癌患者中具有一定的抗肿瘤活性。多西他赛40mg/m²/天和伊立替康100mg/m²/天每21天为一个周期的剂量提供了可接受的安全性，但较高剂量似乎会导致不可接受的毒性。
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