Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Gastric Cancer. 2011 Aug;14(3):226-33. doi: 10.1007/s10120-011-0030-8. Epub 2011 Apr 19.
Preclinical studies have shown that mitomycin C (MMC) acts synergistically with irinotecan (CPT-11). In this phase II study, we evaluated the efficacy and toxicity of MMC/CPT-11 therapy as second-line chemotherapy for patients with fluoropyrimidine-resistant advanced gastric cancer.
Eligible patients had evidence of tumor progression despite prior treatment with fluoropyrimidine-based regimens or had relapsed within 6 months after completion of therapy with adjuvant fluoropyrimidines. Treatment consisted of MMC (5 mg/m(2)) and CPT-11 (150 mg/m(2)) administered i.v. every 2 weeks. The primary endpoint was the response rate (RR). Our hypothesis was that this combination therapy was efficacious when the lower boundary of the 95% confidence interval (CI) of the RR exceeded 20% of the threshold RR.
Between April 2002 and July 2003, 45 eligible patients were registered and analyzed. Among the 45 patients, 40 (89%) had previously received chemotherapy for metastasis and 24 (53%) had a performance status (PS) of 0. Thirteen partial responses were obtained among the 45 patients, resulting in an overall RR of 29% (95% CI, 16-42%). The median time to progression was 4.1 months, and the median survival time was 10 months, with a 1-year survival rate of 36%. Grade 4 neutropenia was observed in 29% of the patients, whereas febrile neutropenia occurred in 9%. The incidence rates of grade 3 nausea and diarrhea were 13 and 2%, respectively.
Although this study did not achieve the per-protocol definition of activity, the progression-free survival and overall survival appeared to be promising, with acceptable tolerability. Thus, MMC/CPT-11 therapy as second-line chemotherapy for fluoropyrimidine-resistant advanced gastric cancer presents a potential treatment option in patients with a good PS.
临床前研究表明丝裂霉素 C（MMC）与伊立替康（CPT-11）具有协同作用。在这项 II 期研究中，我们评估了 MMC/CPT-11 治疗作为氟嘧啶耐药晚期胃癌二线化疗的疗效和毒性。
符合条件的患者在接受氟嘧啶类方案治疗后出现肿瘤进展，或在接受辅助氟嘧啶治疗后 6 个月内复发。治疗包括静脉注射 MMC（5mg/m²）和 CPT-11（150mg/m²），每 2 周一次。主要终点是缓解率（RR）。我们的假设是，当 RR 的 95%置信区间（CI）下限超过阈值 RR 的 20%时，该联合治疗是有效的。
2002 年 4 月至 2003 年 7 月，共登记并分析了 45 例符合条件的患者。45 例患者中，40 例（89%）曾接受过转移性化疗，24 例（53%）的表现状态（PS）为 0。45 例患者中有 13 例获得部分缓解，总 RR 为 29%（95%CI，16-42%）。中位无进展生存期为 4.1 个月，中位总生存期为 10 个月，1 年生存率为 36%。中性粒细胞减少症 4 级发生率为 29%，发热性中性粒细胞减少症发生率为 9%。恶心和腹泻 3 级发生率分别为 13%和 2%。
尽管本研究未达到方案定义的活性，但无进展生存期和总生存期似乎很有希望，且耐受性可接受。因此，对于 PS 较好的氟嘧啶耐药晚期胃癌患者，MMC/CPT-11 治疗作为二线化疗具有潜在的治疗选择。
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