Takeuchi Satoshi, Kuroboshi Haruo, Mori Taisuke, Ito Kimihiko, Kondo Eiji, Tabata Tsutomu, Itani Yoshio, Kawaguchi Ryuji, Takeuchi Kyosuke, Soejima Toshinori, Sasaki Ryohei
Department of Obstetrics and Gynecology, National Hospital Organization Kobe Medical Center, Kobe 6540155, Japan.
Division of Gynecologic Oncology, Department of Gynecology, Women Health Care, Kobe Tokushukai Hospital, Kobe 6500017, Japan.
Chin J Cancer Res. 2020 Apr;32(2):218-227. doi: 10.21147/j.issn.1000-9604.2020.02.09.
Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix, but it had not been effective for adenocarcinoma. Concurrent chemoradiotherapy using irinotecan hydrochloride (CPT-11) had been effective for colorectal cancer, thus, we chose CPT-11 as a candidate for gynecologic adenocarcinoma. To evaluate the maximum tolerated dose (MTD) of weekly CPT-11 with external pelvic radiotherapy, a phase 1/2 study was conducted according to modified Fibonacci method.
Eligible patients were advanced uterine cancer with measurable diseases [performance score (PS): 0-2]. Study period was from August 1st, 2002 to December 31st, 2008. The starting dose level (DL) of CPT-11 was 30 mg/m (DL1) given weekly for 4 weeks. Subsequently, dose escalation was scheduled in 10 mg/m increments to 60 mg/m (DL4). The fixed radiotherapy consisted of whole pelvic 1.8 Gy/d, once a day in weekday for five weeks and it amounted to 45 Gy (25 fractions) in total.
Seventeen patients were enrolled. As for toxicities, one (1/17: 5.9%) grade (G) 4 neutropenia lasting 7 days had been seen in DL4. G2 diarrhea was identified in 35.3% (6/17) of the patients, and 11.8% (2/17) G3 diarrhea was observed in DL3 and DL4. Thus, the MTD of CPT-11 was defined as dose of 60 mg/m. The recommended dose was decided as 50 mg/m. The response rate was 88.2% [9 complete response (CR), 3 partial response (PR), 3 stable disease (SD), 2 not evaluable (NE)]. Disease control rate at 1 month after treatment completion was 100% but distant metastases were found in 24% (4/17) in longer outcome.
MTD was 60 mg/m and recommended dose was set as 50 mg/m. This concurrent chemoradiation using weekly CPT-11 was feasible at 50 mg/m, and it might be effective even in adenocarcinoma of the uterus.
顺铂同步放化疗曾被认为是子宫颈鳞状细胞癌的标准治疗方法，但对腺癌无效。盐酸伊立替康（CPT-11）同步放化疗对结直肠癌有效，因此，我们选择CPT-11作为妇科腺癌的候选药物。为评估盆腔外照射放疗时每周使用CPT-11的最大耐受剂量（MTD），根据改良斐波那契方法进行了一项1/2期研究。
符合条件的患者为患有可测量病灶的晚期子宫癌[体能状态评分（PS）：0 - 2]。研究时间为2002年8月1日至2008年12月31日。CPT-11的起始剂量水平（DL）为30 mg/m²（DL1），每周给药1次，共4周。随后，剂量以10 mg/m²的增量递增至60 mg/m²（DL4）。固定放疗方案为全盆腔1.8 Gy/天，工作日每天1次，共5周，总计45 Gy（25次分割）。
共纳入17例患者。关于毒性反应，在DL4观察到1例（1/17：5.9%）4级中性粒细胞减少，持续7天。35.3%（6/17）的患者出现2级腹泻，在DL3和DL4观察到11.8%（2/17）的3级腹泻。因此，CPT-11的MTD定义为60 mg/m²。推荐剂量确定为50 mg/m²。缓解率为88.2%[9例完全缓解（CR），3例部分缓解（PR），3例病情稳定（SD），2例不可评估（NE）]。治疗完成后1个月时的疾病控制率为100%，但在更长时间的随访中发现24%（4/17）发生远处转移。
MTD为60 mg/m²，推荐剂量设定为50 mg/m²。这种每周使用CPT-11的同步放化疗在50 mg/m²时是可行的，甚至对子宫腺癌可能也有效。
