A two-cohort phase I study of weekly oxaliplatin and gemcitabine, then oxaliplatin, gemcitabine, and erlotinib during radiotherapy for unresectable pancreatic carcinoma.
A two-cohort phase I study of weekly oxaliplatin and gemcitabine, then oxaliplatin, gemcitabine, and erlotinib during radiotherapy for unresectable pancreatic carcinoma.
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一项两队列 I 期研究，每周使用奥沙利铂和吉西他滨，然后在不可切除的胰腺癌放疗期间使用奥沙利铂、吉西他滨和厄洛替尼。
DOI：
10.1097/coc.0b013e3182467f22
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
O'Neil,BertH
中科院分区：
文献类型：
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作者：
Raftery,Laura;Tepper,JoelE;Goldberg,RichardM;Blackstock,AWilliam;Aklilu,Mebea;Bernard,StephenA;Ivanova,Anastasia;Davies,JanineM;O'Neil,BertH
目的：吉西他滨是一种有效的放射增敏剂。当与标准放射疗法（XRT）组合时，吉西他滨剂量必须减少至其常规剂量的约10%。奥沙利铂和厄洛替尼也具有放射增敏特性。奥沙利铂和吉西他滨已在体外显示出协同作用。我们的目的是确定最大耐受剂量的奥沙利铂和吉西他滨与并行XRT，然后奥沙利铂，吉西他滨，厄洛替尼与XRT在治疗局部晚期和低容量转移性胰腺癌或胆管cancer.Methods：一个修改后的3+ 3剂量递增设计用于测试4个剂量水平的奥沙利铂和吉西他滨给予每周一次，最多6周，每日XRT的分数为1.8戈伊，总剂量为50.4戈伊。剂量限制性毒性（DLT）定义为导致治疗延迟> 1周的任何4级毒性或3级毒性。此外，在一个给定的队列中的3名患者中的2名的剂量减少被计为在修改的3+ 3 design.Results中的剂量递增-递减规则中的DLT：18名患者入组，均患有胰腺癌。队列3中1例患者的4级转氨酶升高导致队列扩展。队列4（最高计划剂量队列）未发生DLT。推荐的II期剂量为奥沙利铂50 mg/m2/wk+吉西他滨200 mg/m2/wk和50.4戈伊XRT。最常见的3级毒性为恶心（22%）、转氨酶升高（17%）、白细胞减少症（17%）和高血糖症（17%）。中位无进展生存期为7.1个月（95%置信区间，4.6-11.1个月），中位总生存期为10.8个月（95%置信区间，7.1-16.7个月）。除了厄洛替尼的耐受性差，在第一个计划的剂量水平，但充分研究的组合受到阻碍的早期关闭的study.Conclusions：每周奥沙利铂50 mg/m2/wk联合吉西他滨200 mg/m2/wk和XRT胰腺癌具有可接受的毒性和有趣的活动。
Objectives:Gemcitabine is a potent radiosensitizer. When combined with standard radiotherapy (XRT) the gemcitabine dose must be reduced to about 10% of its conventional dose. Oxaliplatin and erlotinib also have radiosensitizing properties. Oxaliplatin and gemcitabine have demonstrated synergy in vitro. We aimed to determine the maximum tolerated dose of oxaliplatin and gemcitabine with concurrent XRT, then oxaliplatin, gemcitaibine, and erlotinib with XRT in the treatment of locally advanced and low-volume metastatic pancreatic or biliary cancer.Methods:A modified 3+ 3 dose-escalation design was used for testing 4 dose levels of oxaliplatin and gemcitabine given once weekly for a maximum of 6 weeks with daily XRT in fractions of 1.8 Gy to a total dose of 50.4 Gy. Dose-limiting toxicity (DLT) was defined as any grade 4 toxicity or grade 3 toxicity resulting in a treatment delay of> 1 week. In addition, dose reduction in 2 of the 3 patients in a given cohort was counted as a DLT in dose escalation-deescalation rule in the modified 3+ 3 design.Results:Eighteen patients were enrolled, all with pancreatic cancer. Grade 4 transaminitis in a patient in cohort 3 resulted in cohort expansion. Cohort 4, the highest planned dose cohort, had no DLTs. The recommended phase II dose is oxaliplatin 50 mg/m 2/wk with gemcitabine 200 mg/m 2/wk and 50.4 Gy XRT. The most prevalent grade 3 toxicities were nausea (22%), elevated transaminases (17%), leucopenia (17%), and hyperglycemia (17%). Median progression-free survival was 7.1 months (95% confidence interval, 4.6-11.1 mo) and median overall survival was 10.8 months (95% confidence interval, 7.1-16.7 mo). The addition of erlotinib was poorly tolerated at the first planned dose level, but full study of the combination was hindered by early closure of the study.Conclusions:Weekly oxaliplatin 50 mg/m 2/wk combined with gemcitabine 200 mg/m 2/wk and XRT for pancreatic cancer has acceptable toxicity and interesting activity.