BERLIN (EGMN) – Irinotecan significantly prolonged overall survival, compared with best supportive care in patients with advanced gastric cancer, according to results of the first randomized phase III trial investigating second-line chemotherapy in this setting.

This study is potentially practice changing, as there is no established standard in this setting.

“Second-line chemotherapy should be considered a proven option in advanced gastric cancer,” stated Dr. Peter Thuss-Patience, who presented this abstract on behalf of the Arbeitsgemeinschaft Internische Onkologie at the joint congress of the European Cancer Organization and the European Society for Medical Oncology.

“I think that if chemotherapy can prolong survival in this chemo-resistant group of patients, then results should also translate to patients with longer-lasting remissions after first-line chemotherapy,” added Dr. Thuss-Patience of Charité University Clinic, Berlin.

The value of second-line chemotherapy for patients with metastatic gastric cancer has been unclear, he continued. This study, supported by a grant from Pfizer Inc., represents the first randomized phase III data to compare irinotecan versus best supportive care as second-line therapy. Irinotecan is commonly used as first-line therapy.

The randomized, multicenter, open-label study randomly assigned patients to irinotecan 250 mg/m² every 3 weeks (first cycle), with a dose increase to 350 mg/m² or subsequent cycles if tolerable. All patients had histologically-proven adenocarcinoma of the stomach or gastroesophageal junction. One prior regimen for metastatic disease was allowed. The primary end point was overall survival.

From October 2002 to 2006, only 40 patients were randomized, and the study was stopped because of poor accrual, with 21 patients in the irinotecan arm and 19 in the best supportive care arm. Both arms had similar demographic and disease-related characteristics. The best response to first-line chemotherapy (cisplatin/5-fluorouracil) was similar in the two arms.

A total of 68 cycles of irinotecan were given to 19 patients. Two patients in the irinotecan arm did not receive any chemotherapy because of early deterioration. Escalated doses were possible for 37% of patients in the irinotecan arm. The main toxicities of irinotecan were diarrhea (5/19) and neutropenic fever (2/19).

Among 19 evaluable patients in the irinotecan arm, there were no complete or partial responses, and 11 patients (58%) had stable disease. Progressive disease occurred in eight patients (42%). Tumor-related symptoms improved in 44% of patients treated with irinotecan and 5% in the best supportive care arm.

Among all 40 evaluable patients, median overall survival with irinotecan was 4.0 months versus 2.4 months in the best supportive care arm (P = .023), with a hazard ratio of 0.48 (95% CI 0.25-0.92) for the intention-to-treat population.

Accrual of patients was quite difficult, Dr. Thuss-Patience said. Of 30 centers in Germany, only 10 were able to recruit patients. “In our experience, having a devoted doctor was the key to accrual,” he noted.

He summarized his results as follows: “Despite the small number of included patients, irinotecan clearly prolonged survival compared to best supportive care.

During the discussion of the presentation, the question was raised whether further studies investigating new agents in second-line therapy are still ethically supportable when the comparative arm is best supportive care. Two ongoing trials in this setting have a best supportive care arm, and those results should shed some light on this question.

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柏林(EGMN)——根据第一个针对晚期胃癌病人调查二线化学治疗方法的随机III期试验结果，与最佳支持治疗相比，依立替康明显延长了病人的总体生存期。

 

因为没有针对该类病人的标准治疗方法，所以本研究可能改变目前的临床实践。

 

“针对晚期胃癌，二线化学治疗应被认为是可靠的方法。”在欧洲癌症组织和欧洲医学肿瘤学协会的联席大会上，代表德国内科肿瘤学协会(Arbeitsgemeinschaft Internische Onkologie)陈述该摘要的Peter Thuss-Patience博士说。

 

柏林慈善大学医院(Charité University Clinic)的Thuss-Patience博士说，“我认为，如果该化疗方法可以延长此类化学抵抗人群的生存期，那么结果可以理解为病人可以在一线化疗后病情得到长期的缓解。”

 

二线化疗对于转移性胃癌病人的价值未曾得到了解，他接着说到。本研究(由辉瑞公司赞助)给出了比较依立替康和最佳支持治疗的第一个III期试验数据。

 

本随机、多中心、开放标记、随机试验中，病人每3周接受250 mg/m²依立替康(第一个周期)，增至350 mg/m²，如能耐受，进行下一周期治疗。所有的病人均患组织学上确诊的胃或胃食管交界部腺癌。试验前，允许病人针对转移癌进行治疗。主要治疗终点为总体生存率。

 

从2002年10月到2006年，只有40个病人随机分配入组(21人入依立替康组，19人入最佳支持治疗组)，由于招募病人不足，本研究被迫停止。两组的人口统计学特征和疾病相关特性类似。两组对一线治疗(顺铂/5-FU)的最佳反应也类似。

 

19个病人接受共计68个周期的依立替康治疗。2个依立替康组的病人因病情早期出现恶化，未接受任何化疗。依立替康组中，37%的病人的用药剂量逐步增加。依立替康的主要毒性反应是腹泻(5/19)和中性粒细胞减少性发热(2/19)。

 

在依立替康组19个可评估的病人中，没有出现完全或部分缓解，11个病人(58%)病情稳定，8个病人的病情继续进展。依立替康组44%的病人、最佳支持治疗组5%的病人的肿瘤相关症状得到改善。

 

所有40个病人中，总体中位生存期在依立替康组为4.0个月，在最佳支持治疗组为2.4个月(P = 0.023)，目标治疗人群的风险比为0.48(95%可信限 0.25-0.92)。

 

病人的招募非常困难，Thuss-Patience博士说。在德国的30个中心，只有10个能够募集到病人。“依我们看来，拥有热衷于该研究的医师是招募的关键。”

 

他总结研究结果如下：“尽管纳入人数很少，但与最佳支持治疗相比，依立替康明显延长了病人的总体生存期。”

 

在本报告的讨论阶段，有人问到若继续深入研究二线治疗新药物时，再与最佳治疗做对比在伦理上是否行得通。他提到两个正在进行的试验设立了最佳支持治疗组，其结果也许对解答该问题有所裨益。

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