完全切除胃癌的辅助化疗：由GOIRC开展的一项随机III期试验

Adjuvant chemotherapy in completely resected gastric cancer: a randomized phase III trial conducted by GOIRC.

作者信息

Di Costanzo Francesco, Gasperoni Silvia, Manzione Luigi, Bisagni Giancarlo, Labianca Roberto, Bravi Stefano, Cortesi Enrico, Carlini Paolo, Bracci Raffaella, Tomao Silverio, Messerini Luca, Arcangeli Annarosa, Torri Valter, Bilancia Domenico, Floriani Irene, Tonato Maurizio, Dinota Angelo, Strafiuso Gennaro, Corgna Enrichetta, Porrozzi Stella, Boni Corrado, Rondini Ermanno, Giunta Alessandro, Monzio Compagnoni Barbara, Biagioni Franco, Cesari Maurizio, Fornarini Giuseppe, Nelli Fabrizio, Carboni Manlio, Cognetti Francesco, Enzo Maria Ruggeri, Piga Andrea, Romiti Adriana, Olivetti Alessandra, Masoni Luigi, De Stefanis Marinella, Dalla Mola Angelo, Camera Salvatore, Recchia Francesco, De Filippis Sandro, Scipioni Loreto, Zironi Sandra, Luppi Gabriele, Italia Maurizio, Banducci Stefano, Pisani Leretti Andrea, Massidda Bruno, Ionta Maria Teresa, Nicolosi Angelo, Canaletti Rodolfo, Biscottini Bruno, Grigniani Fausto, Di Costanzo Federica, Rovei Rossella, Croce Enrico, Carroccio Rosalia, Gilli Germana, Cavalli Carla, Olgiati Angelo, Pandolfi Umberto, Rossetti Riccardo, Natalini Giovanni, Foa Paolo, Oldani Sabina, Bruno Lorenzo, Cascinu Stefano, Catalano Giuseppina, Catalano Vincenzo, Lungarotti Ferdinando, Farris Antonio, Sarobba Maria Giuseppina, Trignano Mario, Muscogiuri Antonio, Francavilla Fontana, Figoli Franco, Leoni Maurizio, Papiani Giorgio, Orselli Gianfranco, Antimi Mauro, Bellini Vincenzo, Cabassi Alessandro, Contu Antonio, Pazzola Antonio, Frignano Mario, Lastraioli Elena, Saggese Matilde, Bianchini Diletta, Antonuzzo Lorenzo, Mela Micol, Camisa Roberta

机构信息

Unit of Medical Oncology, Azienda Ospedaliero Universitaria Careggi, Viale Pieraccini 17, 50139 Florence, Italy.

出版信息

J Natl Cancer Inst. 2008 Mar 19;100(6):388-98. doi: 10.1093/jnci/djn054. Epub 2008 Mar 11.

DOI:10.1093/jnci/djn054

PMID:18334706

Abstract

BACKGROUND

Complete surgical resection of gastric cancer is potentially curative, but long-term survival is poor.

METHODS

Patients with histologically proven adenocarcinoma of the stomach of stages IB, II, IIIA and B, or IV (T4N2M0) and treated with potentially curative surgery were randomly assigned to follow-up alone or to intravenous treatment with four cycles (repeated every 21 days) of PELF (cisplatin [40 mg/m(2), on days 1 and 5], epirubicin [30 mg/m(2), days 1 and 5], L-leucovorin [100 mg/m(2), days 1-4], and 5-fluorouracil [300 mg/m(2), days 1-4] in a hospital setting. Frequencies and severity of adverse events were determined. Overall survival (OS) and disease-free survival (DFS) were compared between the treatment arms using Kaplan-Meier analysis and a Cox proportional hazards regression model. All statistical tests were two-sided.

RESULTS

From January 1995 through September 2000, 258 patients were randomly assigned to chemotherapy (n = 130) or surgery alone (n = 128). Patient characteristics were well balanced between the two arms. Among those who received chemotherapy, grade 3 or 4 toxic effects including vomiting, mucositis, and diarrhea were experienced by 21.1%, 8.4%, and 11.8% of patients, respectively. Leucopenia, anemia, and thrombocytopenia of grade 3 or 4 were experienced by 20.3%, 3.3%, and 4.2% of patients, respectively. After a median follow-up of 72.8 months, 128 patients (49.6%) experienced recurrence and 139 (53.9%) deaths were observed, one toxicity-related. Relative to treatment with surgery alone, adjuvant chemotherapy did not increase disease-free survival (hazard ratio [HR] of recurrence = 0.92; 95% confidence interval [CI] = 0.66 to 1.27) or overall survival (HR of death = 0.90; 95% CI = 0.64 to 1.26).

CONCLUSIONS

Our results failed to provide proof of an effect of adjuvant chemotherapy with PELF on overall survival or disease-free survival. The estimated effect of chemotherapy (10% reduction in the hazard of death or relapse) is modest and consistent with the results of meta-analyses of adjuvant chemotherapy without platinum agents.

摘要

背景

胃癌的完整手术切除可能治愈疾病，但长期生存率较低。

方法

组织学确诊为IB期、II期、IIIA期、IIIB期或IV期（T4N2M0）胃癌且接受了可能治愈性手术的患者，被随机分配至单纯随访组或接受四个周期（每21天重复一次）PELF方案静脉化疗组（顺铂[40mg/m²，第1天和第5天]、表柔比星[30mg/m²，第1天和第5天]、左亚叶酸钙[100mg/m²，第1 - 4天]、5 - 氟尿嘧啶[300mg/m²，第1 - 4天]），化疗在医院环境中进行。确定不良事件的发生频率和严重程度。采用Kaplan - Meier分析和Cox比例风险回归模型比较治疗组间的总生存期（OS）和无病生存期（DFS）。所有统计检验均为双侧检验。

结果

1995年1月至2000年9月，258例患者被随机分配至化疗组（n = 130）或单纯手术组（n = 128）。两组患者特征均衡。接受化疗的患者中，分别有21.1%、8.4%和11.8%出现3级或4级毒性反应，包括呕吐、黏膜炎和腹泻。分别有20.3%、3.3%和4.2%的患者出现3级或4级白细胞减少、贫血和血小板减少。中位随访72.8个月后，128例患者（49.6%）出现复发，观察到139例（53.9%）死亡，其中1例与毒性反应相关。与单纯手术治疗相比，辅助化疗未提高无病生存期（复发风险比[HR]=0.92；95%置信区间[CI]=0.66至1.27）或总生存期（死亡风险比[HR]=0.90；95%CI = 0.64至1.26）。