奥沙利铂、伊立替康和西妥昔单抗治疗晚期胃癌。药物治疗肿瘤工作组（AGMT）的多中心 II 期试验（胃癌-2）。

Oxaliplatin, irinotecan and cetuximab in advanced gastric cancer. A multicenter phase II trial (Gastric-2) of the Arbeitsgemeinschaft Medikamentose Tumortherapie (AGMT).

机构信息

St.Vinzenz Krankenhaus Betriebs GmbH, Sanatoriumstr. 43, A-6511 Zams, Austria.

出版信息

Anticancer Res. 2011 Dec;31(12):4439-43.

PMID:22199312

Abstract

BACKGROUND

Patients suffering from advanced gastric cancer still have a poor prognosis and treatment options are limited. In our previous phase II trial (AGMT-Gastric-1), we showed that the combination of oxaliplatin and irinotecan was well tolerated and effective. The same chemotherapy regimen was now tested in combination with cetuximab in a multicenter phase II trial.

PATIENTS AND METHODS

Oxaliplatin at 85 mg/m(2) biweekly and irinotecan at 125 mg/m(2) biweekly were combined with cetuximab at 400 mg/m(2) loading dose and subsequent weekly infusions of 250 mg/m(2). Fifty-one patients with histologically proven unresectable and/or metastatic gastric adenocarcinoma were treated in the first line setting. The median age was 62 years. A single metastatic site was found in 24 patients, 27 patients had multiple metastatic sites.

RESULTS

Frequently reported adverse events (in more than 20% of patients) were predominantly grade 1 or 2 and included neutropenia (35%), thrombocytopenia (33%), anemia (73%), nausea (45%), diarrhea (57%), alopecia (22%), and fatigue (37%). Grade 3/4 toxicities included neutropenia in 9/1 patients., thrombocytopenia in 1/0 patients, anemia in 3/1 patients, nausea in 2/0 patients, and diarrhea in 7/2 patients. Sensory neuropathy occurred mostly as grade 1 and 2 in 37% of patients, grade 3 neurotoxicity was observed in 7 patients. Acne-like rash grades 1/2/3/4 were reported in 31%/20%/6%/2% of patients respectively. Thirteen patients discontinued the study due to neutropenia (n=5), nausea/vomiting (n=1), diarrhea (n=1), toxic colon (n=2), and allergic reaction to cetuximab at first (n=2), second (n=1) or third infusion (n=1). Thirty-five patients were assessable for response, with 1 patient (3%) showing a complete response, 21 patients (60%) a partial response, 7 patients (20%) a stable disease, and 6 patients (17%) a progressive disease respectively. The median time to progression was 24.8 weeks, median overall survival was 38.1 weeks. All patients tested had a wild type KRAS status.

CONCLUSION

The combination of oxaliplatin and irinotecan with cetuximab is safe and its action established in advanced gastric cancer.

摘要

背景

患有晚期胃癌的患者预后仍然较差，治疗选择有限。在我们之前的 II 期试验（AGMT-Gastric-1）中，我们证明了奥沙利铂和伊立替康的联合应用具有良好的耐受性和疗效。现在，在一项多中心 II 期试验中，我们将相同的化疗方案与西妥昔单抗联合进行了测试。

患者和方法

奥沙利铂 85mg/m²，每两周一次；伊立替康 125mg/m²，每两周一次；西妥昔单抗 400mg/m² 负荷剂量，随后每周输注 250mg/m²。51 例组织学证实不可切除和/或转移性胃腺癌患者在一线治疗中接受了治疗。中位年龄为 62 岁。24 例患者有单一转移部位，27 例患者有多个转移部位。

结果

报告的常见不良反应（超过 20%的患者）主要为 1 级或 2 级，包括中性粒细胞减少（35%）、血小板减少（33%）、贫血（73%）、恶心（45%）、腹泻（57%）、脱发（22%）和疲劳（37%）。3/4 级毒性包括中性粒细胞减少（9/11 例）、血小板减少（1/1 例）、贫血（3/1 例）、恶心（2/0 例）和腹泻（7/2 例）。感觉神经病变主要为 1 级和 2 级，占 37%的患者；7 例患者出现 3 级神经毒性。皮疹分别为 1/2/3/4 级的患者比例为 31%/20%/6%/2%。13 例患者因中性粒细胞减少（n=5）、恶心/呕吐（n=1）、腹泻（n=1）、中毒性结肠炎（n=2）和首次（n=2）、第二次（n=1）或第三次输注（n=1）时对西妥昔单抗过敏而停止研究。35 例患者可评估疗效，1 例（3%）患者完全缓解，21 例（60%）患者部分缓解，7 例（20%）患者疾病稳定，6 例（17%）患者疾病进展。中位无进展生存期为 24.8 周，中位总生存期为 38.1 周。所有检测的患者均为 KRAS 野生型。