Clinical Study on the Medical Value of Combination Therapy Involving Adoptive Immunotherapy and Chemotherapy for Stage IV Colorectal Cancer (COMVI Study).
Clinical Study on the Medical Value of Combination Therapy Involving Adoptive Immunotherapy and Chemotherapy for Stage IV Colorectal Cancer (COMVI Study).
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DOI：
10.21873/anticanres.11777
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发表时间：
2017-07
影响因子：
2
通讯作者：
Y. Yoshida;Masayasu Naito;Teppei Yamada;N. Aisu;D. Kojima;T. Mera;Toshihiro Tanaka;Keiko Naito
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文献类型：
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作者：
Y. Yoshida;Masayasu Naito;Teppei Yamada;N. Aisu;D. Kojima;T. Mera;Toshihiro Tanaka;Keiko Naito
通过开发用于产生大量活化的杀伤细胞（如αβ T细胞、γδ T细胞和自然杀伤细胞）的新技术，癌症的免疫疗法已经发展。目前还没有针对IV期结直肠癌的过继免疫治疗和一线化疗联合治疗的前瞻性试验。目前的初步研究旨在评估过继免疫治疗和化疗联合治疗IV期结直肠癌的安全性和可行性（COMVI研究）。患者和方法COMVI研究是一项前瞻性、单组试点试验。每个21天治疗周期中的治疗包括XALIX（第1天130 mg/m2奥沙利铂+第1-14天1，000 mg/m2卡培他滨每日两次）、贝伐珠单抗（第1天7.5 mg/kg）和αβ T淋巴细胞（第18天超过5×109），这些淋巴细胞与固定化抗CD 3抗体和白细胞介素-2体外培养。结果该研究包括2013年6月至2014年9月期间的6名患者（2名男性和4名女性）。患者的中位年龄为68岁（范围=55-75岁）。总缓解率为83.3% [2例完全缓解（33.3%）; 3例部分缓解（50.0%）; 1例疾病稳定（16.7%）;无疾病进展病例]。肿瘤体积缩小率为53%（范围=38.0-100%）。中位无进展生存期和总生存期分别为567天和966天。大多数不良事件的严重程度为轻度至中度，6例患者中未发生4级不良事件。仅1例患者发生3级高血压和肠梗阻。在本研究中，免疫治疗相关毒性极小。结论过继免疫治疗联合化疗治疗IV期结直肠癌是安全可行的。需要II期前瞻性研究来证实这种化学免疫疗法的安全性和有效性。
BACKGROUND Adoptive immunotherapy for cancer has evolved through development of novel technologies for generating a large number of activated killer cells, such as αβ T-cells, γδ T-cells, and natural killer cells. There has been no prospective trial of combination therapy involving adoptive immunotherapy and first-line chemotherapy for stage IV colorectal cancer. The present pilot study aimed to evaluate the safety and feasibility of combination therapy involving adoptive immunotherapy and chemotherapy for stage IV colorectal cancer (COMVI study). PATIENTS AND METHODS The COMVI study was a prospective, single-arm pilot trial. Therapy in each 21-day treatment cycle involved XELOX (130 mg/m2 of oxaliplatin on day 1 plus 1,000 mg/m2 of capecitabine twice daily on days 1-14), bevacizumab (7.5 mg/kg on day 1), and αβ T-lymphocytes (over 5×109 on day 18) cultured ex vivo with an immobilized antibody to CD3 and interleukin-2. RESULTS The study included six patients (two men and four women) between June 2013 and September 2014. The median patient age was 68 years (range=55-75 years). The overall response rate was 83.3% [complete response in two (33.3%); partial response in three (50.0%); stable disease in one (16.7%); no cases of progressive disease]. The tumor volume reduction rate was 53% (range=38.0-100%). The median progression-free and overall survival durations were 567 and 966 days, respectively. Most adverse events were mild-to-moderate in intensity, and no grade 4 adverse events occurred in the six patients. Only one patient experienced grade 3 hypertension and ileus. Immunotherapy-associated toxicity was minimal in this study. CONCLUSION Combination therapy involving adoptive immunotherapy and chemotherapy for stage IV colorectal cancer is feasible and safe. Phase II prospective studies are needed to confirm the safety and efficacy of such chemoimmunotherapy.