过继免疫化疗联合化疗治疗IV期结直肠癌的临床研

Clinical Study on the Medical Value of Combination Therapy Involving Adoptive Immunotherapy and Chemotherapy for Stage IV Colorectal Cancer (COMVI Study)

Yoshida Y1, Naito M2, Yamada T2, Aisu N2, Kojima D2, Mera T2, Tanaka T3, Naito K4, Yasumoto K4, Kamigaki T4, Gotoh S4, Kodama S5, Yamashita Y2, Hasegawa S2.

Anticancer Res. 2017 Jul;37(7):3941-3946.

Abstract

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.

Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

KEYWORDS:

Colorectal cancer; XELOX; bevacizumab; chemotherapy; immunotherapy; αβT