A multicenter phase II study of G17DT immunogen plus irinotecan in pretreated metastatic colorectal cancer progressing on irinotecan

被引:21
作者
Rocha-Lima, Caio Max [1 ]
Marques Junior, Eriberto de Queiroz [1 ]
Bayraktar, Soley [1 ]
Broome, Paul
Weissman, Charles [2 ]
Nowacki, Marek [3 ]
Leslie, Martin [4 ]
Susnerwala, Shabbir [5 ]
机构
[1] Univ Miami Miller, Sch Med, Div Hematol Oncol, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA
[2] NYOH Latham Canc Ctr, Latham, NY USA
[3] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland
[4] Guys & St Thomas Hosp, London SE1 9RT, England
[5] Royal Preston Hosp, Rosemere Canc Ctr, Preston, Lancs, England
关键词
Metastatic colorectal cancer; Irinotecan; G17DT; Immunotherapy; Irinotecan refractory; RANDOMIZED CONTROLLED-TRIAL; 1ST-LINE TREATMENT; PANCREATIC-CANCER; FLUOROURACIL; LEUCOVORIN; OXALIPLATIN; GROWTH; CETUXIMAB; GASTRIN; MONOTHERAPY;
D O I
10.1007/s00280-014-2520-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The G17DT is a novel human immunogen that raises antibodies to the growth factor gastrin 17 (G17). The purpose of this study was to determine the safety and efficacy of G17DT in combination with irinotecan in patients refractory to irinotecan, and to correlate efficacy with anti-G17 immune response. Patients received G17DT immunogen as a single intramuscular injection of 500 mu g at weeks 1, 5, 9, and 26. Irinotecan was administered as an intravenous infusion of 125 mg/m(2) over 90 min starting at week 5. Each cycle of treatment consisted of irinotecan administered once weekly for 4 weeks, followed by a 2-week rest period. Of 161 patients who received G17DT, the best overall tumor response in the intent-to-treat population was complete response 0 (0 %), partial response 3 (3 %), stable disease 32 (32 %), and progressive disease 64 (65 %). Median survival was 217 days. About 94 (62 %) subjects evaluable for antibody titers were anti-G17 responders. Survival was significantly longer for anti-G17 responders compared with non-responders (9.0 vs. 5.6 months; P < 0.001). Toxicity was consistent with irinotecan (diarrhea, nausea, anemia, vomiting, fatigue, constipation, anorexia, and neutropenia) except for injection site reactions (pain 42 %, induration 13 %, edema 11 %, erythema 10 %, and three abscesses) attributed to G17DT in 52 % of the patients. Treatment with G17DT in combination with irinotecan results in an acceptable anti-G17 immune response, which correlated with promising survival activity in patients refractory to irinotecan-based chemotherapy.
引用
收藏
页码:479 / 486
页数:8
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