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

Caio Max Rocha-Lima, Eriberto De Queiroz Marques, Soley Bayraktar, Paul Broome, Charles Weissman, Marek Nowacki, Martin Leslie, Shabbir Susnerwala

Research output: Contribution to journalArticle

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Abstract

Background: 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. Methods: Patients received G17DT immunogen as a single intramuscular injection of 500 μg at weeks 1, 5, 9, and 26. Irinotecan was administered as an intravenous infusion of 125 mg/m2 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. Results: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)479-486
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume74
Issue number3
DOIs
StatePublished - Jan 1 2014

Fingerprint

irinotecan
Colorectal Neoplasms
Refractory materials
Survival
Chemotherapy
Antibodies
Intramuscular Injections
Anorexia
Constipation
Erythema
Neutropenia
Intravenous Infusions
Abscess
Nausea
Vomiting
Fatigue
Toxicity
Anemia
Tumors

Keywords

  • G17DT
  • Immunotherapy
  • Irinotecan
  • Irinotecan refractory
  • Metastatic colorectal cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

Rocha-Lima, C. M., De Queiroz Marques, E., Bayraktar, S., Broome, P., Weissman, C., Nowacki, M., ... Susnerwala, S. (2014). A multicenter phase II study of G17DT immunogen plus irinotecan in pretreated metastatic colorectal cancer progressing on irinotecan. Cancer Chemotherapy and Pharmacology, 74(3), 479-486. https://doi.org/10.1007/s00280-014-2520-y

A multicenter phase II study of G17DT immunogen plus irinotecan in pretreated metastatic colorectal cancer progressing on irinotecan. / Rocha-Lima, Caio Max; De Queiroz Marques, Eriberto; Bayraktar, Soley; Broome, Paul; Weissman, Charles; Nowacki, Marek; Leslie, Martin; Susnerwala, Shabbir.

In: Cancer Chemotherapy and Pharmacology, Vol. 74, No. 3, 01.01.2014, p. 479-486.

Research output: Contribution to journalArticle

Rocha-Lima, CM, De Queiroz Marques, E, Bayraktar, S, Broome, P, Weissman, C, Nowacki, M, Leslie, M & Susnerwala, S 2014, 'A multicenter phase II study of G17DT immunogen plus irinotecan in pretreated metastatic colorectal cancer progressing on irinotecan', Cancer Chemotherapy and Pharmacology, vol. 74, no. 3, pp. 479-486. https://doi.org/10.1007/s00280-014-2520-y
Rocha-Lima, Caio Max ; De Queiroz Marques, Eriberto ; Bayraktar, Soley ; Broome, Paul ; Weissman, Charles ; Nowacki, Marek ; Leslie, Martin ; Susnerwala, Shabbir. / A multicenter phase II study of G17DT immunogen plus irinotecan in pretreated metastatic colorectal cancer progressing on irinotecan. In: Cancer Chemotherapy and Pharmacology. 2014 ; Vol. 74, No. 3. pp. 479-486.
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abstract = "Background: 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. Methods: Patients received G17DT immunogen as a single intramuscular injection of 500 μg at weeks 1, 5, 9, and 26. Irinotecan was administered as an intravenous infusion of 125 mg/m2 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. Results: 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. Conclusion: 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.",
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