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

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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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Acknowledgments

The authors wish to thank Thomas Forlenza, MD; Chris Desch, MD; Magdolna Dank, MD; Gyorgy Bodoky, MD; and Katalin Kristo, MD, for patient enrollment to the clinical trial. This research was supported by Aphton Corporation. The current owner of all G17DT-related assets is Cancer Advances Inc. Some of the data were previously presented: Rocha Lima CM, Buck R, Meyer K, Mitrica I, Perkins W, and Michaeli D. A multicenter phase II study of irinotecan in combination with G17DT immunogen in subjects with metastatic colorectal adenocarcinoma (CRC) was refractory to previous irinotecan-based chemotherapy. Abstract published at the 2004 ASCO Annual Meeting, New Orleans, LA, June 5–8, 2004.

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Authors and Affiliations

  1. Sylvester Comprehensive Cancer Center, Divisions of Hematology/Oncology, School of Medicine, University of Miami Miller, 1475 NW 12th Ave St 3300, Miami, FL, 33136, USA

    Caio Max Rocha-Lima, Eriberto de Queiroz Marques Junior & Soley Bayraktar

  2. Mansfield, NG18 1EX, UK

    Paul Broome

  3. NYOH Latham Cancer Center, Latham, NY, USA

    Charles Weissman

  4. Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland

    Marek Nowacki

  5. Guy’s and St Thomas’ Hospital, London, UK

    Martin Leslie

  6. Rosemere Cancer Centre, Royal Preston Hospital, Preston, UK

    Shabbir Susnerwala

Authors
  1. Caio Max Rocha-Lima
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  2. Eriberto de Queiroz Marques Junior
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Correspondence to Caio Max Rocha-Lima.

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Rocha-Lima, C.M., de Queiroz Marques Junior, E., Bayraktar, S. et al. A multicenter phase II study of G17DT immunogen plus irinotecan in pretreated metastatic colorectal cancer progressing on irinotecan. Cancer Chemother Pharmacol 74, 479–486 (2014). https://doi.org/10.1007/s00280-014-2520-y

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  • DOI: https://doi.org/10.1007/s00280-014-2520-y

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