A phase I trial of escalating doses of cixutumumab (IMC-A12) and sorafenib in the treatment of advanced hepatocellular carcinoma

Anthony B. El-Khoueiry, Robert O’Donnell, Thomas J. Semrad, Philip Mack, Suzette Blanchard, Nathan Bahary, Yixing Jiang, Yun Yen, John Wright, Helen Chen, Heinz Josef Lenz, David R. Gandara

研究成果: 雜誌貢獻文章

2 引文 斯高帕斯(Scopus)

摘要

Purpose: The insulin-like growth factor (IGF) pathway is activated in hepatocarcinogenesis. Cixutumumab is a monoclonal antibody against human insulin-like growth factor-1 receptor (IGF-1R). Given the cross-talk between the IGF and VEGF pathways, we performed a phase I study of the combination of cixutumumab and sorafenib in hepatocellular cancer (HCC). Methods: Eligible patients with no prior systemic therapy for advanced HCC and Child–Pugh A to B7 were treated with sorafenib 400 mg BID and escalating doses of cixutumumab (2, 4, or 6 mg/kg IV weekly) in a 3 + 3 design. Dose limiting toxicity (DLT) was defined as treatment-related grade 3 or 4 non-hematologic toxicity (except for a subset of manageable toxicities) or any grade 4 hematologic toxicities. Results: In 21 patients enrolled, there were 3 DLTs; grade 3 hyperglycemia, grade 3 hypophosphatemia, and grade 5 peritonitis. The maximum tolerated dose of cixutumumab was 4 mg/kg IV weekly with standard dose sorafenib. Eighteen of 21 (86%) patients had grade 3 or above toxicities attributed to treatment. One patient also experienced grade 4 colonic perforation and grade 5 peritonitis. The median number of cycles completed was 4 (0–26). Of 16 patients evaluable for response, 81% achieved stable disease. The median progression free survival was 6.0 months (95% CI 3.6–undefined) and the median overall survival was 10.5 months (95% CI 7.1–undefined). Conclusions: While the combination of cixutumumab and sorafenib had a toxicity profile similar to that of sorafenib monotherapy, it manifested limited clinical efficacy in unselected patients with HCC.

原文英語
頁(從 - 到)957-963
頁數7
期刊Cancer Chemotherapy and Pharmacology
81
發行號5
DOIs
出版狀態已發佈 - 五月 1 2018
對外發佈Yes

ASJC Scopus subject areas

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

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    El-Khoueiry, A. B., O’Donnell, R., Semrad, T. J., Mack, P., Blanchard, S., Bahary, N., Jiang, Y., Yen, Y., Wright, J., Chen, H., Lenz, H. J., & Gandara, D. R. (2018). A phase I trial of escalating doses of cixutumumab (IMC-A12) and sorafenib in the treatment of advanced hepatocellular carcinoma. Cancer Chemotherapy and Pharmacology, 81(5), 957-963. https://doi.org/10.1007/s00280-018-3553-4