Fractionated radioimmunotherapy with 90Y-clivatuzumab tetraxetan and low-dose gemcitabine is active in advanced pancreatic cancer: A phase 1 trial Article

Ocean, AJ, Pennington, KL, Guarino, MJ et al. (2012). Fractionated radioimmunotherapy with 90Y-clivatuzumab tetraxetan and low-dose gemcitabine is active in advanced pancreatic cancer: A phase 1 trial . CANCER, 118(22), 5497-5506. 10.1002/cncr.27592

cited authors

  • Ocean, AJ; Pennington, KL; Guarino, MJ; Sheikh, A; Bekaii-Saab, T; Serafini, AN; Lee, D; Sung, MW; Gulec, SA; Goldsmith, SJ; Manzone, T; Holt, M; O'Neil, BH; Hall, N; Montero, AJ; Kauh, J; Gold, DV; Horne, H; Wegener, WA; Goldenberg, DM

authors

abstract

  • Background: It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. Methods: Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2-4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m 2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m 2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. Results: Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute's Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at the higher radioimmunotherapy doses. Conclusions: Fractionated radioimmunotherapy with 90Y-hPAM4 and low-dose gemcitabine demonstrated promising therapeutic activity and manageable myelosuppression in patients with advanced pancreatic ductal carcinoma. © 2012 American Cancer Society.

publication date

  • November 15, 2012

published in

Digital Object Identifier (DOI)

start page

  • 5497

end page

  • 5506

volume

  • 118

issue

  • 22