Randomized phase II trial of pemetrexed/cisplatin with or without CBP501 in patients with advanced malignant pleural mesothelioma.

Autor: Krug LM; Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA. Electronic address: krugl@mskcc.org., Wozniak AJ; Karmanos Cancer Center, Detroit, MI, USA., Kindler HL; University of Chicago, Chicago, IL, USA., Feld R; Princess Margaret Hospital, Toronto, ON, Canada., Koczywas M; City of Hope Cancer Center, Duarte, CA, USA., Morero JL; Hospital Maria Ferrer, Buenos Aires, Argentina., Rodriguez CP; University of Washington, Seattle, WA, USA., Ross HJ; Mayo Clinic Arizona, Scottsdale, AZ, USA., Bauman JE; University of New Mexico, Albuquerque, NM, USA., Orlov SV; St. Petersburg Medical University, St. Petersburg, Russia., Ruckdeschel JC; Intermountain Healthcare, Salt Lake City, UT, USA., Mita AC; Cedars-Sinai Medical Center, Los Angeles, CA, USA., Fein L; Centro Oncologico de Rosario, Rosario, Argentina., He X; ICON Clinical Research, North Wales, PA, USA., Hall R; ICON Clinical Research, North Wales, PA, USA., Kawabe T; CanBas Co., Ltd., Numazu City, Shizuoka, Japan., Sharma S; Huntsman Cancer Institute, Salt Lake City, UT, USA.
Jazyk: angličtina
Zdroj: Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2014 Sep; Vol. 85 (3), pp. 429-34. Date of Electronic Publication: 2014 Jul 05.
DOI: 10.1016/j.lungcan.2014.06.008
Abstrakt: Background: CBP501, a synthetic duodecapeptide, increases cisplatin influx into tumor cells through an interaction with calmodulin enhancing cisplatin cytotoxicity, and effects cell cycle progression by abrogating DNA repair at the G2 checkpoint. In phase I clinical trials of CBP501 alone or in combination with cisplatin, the most common toxicity was infusion-related urticaria. Activity of CBP501 plus cisplatin was observed in patients with ovarian cancer and mesothelioma, including some patients previously treated with cisplatin.
Methods: Chemotherapy naïve patients with unresectable MPM were stratified by histology and performance status, and randomized 2:1 to pemetrexed/cisplatin plus CBP501 25mg/m(2) IV (Arm A) or pemetrexed/cisplatin alone (Arm B). The primary endpoint was progression free survival (PFS) at 4 months.
Results: 65 patients were randomized, and 63 were treated. Patient characteristics in the two arms were balanced. Based on independent radiology review of the treated population, 25/40 patients (63%) in Arm A and 9/23 (39%) in Arm B had PFS≥4mo; the median PFS was 5.1mo (95% CI, 3.9, 6.5) vs 3.4mo (2.5, 6.7). Median OS was 13.3mo (9.2, 16.3) in Arm A and 12.8 (6.5, 16.1) in Arm B. Adverse events were not different than expected from standard chemotherapy, and comparable in the two arms, aside from infusion reactions which occurred in 70% of patients treated with CBP501.
Conclusions: While this randomized phase II trial met its primary endpoint of PFS at 4 months, other parameters such as response rate and overall survival suggest that the addition of CBP501 does not improve the efficacy of standard chemotherapy for MPM.
(Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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