학술논문
Phase II Trial of Carfilzomib Plus Irinotecan in Patients With Small-cell Lung Cancer Who Have Progressed on Prior Platinum-based Chemotherapy.
Document Type
Academic Journal
Author
Arnold SM; University of Kentucky Markey Cancer Center, Lexington, KY; Division of Medical Oncology, Department of Medicine, University of Kentucky, Lexington, KY. Electronic address: susanne.arnold@uky.edu.; Chansky K; Cancer Research and Biostatistics, Seattle, WA.; Baggstrom MQ; Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.; Thompson MA; Aurora Research Institute, Advocate Aurora Health, Milwaukee, WI.; Sanborn RE; Division of Medical Oncology, Providence Cancer Center, Portland, OR.; Villano JL; University of Kentucky Markey Cancer Center, Lexington, KY; Division of Medical Oncology, Department of Medicine, University of Kentucky, Lexington, KY.; Waqar SN; Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.; Hamm J; Norton Cancer Institute, Louisville, KY.; Leggas M; University of Kentucky Markey Cancer Center, Lexington, KY; Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY.; Willis M; Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX.; Rosales J; Department of Internal Medicine, Virginia Mason, Seattle, WA.; Crowley JJ; Cancer Research and Biostatistics, Seattle, WA.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 100893225 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1938-0690 (Electronic) Linking ISSN: 15257304 NLM ISO Abbreviation: Clin Lung Cancer Subsets: MEDLINE
Subject
Language
English
Abstract
Introduction: The purpose of this study was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan (C/I) in patients with relapsed small-cell lung cancer (SCLC).
Patients and Methods: Patients with SCLC who progressed after 1 platinum-containing regimen for recurrent or metastatic disease were eligible. Patients were stratified as: sensitive (SS) (progressive disease > 90 days after chemotherapy) or refractory (RS) (progressive disease 30 to 90 days after chemotherapy) and received up to 6 cycles of C/I; imaging was performed every 2 cycles. The primary endpoint was 6-month overall survival (OS).
Results: All 62 patients enrolled were evaluable for efficacy and adverse events. 6-month OS was 59% in the platinum SS and 54% in the platinum RS. The overall response rate was 21.6% (2.7% complete response, 18.9% partial response) in SS (n = 37) and 12.5% (all partial response) in RS (n = 25). The disease control rate was 68% (SS) and 56% (RS). Progression-free survival and OS were 3.6 months (95% confidence interval [CI], 2.6-4.6 months) and 6.9 months (95% CI, 4.3-12.3 months) in SS, and 3.3 months (95% CI, 1.8-3.9 months) and 6.8 months (95% CI, 4.1-11 months) in RS. Twenty-nine (47%) patients experienced ≥ grade 3 adverse events; 8 (12.9%) subjects had grade 4 toxicities. Three treatment-related deaths occurred: myocardial infarction (possible), lung infection (possible), and sepsis (probable).
Conclusion: In patients with relapsed SCLC, C/I was effective in the treatment of SS and RS. With 4.8% grade 5 toxicity, C/I is a viable option for relapsed patients with SCLC with performance status 0 to 1, particularly in platinum-resistant patients, or subjects who cannot receive immunotherapy.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Patients and Methods: Patients with SCLC who progressed after 1 platinum-containing regimen for recurrent or metastatic disease were eligible. Patients were stratified as: sensitive (SS) (progressive disease > 90 days after chemotherapy) or refractory (RS) (progressive disease 30 to 90 days after chemotherapy) and received up to 6 cycles of C/I; imaging was performed every 2 cycles. The primary endpoint was 6-month overall survival (OS).
Results: All 62 patients enrolled were evaluable for efficacy and adverse events. 6-month OS was 59% in the platinum SS and 54% in the platinum RS. The overall response rate was 21.6% (2.7% complete response, 18.9% partial response) in SS (n = 37) and 12.5% (all partial response) in RS (n = 25). The disease control rate was 68% (SS) and 56% (RS). Progression-free survival and OS were 3.6 months (95% confidence interval [CI], 2.6-4.6 months) and 6.9 months (95% CI, 4.3-12.3 months) in SS, and 3.3 months (95% CI, 1.8-3.9 months) and 6.8 months (95% CI, 4.1-11 months) in RS. Twenty-nine (47%) patients experienced ≥ grade 3 adverse events; 8 (12.9%) subjects had grade 4 toxicities. Three treatment-related deaths occurred: myocardial infarction (possible), lung infection (possible), and sepsis (probable).
Conclusion: In patients with relapsed SCLC, C/I was effective in the treatment of SS and RS. With 4.8% grade 5 toxicity, C/I is a viable option for relapsed patients with SCLC with performance status 0 to 1, particularly in platinum-resistant patients, or subjects who cannot receive immunotherapy.
(Copyright © 2020 Elsevier Inc. All rights reserved.)