A Bamias1, K Tzannis2, L C Harshman3, S J Crabb4, Y-N Wong5, S Kumar Pal6, U De Giorgi7, S Ladoire8, N Agarwal9, E Y Yu10, G Niegisch11, A Necchi12, C N Sternberg13, S Srinivas14, A Alva15, U Vaishampayan16, L Cerbone13, M Liontos2, J Rosenberg17, T Powles18, J Bellmunt3, M D Galsky19. 1. Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: abamias@med.uoa.gr. 2. Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. 3. Dana-Farber Cancer Institute, Boston, USA. 4. University of Southampton, Southampton, UK. 5. Fox Chase Cancer Center, Philadelphia. 6. City of Hope Comprehensive Cancer Center, Duarte, USA. 7. IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy. 8. Center Georges-François Leclerc, Dijon, France. 9. University of Utah, Salt Lake City. 10. University of Washington, Seattle, USA. 11. Department of Urology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany. 12. Fondazione IRCCS Istituto Nazionale dei Tumori, Milano. 13. San Camillo Forlanini Hospital, Rome, Italy. 14. Stanford University School of Medicine, Stanford. 15. University of Michigan, Ann Arbor. 16. Karmanos Cancer Institute, Detroit. 17. Memorial Sloan-Kettering Cancer Center, New York, USA. 18. Barts Health and the Royal Free NHS Trust, Queen Mary University of London, London, UK. 19. Mount Sinai School of Medicine, Tisch Cancer Institute, New York, USA.
Abstract
Background: Cisplatin-based combination chemotherapy is the standard treatment of advanced urinary tract cancer (aUTC), but 50% of patients are ineligible for cisplatin according to recently published criteria. We used a multinational database to study patterns of chemotherapy utilization in patients with aUTC and determine their impact on survival. Patients and methods: This was a retrospective study of patients with: UTC (bladder, renal pelvis, ureter or urethra); advanced disease (stages T4b and/or N+ and/or M+); urothelial, squamous or adenocarcinoma histology. Primary objective was overall survival (OS). Eligibility-for-cisplatin was defined by Eastern Cooperative Oncology Group performance status ≤ 1, creatinine clearance ≥ 60 ml/min, no hearing loss, no neuropathy and no heart failure. Cox regression multivariate analyses were used to establish independent associations of cisplatin versus noncisplatin-based chemotherapy on OS. Results: 1794 patients treated between 2000 and 2013 at 29 centers were analyzed. Median follow-up was 29.1 months. About 1333 patients (74%) received first-line chemotherapy: the use of first-line chemotherapy was associated with longer OS: [hazard ratio (HR): 1.91, 95% confidence interval (CI): 1.67-2.20]. Type of first-line chemotherapy received was: cisplatin-based 669 (50%), carboplatin-based 399 (30%) and other 265 (20%). Cisplatin use was an independent favorable prognostic factor (HR: 1.54, 95% CI: 1.35-1.77). This benefit was independent of baseline characteristics or comorbidities but was associated with eligibility-for-cisplatin: eligible patients treated with cisplatin lived longer than those who were not (HR: 1.74, 95% CI: 1.36-2.21), while such benefit was not observed among ineligible patients. About 26% of patients who did not receive cisplatin were eligible for this agent. Median OS of ineligible patients was poor irrespective of the chemotherapy used. Conclusions: The importance of applying published criteria of eligibility-for-cisplatin was confirmed in a multinational, real-world setting in aUTC. The reasons for deviations from these criteria set targets to improve adherence. Effective therapies for cisplatin-ineligible patients are needed.
Background: Cisplatin-based combination chemotherapy is the standard treatment of advanced urinary tract cancer (aUTC), but 50% of patients are ineligible for cisplatin according to recently published criteria. We used a multinational database to study patterns of chemotherapy utilization in patients with aUTC and determine their impact on survival. Patients and methods: This was a retrospective study of patients with: UTC (bladder, renal pelvis, ureter or urethra); advanced disease (stages T4b and/or N+ and/or M+); urothelial, squamous or adenocarcinoma histology. Primary objective was overall survival (OS). Eligibility-for-cisplatin was defined by Eastern Cooperative Oncology Group performance status ≤ 1, creatinine clearance ≥ 60 ml/min, no hearing loss, no neuropathy and no heart failure. Cox regression multivariate analyses were used to establish independent associations of cisplatin versus noncisplatin-based chemotherapy on OS. Results: 1794 patients treated between 2000 and 2013 at 29 centers were analyzed. Median follow-up was 29.1 months. About 1333 patients (74%) received first-line chemotherapy: the use of first-line chemotherapy was associated with longer OS: [hazard ratio (HR): 1.91, 95% confidence interval (CI): 1.67-2.20]. Type of first-line chemotherapy received was: cisplatin-based 669 (50%), carboplatin-based 399 (30%) and other 265 (20%). Cisplatin use was an independent favorable prognostic factor (HR: 1.54, 95% CI: 1.35-1.77). This benefit was independent of baseline characteristics or comorbidities but was associated with eligibility-for-cisplatin: eligible patients treated with cisplatin lived longer than those who were not (HR: 1.74, 95% CI: 1.36-2.21), while such benefit was not observed among ineligible patients. About 26% of patients who did not receive cisplatin were eligible for this agent. Median OS of ineligible patients was poor irrespective of the chemotherapy used. Conclusions: The importance of applying published criteria of eligibility-for-cisplatin was confirmed in a multinational, real-world setting in aUTC. The reasons for deviations from these criteria set targets to improve adherence. Effective therapies for cisplatin-ineligible patients are needed.
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