Guru P Sonpavde1, Luigi Mariani2, Salvatore Lo Vullo2, Daniele Raggi2, Patrizia Giannatempo2, Aristotle Bamias3, Simon J Crabb4, Joaquim Bellmunt5, Evan Y Yu6, Guenter Niegisch7, Ulka N Vaishampayan8, Christine Theodore9, Dominik R Berthold10, Sandy Srinivas11, Srikala S Sridhar12, Elizabeth R Plimack13, Jonathan E Rosenberg14, Thomas Powles15, Matthew D Galsky16, Andrea Necchi17. 1. Dana-Farber Cancer Institute, Boston, Massachusetts. 2. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 3. University of Athens, Athens, Greece. 4. University of Southampton, Southampton. 5. Hospital del Mar Medical Research Institute, Barcelona, Spain. 6. University of Washington, Seattle, Washington. 7. Department of Urology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany. 8. Karmanos Cancer Center, Wayne State University, Detroit, Michigan. 9. Hospital Foch, Suresnes, France. 10. Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 11. Stanford University, Stanford, California. 12. Princess Margaret Hospital Cancer Center, Toronto, Ontario, Canada. 13. Fox Chase Cancer Center, Philadelphia, Pennsylvania. 14. Memorial Sloan Kettering Cancer Center, New York, New York. 15. Barts Cancer Institute, Queen Mary University of London, London, United Kingdom. 16. Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, New York. 17. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: andrea.necchi@istitutotumori.mi.it.
Abstract
PURPOSE: We evaluated the impact of the number of cycles of platinum based, first line chemotherapy (fewer than 6 cycles vs the conventional 6 cycles or more) on the survival of patients with metastatic urothelial carcinoma. MATERIALS AND METHODS: We used the RISC (Retrospective International Study of Invasive/Advanced Cancer of the Urothelium) database. The association of the number of cycles of chemotherapy with overall survival was investigated by Cox multiple regression analysis after controlling for recognized prognostic factors. We excluded patients who received fewer than 3 or more than 9 platinum chemotherapy cycles to reduce confounding factors. The primary analysis was a comparison of overall survival for 3 to 5 vs 6 to 9 cycles using 6-month landmark analysis when 281 death events were observed. RESULTS: Of the 1,020 patients in the RISC 472 received cisplatin or carboplatin, of whom 338 and 134, respectively, were evaluable. A total of 157 patients received 3 to 5 cycles (median 4) and 315 received 6 to 9 cycles (median 6). There was no significant difference in overall survival between 3 to 5 and 6 to 9 cycles (HR 1.02, 95% CI 0.78-1.33, p = 0.91). No significant interactions were observed for the type of platinum (p = 0.09) and completed planned chemotherapy (p = 0.56). The limitations of a hypothesis generating, retrospective analysis applied. CONCLUSIONS: Four cycles of platinum based, first line chemotherapy appeared adequate and did not significantly compromise the survival of patients with advanced urothelial carcinoma. The omission of excessive cycles may avoid unnecessary cumulative toxicity and facilitate a better transition to second line therapy and investigational switch maintenance therapy strategies. These results require prospective validation but they may impact practice in select patients.
PURPOSE: We evaluated the impact of the number of cycles of platinum based, first line chemotherapy (fewer than 6 cycles vs the conventional 6 cycles or more) on the survival of patients with metastatic urothelial carcinoma. MATERIALS AND METHODS: We used the RISC (Retrospective International Study of Invasive/Advanced Cancer of the Urothelium) database. The association of the number of cycles of chemotherapy with overall survival was investigated by Cox multiple regression analysis after controlling for recognized prognostic factors. We excluded patients who received fewer than 3 or more than 9 platinum chemotherapy cycles to reduce confounding factors. The primary analysis was a comparison of overall survival for 3 to 5 vs 6 to 9 cycles using 6-month landmark analysis when 281 death events were observed. RESULTS: Of the 1,020 patients in the RISC 472 received cisplatin or carboplatin, of whom 338 and 134, respectively, were evaluable. A total of 157 patients received 3 to 5 cycles (median 4) and 315 received 6 to 9 cycles (median 6). There was no significant difference in overall survival between 3 to 5 and 6 to 9 cycles (HR 1.02, 95% CI 0.78-1.33, p = 0.91). No significant interactions were observed for the type of platinum (p = 0.09) and completed planned chemotherapy (p = 0.56). The limitations of a hypothesis generating, retrospective analysis applied. CONCLUSIONS: Four cycles of platinum based, first line chemotherapy appeared adequate and did not significantly compromise the survival of patients with advanced urothelial carcinoma. The omission of excessive cycles may avoid unnecessary cumulative toxicity and facilitate a better transition to second line therapy and investigational switch maintenance therapy strategies. These results require prospective validation but they may impact practice in select patients.
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