Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the urothelium.
Patients with stage IV TCC and no prior systemic chemotherapy were randomized to GC (gemcitabine 1,000 mg/m2 days 1, 8, and 15; cisplatin 70 mg/m2 day 2) or standard MVAC every 28 days for a maximum of six cycles.
Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202). The groups were well-balanced with respect to prognostic factors. Overall survival was similar on both arms (hazards ratio [HR], 1.04; 95% confidence interval [CI], 0.82 to 1.32; P = .75), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89; 95% CI, 0.72 to 1.10), and response rate (GC, 49%; MVAC, 46%). More GC patients completed six cycles of therapy, with fewer dose adjustments. The toxic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MVAC patients had grade 3/4 anemia (27% v 18%, respectively) and thrombocytopenia (57% v 21%, respectively). On both arms, the RBC transfusion rate was 13 of 100 cycles and grade 3/4 hemorrhage or hematuria was 2%; the platelet transfusion rate was four patients per 100 cycles and two patients per 100 cycles on GC and MVAC, respectively. More MVAC patients, compared with GC patients, had grade 3/4 neutropenia (82% v 71%, respectively), neutropenic fever (14% v 2%, respectively), neutropenic sepsis (12% v 1%, respectively), and grade 3/4 mucositis (22% v 1%, respectively) and alopecia (55% v 11%, respectively). Quality of life was maintained during treatment on both arms; however, more patients on GC fared better regarding weight, performance status, and fatigue.
GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to GC.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Aug 10 [Epub]
H von der Maase, S W Hansen, J T Roberts, L Dogliotti, T Oliver, M J Moore, I Bodrogi, P Albers, A Knuth, C M Lippert, P Kerbrat, P Sanchez Rovira, P Wersall, S P Cleall, D F Roychowdhury, I Tomlin, C M Visseren-Grul, P F Conte
From the Aarhus University Hospital, Aarhus; Herlev Hospital, University of Copenhagen, Herlev, Denmark; Northern Centre for Cancer Treatment, Newcastle General Hospital, Newcastle; St Bartholomews Hospital, London, United Kingdom; University of Torino, St Luigi Hospital, Orbassano; Santa Chiara Hospital, Pisa, Italy; The Princess Margaret Hospital, Toronto, Canada; National Institute of Oncology, Budapest, Hungary; Department of Urology, Bonn University, Bonn; Krankenhaus Nordwest, Frankfurt; Klinikum Ludwigshafen, Ludwigshafen, Germany; Centre Eugene Marquis, Rennes, France; Hospital Ciudad De Jaen, Jaen, Spain; Karolinska Hospital, Stockholm, Sweden; and Eli Lilly and Company, Indianapolis, IN.