Patients with metastatic urothelial carcinoma are often ineligible for cisplatin-based treatments. A National Cancer Institute Cancer Therapy Evaluation Program-sponsored trial assessed the tolerability and efficacy of a gemcitabine-eribulin combination in this population.
Patients with treatment-naïve advanced or recurrent metastatic urothelial carcinoma of the bladder, ureter, or urethra not amenable to curative surgery and not candidates for cisplatin-based therapy were eligible. Cisplatin ineligibility was defined as creatinine clearance less than 60 mL/min (but ≥ 30 mL/min), grade 2 neuropathy, or grade 2 hearing loss. Treatment was gemcitabine 1,000 mg/m2 intravenously followed by eribulin 1.4 mg/m2, both on days 1 and 8, repeated in 21-day cycles until progression or unacceptable toxicity. A Simon two-stage phase II trial design was used to distinguish between Response Evaluation Criteria in Solid Tumors, version 1.1 objective response rates of 20% versus 50%.
Between June 2015 and March 2017, 24 eligible patients with a median age of 73 years (range, 62 to 88 years) underwent therapy. Performance status of 0, 1, or 2 was seen in 11, 11, and two patients, respectively. Sites of disease included: lymph nodes, 16; lungs, nine; liver, seven; bladder, five; bones, two. Median number of cycles received was four (range, one to 16). Of 24 patients, 12 were confirmed responders; the observed objective response rate was 50% (95% CI, 29% to 71%). Median overall survival was 11.9 months (95% CI, 5.6 to 20.4 months), and median progression-free survival was 5.3 months (95% CI, 4.5 to 6.7 months). The most common treatment-related any-grade toxicities were fatigue (83% of patients), neutropenia (79%), anemia (63%), alopecia (50%), elevated AST (50%), and constipation, nausea, and thrombocytopenia (42% each).
Gemcitabine-eribulin treatment response and survival for cisplatin-ineligible patients compare favorably to other regimens. Additional research is needed.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 Aug 07 [Epub ahead of print]
Sarmad Sadeghi, Susan G Groshen, Denice D Tsao-Wei, Rahul Parikh, Amir Mortazavi, Tanya B Dorff, Cheryl Kefauver, Christopher Hoimes, Laurence Doyle, David I Quinn, Edward Newman, Primo N Lara
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1University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA., 2University of Kansas, Lawrence, KS., 3The Ohio State University, Columbus, OH., 4City of Hope, Duarte, CA., 5Case Western Reserve University, Cleveland, OH., 6National Cancer Institute, Cancer Therapy Evaluation Program, Bethesda, MD., 7University of California, Davis, Davis, CA.