title: A phase II trial of sequential chemotherapy with docetaxel and methotrexate followed by gemcitabine and cisplatin for metastatic urothelial cancer.
abstract: Administration of noncross-resistant agents in a sequential fashion may improve outcome by targeting tumor cells with different sensitivity profiles. We evaluated the toxicity and response rate of docetaxel and methotrexate (DM) followed by gemcitabine and cisplatin (GC) in patients with metastatic or unresectable transitional cell carcinoma of the urothelium. Patients received 3 cycles of DM (40 mg/m2 methotrexate on days 1 and 8 and 100 mg/m2 docetaxel on day 8 repeated every 21 days) followed by GC (1000 mg/m2 gemcitabine on days 1 and 8 and 75 mg/m2 cisplatin on day 1 repeated every 21 days). The most common toxicities were hematologic, with grade 3/4 neutropenia and thrombocytopenia observed in 4 and 2 patients, respectively. Four partial responses were observed after DM (4 of 12, 33% response rate) and 6 responses (3 partial response, 3 complete response, 6 of 9, 67% response rate) after GC for an overall response rate of 7 of 13 (54%). Three patients who progressed on DM responded to GC and 3 responders to DM achieved further response to GC. The median overall survival was 13.6 months. Although we do not recommend this particular sequence of chemotherapy for further study, the uncompromised median survival and the ability to salvage responses with GC suggest that testing of novel agents in sequence with GC is a feasible strategy.
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637-1470, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Artz
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.forename: Todd
authors.initials: T
authors.lastname: Zimmerman
authors.forename: Christopher
authors.initials: C
authors.lastname: Ryan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology; D007682:Kidney Pelvis; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D002945:Cisplatin; D008727:Methotrexate; D000093542:Gemcitabine