title: A phase II evaluation of weekly paclitaxel plus carboplatin in advanced urothelial cancer.
abstract: This Phase II trial was designed to evaluate the overall objective response rate, complete response rate, efficacy, and safety of weekly paclitaxel (Taxol) and carboplatin (Paraplatin) in the treatment of advanced urothelial carcinoma. Thirty-three patients with measurable, unresectable, stage III-IV carcinoma of the urothelium were enrolled. Paclitaxel (135 mg/m2) and carboplatin (AUC=2) were given by intravenous (IV) infusion weekly x 6 followed by two weeks rest. Patients were premedicated with oral dexamethasone, diphenhydramine, and cimetadine (or equivalent). Patient characteristics included an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 (36%), one (36%), two (28%); median age 70 years (37-83); 29 (88%) male, four (12%) female; 16 (48%) patients had prior chemotherapy [eight postoperative (adjuvant), five neoadjuvant, three for metastatic disease] and eight (24%) had prior radiation therapy. Eight patients (24%) achieved objective responses, three complete responses (CR) and five partial responses (PR); one patient was not evaluable (patient died prior to first dose). The median duration of response was 13 months (range, 2-29). Nine patients (27%) had stable disease (SD) and 15 patients (45%) had progressive disease (PD). Median time to progression was 3.6 months (range, < 1-29) and median survival was 10.3 months (range, < 1-33). Grade 3 and 4 toxicities included: asthenia (46%), neutropenia (36%), leukopenia (15%), thromboembolism (12%), diarrhea (9%), nausea and vomiting (9%), hyperglycemia (7%), and neuropathy (6%). Two patients died of sepsis, one death was treatment-related. Weekly paclitaxel plus carboplatin shows promising activity; however in the current study, efficacy may have been limited by the toxicities associated with this dose-intensive regimen in an elderly, pretreated patient population with poor performance status. This regimen warrants further study, perhaps as a three out of four week regimen or at reduced doses.
authors.affiliation: US Oncology, Inc., Houston, Texas, USA. friedlandd@msx.upmc.edu
authors.forename: David M
authors.initials: DM
authors.lastname: Friedland
authors.forename: Shaker
authors.initials: S
authors.lastname: Dakhil
authors.forename: Charles
authors.initials: C
authors.lastname: Hollen
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Gregurich
authors.forename: Lina
authors.initials: L
authors.lastname: Asmar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001247:Asthenia / Q000139:chemically induced; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage; D004155:Diphenhydramine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011292:Premedication; D016019:Survival Analysis; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium / Q000473:pathology
chemical_list: D000897:Anti-Ulcer Agents; D003907:Dexamethasone; D004155:Diphenhydramine; D016190:Carboplatin; D017239:Paclitaxel