title: Randomised, open-label, phase II trial of paclitaxel, gemcitabine and cisplatin versus gemcitabine and cisplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium.
abstract: The purpose of the study was to evaluate the antitumor activity and the safety of paclitaxel combined with gemcitabine and cisplatin in patients affected by advanced transitional cell carcinoma of the urothelium (TCC). Eighty-five patients affected by advanced TCC and measurable disease were randomized to receive either paclitaxel at dosage of 70 mg/m2, gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks (GCP) or gemcitabine 1000 mg/m2 on days 1, 8, 15 and cisplatin 70 mg/m2 on day 2 every 4 weeks (GC). All enrolled patients were considered evaluable for response and toxicity (intention to treat). The observed response rate was 43% for GCP and 44% for GC combination, respectively. Median time to treatment failure was 32 weeks for GCP and 26 weeks for GC and overall survival 61 vs 49 weeks, respectively (p-value not significant). Grade 3-4 neutropenia was observed in 49% of patients treated with GCP vs 35% of those treated with GC (P=0.05) and grade 3-4 thrombocytopenia was observed in 36% of GCP treated patients as compared to 21% of those treated with GC (P=0.01). Seven patients over 70 years old or with poor PS were removed from the study: 6 patients from GCP group (2 toxic deaths, 2 grade 4 myelotoxicity and 2 grade 3 asthenia) and 1 from GC group was lost to follow-up after the first cycle. The combination of paclitaxel, gemcitabine and cisplatin is effective in the treatment of TCC. However, the addition of paclitaxel to the combination of gemcitabine plus cisplatin seems to increase toxicity, therefore it seems not suitable for poor PS patients and those over 70 years old. Larger and more powered studies are needed to exactly define the role of paclitaxel in this combination.
authors.affiliation: Operative Unit of Medical Oncology, Oncology Institute of Bari, Via Amendola 209, Bari 70126, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.forename: Enrico
authors.initials: E
authors.lastname: Crucitta
authors.forename: Nicola
authors.initials: N
authors.lastname: Silvestris
authors.forename: G
authors.initials: G
authors.lastname: Rosati
authors.forename: L
authors.initials: L
authors.lastname: Manzione
authors.forename: M
authors.initials: M
authors.lastname: De Lena
authors.forename: S
authors.initials: S
authors.lastname: Palmeri
authors.forename: V
authors.initials: V
authors.lastname: Gebbia
authors.forename: S
authors.initials: S
authors.lastname: Mancarella
authors.forename: A
authors.initials: A
authors.lastname: Sobrero
authors.forename: G
authors.initials: G
authors.lastname: Pezzella
authors.forename: P
authors.initials: P
authors.lastname: Comella
authors.forename: A
authors.initials: A
authors.lastname: Mangiameli
authors.forename: D
authors.initials: D
authors.lastname: Muci
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D019459:Urothelium; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine