title: Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours.
abstract: This prospective, randomized study based on two associated trials was designed to evaluate the effect of neoadjuvant chemotherapy with cisplatin and methotrexate with folinic acid rescue or no chemotherapy prior to local treatment in patients with T2-T4b, NX-3, MO transitional cell carcinoma of the bladder. In the first trial, local treatment consisted of cystectomy (DAVECA 8901) and in the other trial the treatment was radiotherapy (DAVECA 8902); 153 eligible patients were randomized. The majority of the patients (89%) completed the protocol. The overall time to progression for all 153 patients was 12.9 months. Median time to progression was 14.2 months with chemotherapy and 11.4 months without chemotherapy. The actuarial 5-year overall survival rate for all 153 patients was 29%, and 29% for both treatment groups. Multivariate analyses showed that T-stage, tumour size and serum creatinine were independent prognostic factors for survival. The cystectomy trial included 33 patients. Median survival was 78.9 months, 82.5 months with chemotherapy and 45.8 months without chemotherapy (p = 0.76). The radiotherapy trial included 120 patients. The median survival was 17.6 months. Median survival was 19.2 months in the group receiving chemotherapy and 16.3 in the group not receiving chemotherapy. The 5-year survival rate was 19% in the group receiving chemotherapy and 24% in the groups not receiving chemotherapy (p = 0.98). Late toxicity grade 3 or 4 of the bladder was recorded in 25% of the patients (actuarial rate). Neoadjuvant chemotherapy with cisplatin and methotrexate did not significantly improve disease-free or overall survival in 153 randomized patients with invasive bladder cancer.
authors.affiliation: Department of Oncology, University Hospital Herlev, Copenhagen, Denmark. lisa.sengelov@dadlnet.dk
authors.forename: Lisa
authors.initials: L
authors.lastname: Sengeløv
authors.forename: Hans
authors.initials: H
authors.lastname: von der Maase
authors.forename: Finn
authors.initials: F
authors.lastname: Lundbeck
authors.forename: Henrik
authors.initials: H
authors.lastname: Barlebo
authors.forename: Hans
authors.initials: H
authors.lastname: Colstrup
authors.forename: Svend Aage
authors.initials: SA
authors.lastname: Engelholm
authors.forename: Torben
authors.initials: T
authors.lastname: Krarup
authors.forename: Ebbe Lindegård
authors.initials: EL
authors.lastname: Madsen
authors.forename: Hans Henrik
authors.initials: HH
authors.lastname: Meyhoff
authors.forename: Søren
authors.initials: S
authors.lastname: Mommsen
authors.forename: Ole Steen
authors.initials: OS
authors.lastname: Nielsen
authors.forename: Dorte
authors.initials: D
authors.lastname: Pedersen
authors.forename: Kenneth
authors.initials: K
authors.lastname: Steven
authors.forename: Bent
authors.initials: B
authors.lastname: Sørensen
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003404:Creatinine / Q000097:blood; D015653:Cystectomy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D015993:Life Tables; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology*; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D011446:Prospective Studies; D011882:Radiotherapy, High-Energy; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery
chemical_list: D015415:Biomarkers; D003404:Creatinine; D002945:Cisplatin; D002955:Leucovorin; D008727:Methotrexate