Neoadjuvant cisplatinum based combination chemotherapy in patients with invasive bladder cancer: a combined analysis of two Nordic studies.
OBJECTIVE
A Nordic collaborative group assessed the effectiveness of cisplatinum based combination chemotherapy prior to cystectomy in two consecutive trials. We analyzed overall survival in all patients and in prespecified subgroups defined by preoperative T-stage, gender and age.


METHODS
The studies included in 1985-1997 620 patients with clinically T1G3, T2-T4aNXM0 urothelial bladder cancer and WHO performance </=2. Platinum was combined with adriamycin in the first and with methotrexate in the second trial. In the first of the studies, preoperative radiotherapy was used in both arms. Individual patient data were used. No patients were lost to follow-up. The median follow-up was 4.7 years. A fixed effect model was used to combine the results of the two trials. Subgroup analyses were performed for T-stages, gender and age groups. All analyses were done according to intention to treat.


RESULTS
The combined study results showed a hazard ratio of 0.80 (95% confidence interval 0.64-0.99) for overall survival in favor of neoadjuvant treatment. Survival was 56% at five years in the experimental group versus 48% in the control group, thus corresponding to an eight percent absolute risk reduction after neoadjuvant chemotherapy. We could not substantiate any differences in effect by subgroup.


CONCLUSIONS
In a combined analysis of two trials within the same study organization and the same clinical and biological domain, neoadjuvant platinum based combination chemotherapy was associated with a 20% reduction in the relative hazard in probability of death.
Sherif
Amir
A
Department of Urology, Akademiska University Hospital, SE-751 85 Uppsala, Sweden. amir.sherif@swipnet.se
Holmberg
Lars
L
Rintala
Erkki
E
Mestad
Oddvar
O
Nilsson
Jonas
J
Nilsson
Sten
S
Malmström
Per-Uno
PU
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000008:administration & dosage; D015653:Cystectomy; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D016032:Randomized Controlled Trials as Topic; D012537:Scandinavian and Nordic Countries; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery
D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate