CMTTdb

An integrated database for cancer molecular targeted thearpies

Entry Detail


General information
Database:DB00562
Objective:To evaluate the efficacy and safety of gemcitabine and cisplatin in combination with sorafenib, a tyrosinekinase inhibitor, compared with chemotherapy alone as firstline treatment in advanced urothelial cancer.
Authors:Krege S, et al
Title:Prospective randomized doubleblind multicentrephase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUOAB 31/05).
Journal:BJU Int.
Year:2014
PMID:24053564
Trial Design
Clinical Trial Id:NA
Agent:sorafenib
Target:Vascular endothelial growth factor receptor 1
BRaf protooncogene serine/threonineprotein kinase
Protooncogene tyrosineprotein kinase receptor ret
Cancer Type:Urothelial Carcinoma
Cancer Subtype:advanced urothelial cancer
Therapy Type:com
Therapeutic Combination Type:2
Therapeutic Combination Content:gemcitabine and cisplatin plus sorafenib
Study Type:Prospective randomized doubleblind multicentrephase II study
Key Patients Feature:Eligibility criteria for the present study included locallyadvanced (p)T3b, T4 and/or metastatic (N+/M+) TCC of thebladder or upper urinary tract with at least one measurablelesion, according to the Response Evaluation Criteria inSolid Tumors (RECIST) 1.0, and no previous systemicchemotherapy, including neoadjuvant or adjuvant regimens, ortargeted therapies. Previous intravesical chemo, immuno orradiotherapy was required to have been completed for atleast 4 weeks.
Biomarker:NA
Biomark Analysis:NA
Control Group Info:gemcitabine and cisplatin in combination with sorafenib VS chemotherapy alone
Treatment Info:Chemotherapy with gemcitabine (1250 mg/qm on days 1 and 8) and cisplatin (70 mg/qm on day 1) repeated every 21 days, was administered to all patients in a doubleblind randomization of additional sorafenib (400 mg twice daily) vs placebo (two tablets twice daily) on days 321. Treatment continued until progression or unacceptable toxicity, the maximum number of cycles was limited to eight. The response assessment was repeated after every two cycles.
Primary End Point:progression free survival (PFS) of 4.5 months by adding sorafenib to conventional chemotherapy.
Secondary End Point:objective response rate (ORR), overall survival (OS) and toxicity.
Patients Number:132
Trial Results
DLT_MTD:NA
Objective Response Rate:There were no significant differences between the two arms concerning ORR (sorafenib: complete response [CR] 12.5%, partial response [PR] 40%; placebo: CR 12%, PR 35%).
Disease Control Rate:NA
Median Time to Progression:NA
Median PFS A vs. C:sorafenib: 6.3 months, placebo: 6.1 months
Median OS A vs. C:orafenib: 11.3 months, placebo: 10.6 months
Adverse Event(agent arm):Toxicity was moderately higher in the sorafenib arm. Diarrrhoea occurred significantly more often in the sorafenib arm and handfoot syndrome occurred only in the sorafenib arm.
Conclusions:Although the addition of sorafenib to standard chemotherapy showed acceptable toxicity, the trial failed to show a 4.5 months improvement in PFS.