title: SUCCINCT: an open-label, single-arm, non-randomised, phase 2 trial of gemcitabine and cisplatin chemotherapy in combination with sunitinib as first-line treatment for patients with advanced urothelial carcinoma.
abstract: Gemcitabine and cisplatin chemotherapy (GC regimen) represents a standard treatment for advanced urothelial carcinoma. We performed an open-label, single-arm, non-randomised, phase 2 trial evaluating the addition of sunitinib to standard GC chemotherapy (SGC regimen). Overall, 63 treatment-naïve participants were recruited and received up to six 21-d cycles of cisplatin 70 mg/m2 (intravenously [IV], day 1) and gemcitabine 1000 mg/m2 (IV, days 1 and 8) combined with sunitinib 37.5 mg (orally, days 2-15). Following review of toxicity after the first six patients, the sunitinib dose was reduced to 25 mg for all patients. Overall response rate was 64%, with response noted in 37 of 58 patients. At 6 mo, 30 of 58 assessable patients (52%; 90% confidence interval [CI], 40-63%) were progression free. Median overall survival was 12 mo (95% CI, 9-15) and was heavily influenced by Bajorin prognostic group. Grade 3-4 toxicities were predominantly haematologic and limited the deliverability of the triple SGC regimen. The trial did not meet its prespecified primary end point of >60% patients progression free at 6 mo. Cumulative myelosuppression led to treatment delays of gemcitabine and cisplatin and dose reduction and/or withdrawal of sunitinib in the majority of cases. The triple-drug combination was not well tolerated. Phase 3 evaluation of the triple SGC regimen in advanced transitional cell carcinoma is not recommended.
  
  
  RESULTS
  The addition of sunitinib to standard cisplatin and gemcitabine chemotherapy was poorly tolerated and did not improve outcomes in advanced urothelial carcinoma. Treatment delivery was limited by myelotoxicity.
authors.affiliation: Royal Bournemouth Hospital, Bournemouth, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Geldart
authors.affiliation: Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK; St James' University Hospital, Leeds, UK.
authors.forename: John
authors.initials: J
authors.lastname: Chester
authors.affiliation: Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, UK. Electronic address: casbardac@cardiff.ac.uk.
authors.forename: Angela
authors.initials: A
authors.lastname: Casbard
authors.affiliation: University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Crabb
authors.affiliation: Christie Hospital, Manchester, UK.
authors.forename: Tony
authors.initials: T
authors.lastname: Elliott
authors.affiliation: Churchill Hospital, Oxford, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Protheroe
authors.affiliation: Institute of Cancer Research and Royal Marsden Hospital, Surrey, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Huddart
authors.affiliation: University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Mead
authors.affiliation: Velindre Cancer Centre, Velindre Hospital, Cardiff, UK.
authors.forename: Jim
authors.initials: J
authors.lastname: Barber
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Jones
authors.affiliation: Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Smith
authors.affiliation: Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Cowles
authors.affiliation: Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Evans
authors.affiliation: Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, UK; University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D001855:Bone Marrow Diseases / Q000139:chemically induced*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D000077210:Sunitinib; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D003841:Deoxycytidine; D002945:Cisplatin; D000077210:Sunitinib; D000093542:Gemcitabine
keywords: Advanced urothelial tract transitional cell carcinoma; Clinical trial; First-line treatment; Phase 2; Sunitinib