Geldart, T., Chester, J., Casbard, A., Crabb, S., Elliott, T., Protheroe, A., Huddart, R. A., Mead, G., Barber, J., Jones, R. J., Smith, J., Cowles, R., Evans, J., Griffiths, G. (2015) 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. EUROPEAN UROLOGY, 67 (4). pp. 599-602. ISSN 0302-2838

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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-naive participants were recruited and received up to six 21-d cycles of cisplatin 70 mg/m(2) (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. Patient summary: 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. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Item Type:	Article
Authors (ICR Faculty only):	Huddart, Robert
All Authors:	Geldart, T., Chester, J., Casbard, A., Crabb, S., Elliott, T., Protheroe, A., Huddart, R. A., Mead, G., Barber, J., Jones, R. J., Smith, J., Cowles, R., Evans, J., Griffiths, G.
Additional Information:	ISI Document Delivery No.: CB8VY Times Cited: 1 Cited Reference Count: 9 Geldart, Thomas Chester, John Casbard, Angela Crabb, Simon Elliott, Tony Protheroe, Andrew Huddart, Robert A. Mead, Graham Barber, Jim Jones, Robert J. Smith, Joanna Cowles, Robert Evans, Jessica Griffiths, Gareth Cardiff University The SUCCINCT trial was developed on behalf of the UK National Cancer Research Institute Bladder Cancer Clinical Studies Group and sponsored by Cardiff University. We thank all the participants, the doctors, UK National Institute for Health Research Clinical Research Network Cancer research nurses, and other members of the multidisciplinary teams and research teams who supported this trial at participating centres. We thank members of the independent data monitoring committee (Jeff Evans, Emma Hall, and Ruth Plummer) and the independent trial steering committee (Barry Hancock, John Wagstaff, and Stephen Shepherd) for their oversight of the trial. We also thank Sally Munden and Alison Hogan (trial pharmacists), Philip Bell and Colin Thompson (patient representatives), Lynette Lane (nursing advisor), and Margaret Knowles for their input into the trial management group. 1 ELSEVIER SCIENCE BV AMSTERDAM EUR UROL
Uncontrolled Keywords:	Advanced urothelial tract transitional cell carcinoma Phase 2 Clinical trial First-line treatment Sunitinib BLADDER-CANCER THERAPY
Research teams:	ICR divisions > Radiotherapy and Imaging > Clinical Academic Radiotherapy (Huddart)
Depositing User:	Barry Jenkins
Date Deposited:	26 Mar 2015 16:37
Last Modified:	26 Mar 2015 16:37
URI:	http://publications.icr.ac.uk/id/eprint/13986

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