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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

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
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
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.

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.
advanced urothelial tract transitional cell carcinoma, phase 2, clinical trial, first-line treatment, sunitinib
0302-2838
599-602
Geldart, Thomas
d4abf5e9-c86e-485d-9a0d-e278020cbc2a
Chester, John
c055dcc5-6b69-42e7-a61f-d5043bd3e69b
Casbard, Angela
b459a5a2-036d-4916-b3b7-d4a4e07221cc
Crabb, Simon
bcd1b566-7677-4f81-8429-3ab0e85f8373
Elliott, Tony
494b0d76-db11-4ef0-bbdb-bd023794726a
Protheroe, Andrew
d08720c0-b773-4e6d-9d29-2341dce037a8
Huddart, Robert A.
4491c174-99e7-4cfe-a5c2-845be33405dc
Mead, Graham
8db84dce-bda0-40c2-a9ea-6c51ee9f2a57
Barber, Jim
53cd387a-5812-4cde-808f-7ad8a54a4231
Jones, Robert J.
bd215beb-7527-4479-be9a-b7df94aae7c4
Smith, Joanna
786a37b9-1a40-4f75-b3b1-0be0cb5d5792
Cowles, Robert
31482fd8-4b12-4681-a4a8-d456d34dc4d9
Evans, Jessica
7db17efc-8cd6-4d56-8d43-8239616804ba
Griffiths, Gareth
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
Geldart, Thomas
d4abf5e9-c86e-485d-9a0d-e278020cbc2a
Chester, John
c055dcc5-6b69-42e7-a61f-d5043bd3e69b
Casbard, Angela
b459a5a2-036d-4916-b3b7-d4a4e07221cc
Crabb, Simon
bcd1b566-7677-4f81-8429-3ab0e85f8373
Elliott, Tony
494b0d76-db11-4ef0-bbdb-bd023794726a
Protheroe, Andrew
d08720c0-b773-4e6d-9d29-2341dce037a8
Huddart, Robert A.
4491c174-99e7-4cfe-a5c2-845be33405dc
Mead, Graham
8db84dce-bda0-40c2-a9ea-6c51ee9f2a57
Barber, Jim
53cd387a-5812-4cde-808f-7ad8a54a4231
Jones, Robert J.
bd215beb-7527-4479-be9a-b7df94aae7c4
Smith, Joanna
786a37b9-1a40-4f75-b3b1-0be0cb5d5792
Cowles, Robert
31482fd8-4b12-4681-a4a8-d456d34dc4d9
Evans, Jessica
7db17efc-8cd6-4d56-8d43-8239616804ba
Griffiths, Gareth
7fd300c0-d279-4ff6-842d-aa1f2b9b864d

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 and Griffiths, Gareth (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), 599-602. (doi:10.1016/j.eururo.2014.11.003). (PMID:25465968)

Record type: Article

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.

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.

Other
1-s2.0-S0302283814011774-main.pdf__tid=2a9b525a-8455-11e4-9b8c-00000aacb35d&acdnat=1418646385_320859c5a22662f43247e92fa7884894 - Accepted Manuscript
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More information

Accepted/In Press date: 3 November 2014
e-pub ahead of print date: 20 November 2014
Published date: April 2015
Keywords: advanced urothelial tract transitional cell carcinoma, phase 2, clinical trial, first-line treatment, sunitinib
Organisations: Cancer Sciences, Clinical Trials Unit

Identifiers

Local EPrints ID: 372462
URI: http://eprints.soton.ac.uk/id/eprint/372462
ISSN: 0302-2838
PURE UUID: bcc36fff-ff80-4e82-a593-970cdaebc852
ORCID for Simon Crabb: ORCID iD orcid.org/0000-0003-3521-9064
ORCID for Gareth Griffiths: ORCID iD orcid.org/0000-0002-9579-8021

Catalogue record

Date deposited: 15 Dec 2014 12:27
Last modified: 15 Mar 2024 03:50

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Contributors

Author: Thomas Geldart
Author: John Chester
Author: Angela Casbard
Author: Simon Crabb ORCID iD
Author: Tony Elliott
Author: Andrew Protheroe
Author: Robert A. Huddart
Author: Graham Mead
Author: Jim Barber
Author: Robert J. Jones
Author: Joanna Smith
Author: Robert Cowles
Author: Jessica Evans

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