Vinflunine–gemcitabine versus vinflunine–carboplatin as first-line chemotherapy in cisplatin-unfit patients with advanced urothelial carcinoma: results of an international randomized phase II trial (JASINT1)

Santis, Maria De; Wiechno, Paweł; Bellmunt, Joaquim; Lucas, C.; Su, Wu Chou; Albigès, Laurence; Lin, Chia‐Chi; Senkus, Elżbieta; Fléchon, Aude; Mourey, Loïc; Necchi, Andrea; Loidl, Wolfgang; Retz, Margitta; Vaissière, Nathalie; Culine, Stéphane

doi:10.1093/annonc/mdv609

Cited by 53 publications

(39 citation statements)

References 22 publications

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“…No definite treatment‐related death was recorded, but one patient had fatal pulmonary embolism (unlikely relation to study treatment). Overall, the AEs are in line with previous studies combining vinflunine and other cytotoxic agents .…”

supporting

confidence: 88%

Safety and Activity of Sorafenib in Addition to Vinflunine in Post-Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial

et al. 2018

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Lessons Learned. First trial to report safety and activity of the microtubule inhibitor vinflunine plus the tyrosine kinase inhibitor sorafenib in post‐platinum metastatic urothelial cancer (mUC) patients. A recommended phase II dose was identified for the treatment combination of vinflunine plus sorafenib, with main adverse events including fatigue, febrile neutropenia, neutropenia, hypertension, and hyponatremia. An overall response rate of 41% to second‐line vinflunine plus sorafenib treatment in patients with platinum‐resistant mUC was confirmed. Background. Platinum‐progressive metastatic urothelial carcinoma (mUC) is a clinical challenge. The tyrosine kinase inhibitor sorafenib has demonstrated varied activity in mUC. This trial was designed to examine safety and activity of vinflunine plus sorafenib in mUC. Methods. In addition to standard dose of vinflunine (320 or 280 mg/m 2 ), patients received sorafenib (400, 600, or 800 mg/day), in a 3 + 3 dose‐escalation phase I design. Results. Twenty‐two patients (median age 62.5 years) were included. Five patients received vinflunine 320 mg/m 2 and 17 received 280 mg/m 2 . The maximum tolerated dose (MTD) of sorafenib with vinflunine 280 mg/m 2 was 600 mg, and with vinflunine 320 mg/m 2 it was not determined, owing to toxicity. Adverse events (AEs) grades 3 + 4 consisted of neutropenia (6 patients), febrile neutropenia (5), and hyponatremia (5). The overall response rate (ORR) in the efficacy‐evaluable patients was 41% (7 of 17), all partial responses evaluated by RECIST version 1.1. Median overall survival (OS) was 7.0 months (1.8–41.7). Conclusion. The defined recommended phase II dose (RPTD) was vinflunine 280 mg/m 2 plus sorafenib 400 mg. Sorafenib was too toxic in combination with vinflunine 320 mg/m 2 . The ORR of 41% to this second‐line combination treatment of mUC is noteworthy and supports further trials.

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supporting

confidence: 88%

Safety and Activity of Sorafenib in Addition to Vinflunine in Post-Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial

et al. 2018

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“…Furthermore, the efficacy of vinflunine in second-line treatment has been confirmed in real-world studies [15]. Vinflunine combinations, vinflunine and gemcitabine (VG) versus vinflunine and carboplatin, were explored as first-line treatment for cisplatin-unfit patients in the randomised phase II trial JASINT1 [16], showing promising response rates and survival (ORR 53% with confirmed ORR 44% and mOS 14.0 months in the VG arm), although the trial did not include a non-investigational control arm. Based on available data on vinflunine as second-line treatment in patients with aUC and the potential benefit of vinflunine combination therapy as first-line treatment, we explored the efficacy of VG versus standard chemotherapy with CG in the randomised phase II VINGEM trial in patients with aUC unfit for cisplatin due to renal impairment.…”

Section: Introductionmentioning

confidence: 99%

Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma: A randomised phase II trial (VINGEM)

Holmsten

Jensen

Mouritsen

et al. 2020

European Journal of Cancer

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Background: The present study (VINGEM) is the first randomised trial comparing vinflunine/gemcitabine (VG) to standard carboplatin/gemcitabine (CG) in patients with advanced urothelial carcinoma (aUC) ineligible for treatment with cisplatin. Patients and methods: Patients with aUC, creatinine clearance 30e60 ml/min, performance status 1 and no prior chemotherapy for metastatic disease were randomised to the experimental arm (vinflunine 280 or 250 mg/m 2 day 1, gemcitabine 1000 mg/m 2 days 1 and 8, q21

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“…44 De Santis et al investigated a non-carboplatin regimen, vinlunine-gemcitabine, versus vinfluninecarboplatin in the JASINT1 trial. 45 Both doublets offered similar PFS (5.9 versus 6.1 months respectively) and OS (14 versus 12.8 months)…”

Section: Chemotherapy For Advanced Urothelial Cancermentioning

confidence: 93%

Systemic Chemotherapy for Urothelial Cancer – How to Select Systemic Therapy in Bladder Cancer

Bamias¹,

Dimitriadis²

2017

European Oncology &Amp; Haematology

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Urothelial cancer (UC) has long been recognised as a chemosensitive disease, and systemic chemotherapy plays a crucial role in the management of localised and advanced disease. Unfortunately, there has been a paucity of progress during the last 15 years in this area. Neoadjuvant use of cisplatin-based combinations has shown survival benefit and together with radical cystectomy should constitute the cornerstone of early disease management. Most importantly, Galsky criteria concerning fitness for cisplatin provide a useful tool for clinicians, in order to select patients with substantial benefit from cisplatin-based chemotherapy. Adjuvant chemotherapy may be useful in selected cases, but its wide implementation has to be proved. Recently, the advent of modern immunotherapy seems to offer new effective choices for patients with advanced UC.

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Vinflunine–gemcitabine versus vinflunine–carboplatin as first-line chemotherapy in cisplatin-unfit patients with advanced urothelial carcinoma: results of an international randomized phase II trial (JASINT1)

Cited by 53 publications

References 22 publications

Safety and Activity of Sorafenib in Addition to Vinflunine in Post-Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial

Safety and Activity of Sorafenib in Addition to Vinflunine in Post-Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial

Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma: A randomised phase II trial (VINGEM)

Systemic Chemotherapy for Urothelial Cancer – How to Select Systemic Therapy in Bladder Cancer

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