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

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 so...

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Autores principales: Shah, Carl‐Henrik, Pappot, Helle, Agerbæk, Mads, Holmsten, Karin, Jäderling, Fredrik, Yachnin, Jeffrey, Grybäck, Per, von der Maase, Hans, Ullén, Anders
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656519/
https://www.ncbi.nlm.nih.gov/pubmed/30552156
http://dx.doi.org/10.1634/theoncologist.2018-0795
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author Shah, Carl‐Henrik
Pappot, Helle
Agerbæk, Mads
Holmsten, Karin
Jäderling, Fredrik
Yachnin, Jeffrey
Grybäck, Per
von der Maase, Hans
Ullén, Anders
author_facet Shah, Carl‐Henrik
Pappot, Helle
Agerbæk, Mads
Holmsten, Karin
Jäderling, Fredrik
Yachnin, Jeffrey
Grybäck, Per
von der Maase, Hans
Ullén, Anders
author_sort Shah, Carl‐Henrik
collection PubMed
description 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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spelling pubmed-66565192019-07-29 Safety and Activity of Sorafenib in Addition to Vinflunine in Post‐Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial Shah, Carl‐Henrik Pappot, Helle Agerbæk, Mads Holmsten, Karin Jäderling, Fredrik Yachnin, Jeffrey Grybäck, Per von der Maase, Hans Ullén, Anders Oncologist Clinical Trial Results 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. John Wiley & Sons, Inc. 2018-12-14 2019-06 /pmc/articles/PMC6656519/ /pubmed/30552156 http://dx.doi.org/10.1634/theoncologist.2018-0795 Text en © AlphaMed Press; the data published online to support this summary are the property of the authors
spellingShingle Clinical Trial Results
Shah, Carl‐Henrik
Pappot, Helle
Agerbæk, Mads
Holmsten, Karin
Jäderling, Fredrik
Yachnin, Jeffrey
Grybäck, Per
von der Maase, Hans
Ullén, Anders
Safety and Activity of Sorafenib in Addition to Vinflunine in Post‐Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial
title Safety and Activity of Sorafenib in Addition to Vinflunine in Post‐Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial
title_full Safety and Activity of Sorafenib in Addition to Vinflunine in Post‐Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial
title_fullStr Safety and Activity of Sorafenib in Addition to Vinflunine in Post‐Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial
title_full_unstemmed Safety and Activity of Sorafenib in Addition to Vinflunine in Post‐Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial
title_short Safety and Activity of Sorafenib in Addition to Vinflunine in Post‐Platinum Metastatic Urothelial Carcinoma (Vinsor): Phase I Trial
title_sort safety and activity of sorafenib in addition to vinflunine in post‐platinum metastatic urothelial carcinoma (vinsor): phase i trial
topic Clinical Trial Results
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656519/
https://www.ncbi.nlm.nih.gov/pubmed/30552156
http://dx.doi.org/10.1634/theoncologist.2018-0795
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