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

Autor: Anders Ullén, Fredrik Jäderling, Per Grybäck, Mads Agerbæk, Helle Pappot, Jeffrey Yachnin, C.-H. Shah, H. Von Der Maase, Karin Holmsten
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Oncology
CELL-CARCINOMA
Cancer Research
MULTICENTER
Kaplan-Meier Estimate
THERAPY
Tyrosine-kinase inhibitor
Carboplatin
DOUBLE-BLIND
chemistry.chemical_compound
0302 clinical medicine
PLUS
Antineoplastic Combined Chemotherapy Protocols
030212 general & internal medicine
Chemotherapy-Induced Febrile Neutropenia
Fatigue
Aged
80 and over
Vinflunine
PLACEBO
Middle Aged
Sorafenib
CHEMOTHERAPY
CANCER
030220 oncology & carcinogenesis
Hypertension
Female
Hyponatremia
medicine.drug
Adult
medicine.medical_specialty
Neutropenia
Metastatic Urothelial Carcinoma
Maximum Tolerated Dose
medicine.drug_class
Urology
chemistry.chemical_element
Vinblastine
Young Adult
03 medical and health sciences
Internal medicine
medicine
Carcinoma
Humans
Adverse effect
Aged
Carcinoma
Transitional Cell
business.industry
Clinical Trial Results
medicine.disease
030104 developmental biology
Urinary Bladder Neoplasms
GEMCITABINE
chemistry
Drug Resistance
Neoplasm
Cancer research
Cisplatin
Platinum
business
Febrile neutropenia
Zdroj: Shah, C H, Pappot, H, Agerbæk, M, Holmsten, K, Jäderling, F, Yachnin, J, Grybäck, P, von der Maase, H & Ullén, A 2019, ' Safety and Activity of Sorafenib in Addition to Vinflunine in Post-Platinum Metastatic Urothelial Carcinoma (Vinsor) : Phase I Trial ', Oncologist, vol. 24, no. 6, pp. 745-e213 . https://doi.org/10.1634/theoncologist.2018-0795
The Oncologist
ISSN: 1549-490X
1083-7159
DOI: 10.1634/theoncologist.2018-0795
Popis: 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/m2), 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/m2 and 17 received 280 mg/m2. The maximum tolerated dose (MTD) of sorafenib with vinflunine 280 mg/m2 was 600 mg, and with vinflunine 320 mg/m2 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/m2 plus sorafenib 400 mg. Sorafenib was too toxic in combination with vinflunine 320 mg/m2. The ORR of 41% to this second-line combination treatment of mUC is noteworthy and supports further trials.
Databáze: OpenAIRE
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