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Sorafenib dose escalation in treatment-naïve patients with metastatic renal cell carcinoma: a non-randomised, open-label, Phase 2b study
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Objective: \ud \ud To assess the efficacy and safety of sorafenib dose escalation in metastatic renal cell carcinoma (mRCC).\ud Patients and Methods: \ud \ud Intra-patient dose escalation may enhance the clinical benefit of targeted anticancer agents in metastatic disease. In this non-randomised, open-label, Phase 2b study, treatment-naïve patients with mRCC were initially treated with the standard oral sorafenib dose [400 mg twice daily (BID)]. Two dose escalations were planned, each 200 mg BID after 28 days at the prior level. Dose reductions, interruptions, or delayed escalations were used to manage adverse events (AEs). The primary endpoint was objective response rate (ORR) in the modified intent-to-treat (mITT) population, which comprised patients with ≥6 months of treatment including ≥4 months of therapy at their highest tolerated dose. Secondary endpoints included progression-free survival (PFS) and safety.\ud Results: \ud \ud In all, 83 patients received sorafenib. The dose received for the longest duration was 400, 600, and 800 mg BID in 48.2%, 15.7%, and 24.1% of patients, respectively. The ORR was 44.4% [n = 8/18; 95% confidence interval (CI) 21.5–69.2] and 17.9% (n = 12/67; 95% CI 9.6–29.2) in the mITT and ITT populations, respectively. The median (95% CI) PFS was 7.4 (6.0–11.7) months (ITT). The most common AEs of any grade were hand–foot skin reaction (66.3%) and diarrhoea (63.9%).\ud Conclusion: \ud \ud Sorafenib demonstrated clinical benefit in treatment-naïve patients with mRCC. However, relatively few patients could sustain doses of >400 mg BID. There was evidence that, where tolerated, escalation from the standard sorafenib dose may have enhanced clinical benefit. However, this study does not support dose escalation for most patients with treatment-naïve mRCC. Alternative protocols for sorafenib dose escalation could be explored.
- Subjects :
- Adult
Male
Niacinamide
Sorafenib
Oncology
medicine.medical_specialty
Urology
Population
Phases of clinical research
Antineoplastic Agents
urologic and male genital diseases
Disease-Free Survival
Efficacy
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Clinical endpoint
Humans
030212 general & internal medicine
Progression-free survival
education
Carcinoma, Renal Cell
Aged
Aged, 80 and over
education.field_of_study
Intention-to-treat analysis
business.industry
Phenylurea Compounds
Middle Aged
Kidney Neoplasms
Surgery
Treatment Outcome
Taste disorder
Research Design
030220 oncology & carcinogenesis
Female
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 14644096
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....b164caf0a3105d8373b3646cb0ded14f