The efficacy and safety of sunitinib given on an individualised schedule as first-line therapy for metastatic renal cell carcinoma: A phase 2 clinical trial.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ administration & dosage
Bone Neoplasms
/ drug therapy
Carcinoma, Renal Cell
/ drug therapy
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug-Related Side Effects and Adverse Reactions
/ prevention & control
Duration of Therapy
Feasibility Studies
Female
Humans
Kidney Neoplasms
/ pathology
Liver Neoplasms
/ drug therapy
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Patient Reported Outcome Measures
Progression-Free Survival
Sunitinib
/ administration & dosage
Survival Rate
Drug dosing biomarker
Kidney neoplasm
Medicine individualised
Sunitinib
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
29
08
2018
revised:
24
11
2018
accepted:
09
12
2018
pubmed:
17
1
2019
medline:
10
5
2020
entrez:
17
1
2019
Statut:
ppublish
Résumé
Sunitinib is administered on a rigid schedule that may not be optimal for all patients. We hypothesised that toxicity-driven dose and schedule changes would optimise drug exposure and outcome for each patient. In a phase 2 trial, 117 patients with metastatic clear cell renal cell cancer were started on sunitinib 50 mg/day with the aim to treat for 28 days. Treatment breaks were reduced to 7 days. Sunitinib dose and the number of days on therapy were individualised based on toxicity aiming for ≤ grade II toxicity with dose escalation in patients with minimal toxicity. The null hypothesis for the primary end-point was a progression-free survival (PFS) of 8.5 months based on a study with similar eligibility criteria. The null hypothesis was rejected (p < 0.001) with a median PFS of 12.5 months (95% confidence interval [CI]: 9.6-16.5). The median overall survival was 38.5 months (95% CI: 28.3-not reached). The objective response rate (46.1%) and stable disease rate (38.5%) translated into a clinical benefit for 84.6% of patients with no decline in quality of life scores during therapy. Fewer patients were dose reduced (26.5% vs. 50%) or discontinued due to toxicity (7.7 vs. 18-20%) compared to standard sunitinib dosing, and 20 (18.4%) patients were dose escalated to 62.5 mg (12) and 75 mg (8) with a wide individual variation in the optimal dose and treatment duration. Individualised sunitinib therapy is feasible, safe and an effective method to manage toxicity with one of the best efficacy seen for oral vascular endothelial growth factor inhibitors in metastatic renal cell carcinoma. CLINICALTRIALS. NCT01499121.
Sections du résumé
BACKGROUND
Sunitinib is administered on a rigid schedule that may not be optimal for all patients. We hypothesised that toxicity-driven dose and schedule changes would optimise drug exposure and outcome for each patient.
MATERIALS AND METHODS
In a phase 2 trial, 117 patients with metastatic clear cell renal cell cancer were started on sunitinib 50 mg/day with the aim to treat for 28 days. Treatment breaks were reduced to 7 days. Sunitinib dose and the number of days on therapy were individualised based on toxicity aiming for ≤ grade II toxicity with dose escalation in patients with minimal toxicity. The null hypothesis for the primary end-point was a progression-free survival (PFS) of 8.5 months based on a study with similar eligibility criteria.
RESULTS
The null hypothesis was rejected (p < 0.001) with a median PFS of 12.5 months (95% confidence interval [CI]: 9.6-16.5). The median overall survival was 38.5 months (95% CI: 28.3-not reached). The objective response rate (46.1%) and stable disease rate (38.5%) translated into a clinical benefit for 84.6% of patients with no decline in quality of life scores during therapy. Fewer patients were dose reduced (26.5% vs. 50%) or discontinued due to toxicity (7.7 vs. 18-20%) compared to standard sunitinib dosing, and 20 (18.4%) patients were dose escalated to 62.5 mg (12) and 75 mg (8) with a wide individual variation in the optimal dose and treatment duration.
CONCLUSIONS
Individualised sunitinib therapy is feasible, safe and an effective method to manage toxicity with one of the best efficacy seen for oral vascular endothelial growth factor inhibitors in metastatic renal cell carcinoma. CLINICALTRIALS.
GOV IDENTIFIER
NCT01499121.
Identifiants
pubmed: 30648632
pii: S0959-8049(18)31552-1
doi: 10.1016/j.ejca.2018.12.006
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Sunitinib
V99T50803M
Banques de données
ClinicalTrials.gov
['NCT01499121']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
69-77Informations de copyright
Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.