Randomized phase II trial of sunitinib on an intermittent versus continuous dosing schedule as first-line therapy for advanced renal cell carcinoma Journal Article
| Authors: | Motzer, R. J.; Hutson, T. E.; Olsen, M. R.; Hudes, G. R.; Burke, J. M. ; Edenfield, W. J.; Wilding, G.; Agarwal, N.; Thompson, J. A.; Cella, D.; Bello, A.; Korytowsky, B.; Yuan, J.; Valota, O.; Martell, B.; Hariharan, S.; Figlin, R. A. |
| Article Title: | Randomized phase II trial of sunitinib on an intermittent versus continuous dosing schedule as first-line therapy for advanced renal cell carcinoma |
| Abstract: | Purpose: Sunitinib has shown antitumor activity with a manageable safety profile as metastatic renal cell carcinoma (RCC) treatment, when given by the standard intermittent schedule as well as a continuous daily dosing (CDD) schedule. A trial was conducted to compare the schedules. Patients and Methods: Patients with treatment-naive, clear cell advanced RCC were randomly assigned 1:1 to receive sunitinib 50 mg/d for 4 weeks followed by 2 weeks off treatment (schedule 4/2; n = 146) or 37.5 mg/d on the CDD schedule (n = 146) for up to 2 years. The primary end point was time to tumor progression. Results: Median time to tumor progression was 9.9 months for schedule 4/2 and 7.1 months for the CDD schedule (hazard ratio, 0.77;95%CI, 0.57 to 1.04; P=.090). No significant difference was observed in overall survival (23.1 v 23.5 months; P = .615), commonly reported adverse events, or patient-reported kidney cancer symptoms. Schedule 4/2 was statistically superior to CDD in time to deterioration, a composite end point of death, progression, and disease-related symptoms (P = .034). Conclusion: There was no benefit in efficacy or safety for continuous dosing of sunitinib compared with the approved 50 mg/d dose on schedule 4/2. Given the numerically longer time to tumor progression with the approved 50 mg/d dose on schedule 4/2, adherence to this dose and schedule remains the treatment goal for patients with advanced RCC. © 2012 by American Society of Clinical Oncology. |
| Keywords: | survival; adult; controlled study; human tissue; treatment outcome; aged; aged, 80 and over; disease-free survival; middle aged; survival analysis; human cell; major clinical study; overall survival; clinical trial; constipation; fatigue; mortality; sunitinib; advanced cancer; cancer growth; diarrhea; dose response; drug dose comparison; drug efficacy; drug safety; hypertension; side effect; treatment duration; comparative study; disease free survival; cancer staging; neoplasm staging; anorexia; controlled clinical trial; phase 2 clinical trial; mucosa inflammation; nausea; randomized controlled trial; vomiting; proportional hazards models; dehydration; drug administration schedule; continuous infusion; pathology; dose-response relationship, drug; kidney carcinoma; kidney neoplasms; risk assessment; pneumonia; rash; drug fatality; symptom; adverse outcome; proportional hazards model; kidney tumor; carcinoma, renal cell; laboratory test; dosage schedule comparison; multicenter study; pleura effusion; intestine perforation; maximum tolerated dose; kaplan meier method; drug administration; indoles; pyrroles; drug dose regimen; dyspepsia; hand foot syndrome; administration, oral; indole derivative; brain hemorrhage; heart arrest; pyrrole derivative; dysgeusia; oral drug administration; randomized controlled trial (topic); phase 2 clinical trial (topic); kaplan-meier estimate; demyelination; n deethylsunitinib; continuous daily dosing; intermittent schedule; ischemic cardiomyopathy |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 30 |
| Issue: | 12 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2012-04-20 |
| Start Page: | 1371 |
| End Page: | 1377 |
| Language: | English |
| DOI: | 10.1200/jco.2011.36.4133 |
| PROVIDER: | scopus |
| PUBMED: | 22430274 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 24 August 2012" - "CODEN: JCOND" - "Source: Scopus" |
