A phase I study of sunitinib plus capecitabine in patients with advanced solid tumors.

Abstract

PURPOSE:

This open-label, phase I, dose-escalation study assessed the maximum-tolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of sunitinib in combination with capecitabine in patients with advanced solid tumors.

PATIENTS AND METHODS:

Sunitinib (25, 37.5, or 50 mg) was administered orally once daily on three dosing schedules: 4 weeks on treatment, 2 weeks off treatment (Schedule 4/2); 2 weeks on treatment, 1 week off treatment (Schedule 2/1); and continuous daily dosing (CDD schedule). Capecitabine (825, 1,000, or 1,250 mg/m(2)) was administered orally twice daily on days 1 to 14 every 3 weeks for all patients. Sunitinib and capecitabine doses were escalated in serial patient cohorts.

RESULTS:

Seventy-three patients were treated. Grade 3 adverse events included abdominal pain, mucosal inflammation, fatigue, neutropenia, and hand-foot syndrome. The MTD for Schedule 4/2 and the CDD schedule was sunitinib 37.5 mg/d plus capecitabine 1,000 mg/m(2) twice per day; the MTD for Schedule 2/1 was sunitinib 50 mg/d plus capecitabine 1,000 mg/m(2) twice per day. There were no clinically significant pharmacokinetic drug-drug interactions. Nine partial responses were confirmed in patients with pancreatic cancer (n = 3) and breast, thyroid, neuroendocrine, bladder, and colorectal cancer, and cholangiocarcinoma (each n = 1).

CONCLUSION:

The combination of sunitinib and capecitabine resulted in an acceptable safety profile in patients with advanced solid tumors. Further evaluation of sunitinib in combination with capecitabine may be undertaken using the MTD for any of the three treatment schedules.

• Authors: Christopher J Sweeney, E Gabriela Chiorean, Claire F Verschraegen, Fa Chyi Lee, Suzanne Jones, Melanie Royce, Lesley Tye, Katherine F Liau, Akintunde Bello, Richard Chao, Howard A Burris
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 29 Pg. 4513-20 (Oct 10 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20837944 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indoles
• Pyrroles
• Deoxycytidine
• Capecitabine
• Fluorouracil
• Sunitinib

Topics

• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, pharmacokinetics, therapeutic use)
• Area Under Curve
• Capecitabine
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Diarrhea (chemically induced)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Fatigue (chemically induced)
• Female
• Fluorouracil (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Humans
• Indoles (administration & dosage, adverse effects, pharmacokinetics)
• Male
• Metabolic Clearance Rate
• Middle Aged
• Nausea (chemically induced)
• Neoplasms (drug therapy, metabolism, pathology)
• Pyrroles (administration & dosage, adverse effects, pharmacokinetics)
• Sunitinib
• Treatment Outcome
• Vomiting (chemically induced)
• Young Adult