Phase i trial of sunitinib malate plus interferon-α for patients with metastatic renal cell carcinoma Journal Article
| Authors: | Motzer, R. J.; Hudes, G.; Wilding, G.; Schwartz, L. H.; Hariharan, S.; Kempin, S.; Fayyad, R.; Figlin, R. A. |
| Article Title: | Phase i trial of sunitinib malate plus interferon-α for patients with metastatic renal cell carcinoma |
| Abstract: | Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor that has demonstrated superior efficacy over interferon (IFN)-α in a phase III trial in first-line, metastatic renal cell carcinoma (RCC). Herein, we report the results of a phase I dose-finding study of sunitinib in combination with IFN-α as first-line treatment in patients with metastatic RCC. Patients and Methods: Treatment-naive patients with clear-cell metastatic RCC received sunitinib at a starting dose of 50 mg or 37.5 mg orally once daily in 6-week cycles (schedule 4/2) plus IFN-α at a starting dose of 3 MU subcutaneously 3 times a week, with weekly intrapatient dose escalation to a maximum of 9 MU as tolerated. Patients who did not tolerate either drug received lower doses of either or had dose interruptions. Results: Twenty-five patients were enrolled; their median age was 64 years (range, 45-77 years). All patients experienced grade 3/4 treatment-emergent adverse events; the most common were neutropenia, fatigue, and thrombocytopenia. After a median of 4 cycles (range, 1-9 cycles), 3 patients (12%) had a partial response, and 20 (80%) had stable disease. Conclusion: Although reduced starting doses were tolerated (37.5 mg for sunitinib and 3 MU for IFN-α), even these lower doses might not be well tolerated for long-term treatment of patients with metastatic RCC. Based on historical data, sunitinib on schedule 4/2 appears to be more effective as single-agent therapy. Further study of sunitinib plus IFN-α on this schedule is not being pursued in RCC. |
| Keywords: | adult; controlled study; treatment outcome; aged; middle aged; major clinical study; clinical trial; constipation; drug tolerability; fatigue; neutropenia; paresthesia; sunitinib; cancer combination chemotherapy; diarrhea; drug efficacy; drug safety; hypertension; alpha interferon; antineoplastic agent; anorexia; alpha2b interferon; metastasis; multiple cycle treatment; anemia; leukopenia; stomatitis; thrombocytopenia; antineoplastic combined chemotherapy protocols; myalgia; pathology; kidney carcinoma; kidney neoplasms; arthralgia; chill; dizziness; drug dose escalation; dyspnea; fever; syncope; hypokalemia; karnofsky performance status; kidney tumor; carcinoma, renal cell; heart infarction; multicenter study; chemically induced disorder; nausea and vomiting; targeted therapy; flu like syndrome; headache; phase 1 clinical trial; combination therapy; indoles; pyrroles; dyspepsia; hand foot syndrome; dry skin; indole derivative; epistaxis; drug tolerance; pyrrole derivative; first-line therapy; schedule 4/2; dysgeusia; hypocalcemia; interferon-alpha |
| Journal Title: | Clinical Genitourinary Cancer |
| Volume: | 7 |
| Issue: | 1 |
| ISSN: | 1558-7673 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2009-01-01 |
| Start Page: | 28 |
| End Page: | 33 |
| Language: | English |
| DOI: | 10.3816/CGC.2009.n.005 |
| PUBMED: | 19213665 |
| PROVIDER: | scopus |
| PMCID: | PMC3394091 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 15" - "Export Date: 30 November 2010" - "Source: Scopus" |
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