Phase I/II trial of sunitinib plus gefitinib in patients with metastatic renal cell carcinoma Journal Article
| Authors: | Motzer, R. J.; Hudes, G. R.; Ginsberg, M. S.; Baum, M. S.; Harmon, C. S.; Kim, S. T.; Chen, I.; Redman, B. G. |
| Article Title: | Phase I/II trial of sunitinib plus gefitinib in patients with metastatic renal cell carcinoma |
| Abstract: | Objectives: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors with proven clinical benefit in patients with metastatic renal cell carcinoma (RCC). This phase I/II study investigated sunitinib in combination with an epidermal growth factor receptor inhibitor, gefitinib, in patients with metastatic RCC. Methods: In phase I, patients received sunitinib 37.5 or 50 mg in 6-week cycles (4 weeks on treatment, 2 off) plus gefitinib 250 mg, both once daily, to determine the sunitinib maximum tolerated dose (MTD). Pharmacokinetics was assessed for both drugs. In phase II, patients received sunitinib MTD plus gefitinib to evaluate the safety and antitumor activity of this combination. Results: Forty-two patients were enrolled: 11 in phase I, and 31 in phase II. In phase I, 2 dose-limiting toxicities were observed with sunitinib 50 mg (grade 2 left ventricular ejection fraction decline and grade 3 fatigue), and 37.5 mg was declared the MTD. Thirteen patients treated at the MTD achieved a partial response (objective response rate: 37%; 95% confidence interval, 22-55) and 12 (34%) had stable disease. Median progression-free survival was 11 months (95% confidence interval, 6-17). The most commonly reported grade 3/4 treatmentrelated adverse event was diarrhea (14%), the only grade 3/4 adverse event to occur in <2 patients. Pharmacokinetic analyses did not indicate any drug-drug interactions. Conclusions: In metastatic RCC, sunitinib plus gefitinib demonstrated comparable efficacy to sunitinib monotherapy with an acceptable safety profile. Dosing, pharmacokinetic profile, and safety support study of sunitinib plus an epidermal growth factor receptor inhibitor in other tumor types. © 2010 by Lippincott Williams & Wilkins. |
| Keywords: | adult; clinical article; controlled study; treatment outcome; aged; disease-free survival; middle aged; survival analysis; clinical trial; drug tolerability; fatigue; sunitinib; area under the curve; cancer combination chemotherapy; drug efficacy; drug safety; drug withdrawal; hypertension; monotherapy; recommended drug dose; side effect; follow-up studies; neoplasm staging; anorexia; biological marker; metastasis; progression free survival; controlled clinical trial; drug eruption; multiple cycle treatment; neutrophil count; phase 2 clinical trial; nausea; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; drug administration schedule; antineoplastic activity; dose-response relationship, drug; renal cell carcinoma; kidney carcinoma; kidney neoplasms; appetite; drug dose escalation; carcinoma, renal cell; acne; gefitinib; erythema; drug blood level; maximum tolerated dose; phase 1 clinical trial; indoles; pyrroles; dyspepsia; hand foot syndrome; administration, oral; dry skin; quinazolines; alopecia; epistaxis; pharmacokinetics; metastatic; dysgeusia |
| Journal Title: | American Journal of Clinical Oncology |
| Volume: | 33 |
| Issue: | 6 |
| ISSN: | 0277-3732 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2010-12-01 |
| Start Page: | 614 |
| End Page: | 618 |
| Language: | English |
| DOI: | 10.1097/COC.0b013e3181c4454d |
| PUBMED: | 20142724 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: AJCOD" - "Source: Scopus" |
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