Phase I/II trial of temsirolimus combined with interferon alfa for advanced renal cell carcinoma Journal Article
| Authors: | Motzer, R. J.; Hudes, G. R.; Curti, B. D.; McDermott, D. F.; Escudier, B. J.; Negrier, S.; Duclos, B.; Moore, L.; O'Toole, T.; Boni, J. P.; Dutcher, J. P. |
| Article Title: | Phase I/II trial of temsirolimus combined with interferon alfa for advanced renal cell carcinoma |
| Abstract: | Purpose: Temsirolimus, an inhibitor of the mammalian target of rapamycin, has single-agent activity against advanced renal cell carcinoma (RCC). A recommended dose and safety profile for the combination of temsirolimus and interferon alfa (IFN) were determined in patients with advanced RCC Patients and Methods: Patients were enrolled onto a multicenter, ascending-dose study of temsirolimus (5, 10, 15, 20, or 25 mg) administered intravenously once a week combined with IFN (6 or 9 million units [MU]) administered subcutaneously three times per week. An expanded cohort was treated at the recommended dose to obtain additional safety and efficacy information. Results: Seventy-one patients were entered to receive one of six dose levels. The recommended dose was temsirolimus 15 mg/IFN 6 MU based on dose-limiting toxicities of stomatitis, fatigue, and nausea/vomiting, which were observed at higher doses of temsirolimus and IFN. The most frequent grade 3 or 4 toxicities occurring in any cycle included leukopenia, hypophosphatemia, asthenia, anemia, and hypertriglyceridemia for all patients and those who received the recommended dose. Among patients who received the recommended dose (n = 39), 8% achieved partial response and 36% had stable disease for at least 24 weeks. Median progression-free survival for all patients in the study was 9.1 months. Conclusion: The combination of temsirolimus and IFN has an acceptable safety profile and displays antitumor activity in patients with advanced RCC. Temsirolimus 15 mg plus IFN 6 MU is the recommended dose for evaluation in a randomized phase III study. © 2007 by American Society of Clinical Oncology. |
| Keywords: | adult; controlled study; aged; aged, 80 and over; disease-free survival; middle aged; major clinical study; clinical trial; fatigue; neutropenia; advanced cancer; area under the curve; diarrhea; dose response; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypophosphatemia; recommended drug dose; alpha interferon; disease free survival; antineoplastic agent; anorexia; alpha2b interferon; phase 2 clinical trial; anemia; leukopenia; stomatitis; thrombocytopenia; antineoplastic combined chemotherapy protocols; myalgia; drug administration schedule; analytic method; cohort analysis; antineoplastic activity; dose-response relationship, drug; kidney carcinoma; kidney neoplasms; temsirolimus; arthralgia; asthenia; chill; coughing; drug dose escalation; drug hypersensitivity; dyspnea; hyperglycemia; lymphocytopenia; pneumonia; rash; blood; kidney tumor; carcinoma, renal cell; chemically induced disorder; drug derivative; taste disorder; nausea and vomiting; pleura effusion; area under curve; maximum tolerated dose; phase 1 clinical trial; drug administration; alpha2a interferon; drug dose increase; epistaxis; rapamycin; sirolimus; hypertriglyceridemia; respiratory tract disease; interferon-alpha; exanthema; digestive system diseases; digestive system disease; respiratory tract diseases |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 25 |
| Issue: | 25 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2007-09-01 |
| Start Page: | 3958 |
| End Page: | 3964 |
| Language: | English |
| DOI: | 10.1200/jco.2006.10.5916 |
| PUBMED: | 17761980 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 56" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus" |
