Phase i study combining treatment with temsirolimus and sunitinib malate in patients with advanced renal cell carcinoma Journal Article
| Authors: | Patel, P. H.; Senico, P. L.; Curiel, R. E.; Motzer, R. J. |
| Article Title: | Phase i study combining treatment with temsirolimus and sunitinib malate in patients with advanced renal cell carcinoma |
| Abstract: | Purpose: Concurrent inhibition of multiple oncogenic signaling pathways might improve the efficacy of anticancer agents and abrogate resistance mechanisms. This phase I study evaluated temsirolimus in combination with sunitinib in patients with advanced RCC. Patients and Methods: Eligibility included advanced RCC and ≤ 2 previous systemic regimens. At the starting dose, temsirolimus 15 mg was administered by intravenous (I.V.) infusion once weekly, and sunitinib 25 mg was administered orally once daily for 4 weeks, followed by a 2-week rest period. Results: In the first cohort, dose-limiting toxicities (grade 3 treatment-related toxicities that lasted ≥ 7 days) were observed in 2 of 3 patients. One patient experienced grade 3 rash during week 3, which led to treatment discontinuation. A second patient had grade 3 thrombocytopenia (platelet count, 48,000/μL), cellulitis, and gout during week 3 and was hospitalized; platelets recovered to 109,000/μL 4 days after discontinuation of protocol therapy. A third patient experienced rash, asthenia, diarrhea, stomatitis, constipation, fever, and rectal hemorrhage, all of which were mild in severity. The study was terminated because of dose-limiting toxicity observed at low starting doses of both agents. Conclusion: Concomitant use of I.V. temsirolimus 15 mg weekly and oral sunitinib 25 mg daily (4 weeks on, 2 weeks off) is not recommended. |
| Keywords: | adult; treatment outcome; aged; middle aged; clinical trial; constipation; case report; bevacizumab; sunitinib; advanced cancer; cancer growth; diarrhea; drug safety; drug withdrawal; antineoplastic agent; drug eruption; thrombocyte; stomatitis; thrombocytopenia; antineoplastic combined chemotherapy protocols; cohort analysis; antineoplastic activity; pathology; kidney carcinoma; kidney neoplasms; nephrectomy; temsirolimus; asthenia; fever; rash; hospitalization; kidney tumor; carcinoma, renal cell; chemically induced disorder; mammalian target of rapamycin; gout; drug derivative; targeted therapy; hospital discharge; phase 1 clinical trial; kidney cancer; indoles; pyrroles; dyspepsia; administration, oral; indole derivative; infusions, intravenous; epistaxis; rapamycin; mucositis; sirolimus; treatment withdrawal; hypertriglyceridemia; intravenous drug administration; pyrrole derivative; drug eruptions; cellulitis; ecchymosis; rectum hemorrhage; oral drug administration |
| Journal Title: | Clinical Genitourinary Cancer |
| Volume: | 7 |
| Issue: | 1 |
| ISSN: | 1558-7673 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2009-01-01 |
| Start Page: | 24 |
| End Page: | 27 |
| Language: | English |
| DOI: | 10.3816/CGC.2009.n.004 |
| PUBMED: | 19213664 |
| PROVIDER: | scopus |
| PMCID: | PMC3740755 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 20" - "Export Date: 30 November 2010" - "Source: Scopus" |
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