Related Experiment Video
Updated: Jun 25, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Phase I study combining treatment with temsirolimus and sunitinib malate in patients with advanced renal cell
Premal H Patel1, Peggy L Senico, Rafael E Curiel
1Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.
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
Results:
In the first cohort, dose-limiting toxicities (grade 3 treatment-related toxicities that lasted >or= 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/microL), cellulitis, and gout during week 3 and was hospitalized; platelets recovered to 109,000/microL 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.
Insights
This phase I trial found that combining intravenous temsirolimus and oral sunitinib in advanced renal cell carcinoma (RCC) led to dose-limiting toxicities. The combination therapy is not recommended due to safety concerns.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Targeting multiple oncogenic pathways may enhance anticancer efficacy and overcome resistance.
- This study investigated the safety and tolerability of combining temsirolimus with sunitinib in advanced renal cell carcinoma (RCC).
Observation:
- A phase I clinical trial enrolled patients with advanced RCC who had received up to two prior systemic regimens.
- The treatment involved intravenous temsirolimus (15 mg weekly) and oral sunitinib (25 mg daily for 4 weeks, followed by a 2-week rest period).
Findings:
- Dose-limiting toxicities were observed in 2 out of 3 patients in the initial cohort, including severe rash and thrombocytopenia.
- One patient required hospitalization due to grade 3 thrombocytopenia, cellulitis, and gout.
- The study was terminated early due to unacceptable toxicity at the tested doses.
Implications:
- The concurrent administration of intravenous temsirolimus and oral sunitinib at the tested doses is not recommended for advanced RCC.
- Further investigation into alternative dosing or combinations may be warranted, but this specific regimen poses significant safety risks.
