Phase II Study of the Safety and Efficacy of Temsirolimus in East Asian Patients with Advanced Renal Cell Carcinoma†

Abstract

Objective: Temsirolimus, an inhibitor of the mammalian target of rapamycin, is approved for treatment of patients with advanced renal cell carcinoma in the USA and Europe. Temsirolimus was not yet evaluated in East Asian patients. Methods: This non-randomized Phase II study enrolled 82 patients with advanced renal cell carcinoma [20 (24%) Japanese, 30 (37%) Korean and 32 (39%) Chinese patients; median age (range): 55 (26 -83) years]. Most (71%) received prior systemic therapy for metastatic disease; two-thirds were intermediate risk. Six Japanese patients received intravenous temsirolimus 20 mg/m 2 weekly for tolerability assessment (Group A); the remaining 76 received a 25 mg flat dose weekly (Group B). Temsirolimus was dosed once weekly. Primary efficacy end point was the Response Evaluation Criteria in Solid Tumors-defined clinical benefit rate in the intent-to-treat population. Results: In the entire population, regardless of treatment group, the clinical benefit rate was 48% (95% confidence interval: 36, 59). Objective response rate was 11% (95% confidence interval: 5, 20), median progression-free survival was 7.3 months (95% confidence interval: 4.0, 9.2) and median time to treatment failure was 5.4 months (95% confidence interval: 3.5, 7.4). No patient in Group A demonstrated dose-limiting toxicity. The most frequent Grade 3 or 4 drug-related adverse events were anemia, hyperglycemia, hypophosphatemia and stomatitis (5% each). Serious adverse events reported in 5% of patients were pneumonia (9%) and interstitial lung disease (7%). Temsirolimus and its major metabolite, sirolimus, were long-lived throughout the dosage interval, with no evidence of accumulation. Conclusion: Temsirolimus was well tolerated and showed promising activity in Japanese, Korean and Chinese patients with advanced renal cell carcinoma.

Temsirolimus improves cytotoxic efficacy of cisplatin and gemcitabine against urinary bladder cancer cell lines

“…In these studies, the drugs side effects should be taken into consideration. Anemia, hyperglycemia, hypophosphatemia, stomatitis, pneumonia, and interstitial lung disease were already reported on patients with advanced renal cell carcinoma, upon treatment with temsirolimus as a single drug [8].…”

“…In 2012, Sun et al [8] presented a study in which they tested temsirolimus in phase II studies in East Asian patients with advanced RCC, having obtained promising results. This drug has also been used to treat cancer in multiple clinical studies, such as breast cancer [9], glioma [10], endometrial [11], and mantle cell lymphoma [12], as well as in preclinical studies, such as ovarian, lung, colon, breast, and prostate cell lines [13].…”

Incidence and Risk of Treatment-Related Mortality with mTOR Inhibitors Everolimus and Temsirolimus in Cancer Patients: A Meta-Analysis

“…Figure 1 outlined the selection process in detail. These trials represented six studies with temsirolimus [11], [32], [33], [34], [35], [36], and six with everolimus [12], [14], [15], [37], [38], [39]. A total of 3322 patients were available for the meta-analysis, with 1015 patients from temsirolimus trials, and 2307 from everolimus trials.…”

“…A total of 3322 patients were available for the meta-analysis, with 1015 patients from temsirolimus trials, and 2307 from everolimus trials. Four trials were performed in patients with RCC [11], [12], [32], [36], three in patients with breast cancer [14], [33], [38], two in patients with neuroendocrine tumors [15], [39], two in patients with SCLC [35], [37] and one in patients with advanced solid tumors [34]. The 12 included trials were published in 2004–2012.…”

Axitinib versus sorafenib as a second-line therapy in Asian patients with metastatic renal cell carcinoma: results from a randomized registrational study

“…In many countries, the management of metastatic RCC (mRCC) has changed dramatically with the introduction of molecularly targeted agents such as sunitinib,4–7 pazopanib,8–10 sorafenib,11–14 temsirolimus,15 and everolimus 16. However, according to the resource-stratified guidelines developed at the 2012 Asian Oncology Summit,17 interferon α is still commonly used in Japan and considered the most cost-effective treatment in China 18.…”