Risk of rash and stomatitis with temsirolimus, a mammalian target of rapamycin (mTOR) inhibitor: A meta-analysis.

Abstract

e15031 Background: Temsirolimus, an mTOR inhibitor, is approved for treatment of advanced renal cell carcinoma (RCC). Maculopapular/acneiform rash and stomatitis are the most common mucocutaneous toxicities. We systematically investigated the overall incidence and risk of rash and stomatitis in patients receiving temsirolimus. Methods: Relevant studies were identified from PubMed database (1999-2010) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2010. A citation database Web of Science was searched to ensure that no relevant studies were missed. Eligible studies were limited to prospective Phase II-III clinical trials and expanded-access programs in which cancer patients received temsirolimus 25 mg weekly as a single agent. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. Results: A total of 579 patients from 10 clinical trials were available for analysis. The overall incidence of all-grade and high-grade (grade ≥3) rash was 46.7% (95% CI: 37.5- 56.1) and 3.2% (95% CI: 1.9-5.3), respectively. The overall incidence of all-grade and high-grade stomatitis was 44.3 % (CI: 32.1- 57.1) and 3.2% (95% CI: 1.9-5.4). Temsirolimus was associated with significantly increased risk of all-grade rash and all-grade stomatitis (RR=7.8, 95% CI: 4.5-13.6; P<0.001 and RR=11.1, 95% CI: 5.6-22.0; P<0.001) when compared to patients treated with IFN. The risk of high-grade rash and stomatitis was increased (RR=13.2, 95% CI: 0.8-219.8 and RR=13.2, 95% CI: 0.8-218.5) with a trend reaching statistical significance (P=0.07). No significant difference in incidence of all-grade rash between RCC and non-RCC patients was noted (42.6%, 95% CI: 18.4-70.9% vs. 47.6%, 95% CI: 39.2-56.2%, respectively, p=0.75). Similarly, no difference in all-grade stomatitis was observed (36.5%, 95% CI: 14.9-65.4% and 47.8%, 95% CI: 35.8-60.1%, respectively, p=0.47). Conclusions: Cancer patients treated with temsirolimus are at significant risk for developing skin rash and stomatitis. Further studies for prevention and treatment of these untoward toxicities are needed.