Rapamycin and its analogues (rapalogs) for Tuberous Sclerosis Complex-associated tumors: a systematic review on non-randomized studies using meta-analysis

BACKGROUND: Rapamycin has gained significant attention for its potential activity in reducing the size of TSC-associated tumors, thus providing alternative to surgery. This study aimed at determining the efficacy of rapamycin and rapalogs for reducing the size of TSC-associated solid tumors in patients with Tuberous Sclerosis Complex (TSC). METHODS: Our data sources included electronic searches of the PubMed. We included into our meta-analysis any type of non-randomized study that reported the use of rapamycin and rapalogs for reducing the size of TSC-associated solid tumors in patients with TSC. Data was entered into Cochrane Review Manager Version 5.3 and analyzed. RESULTS: Four case reports and 4 clinical trials were included. Five patients from the case reports (all with SEGA) and 91 patients from the clinical trials (41 with SEGA, 63 with kidney angiomyolipoma and 5 with liver angiomyolipoma) were included into the analysis. Volume and diameter of SEGAs were significantly reduced by mean difference of 1.23 cc (95 % CI −2.32 to −0.13; p = 0.03) and 7.91 mm (95 % CI −11.82 to −4.01; p < 0.0001), respectively. Volume and mean of sum of longest diameter of kidney angiomyolipomas were significantly reduced by mean difference of 39.5 cc (95 % CI −48.85 to −30.15; p <0.00001) and 69.03 mm (95 % CI −158.05 to 12.65; p = 0.008), respectively. In liver angiomyolipomas, however, reduction in tumor size was not evident. Sum of longest diameter of liver angiomyolipomas in 4 patients were enlarged by 2.7 mm (95 % CI 28.42 to −23.02) by the end of treatment, though not significant (p = 0.84). CONCLUSIONS: Rapamycin and rapalogs showed efficacy towards reducing the size of SEGA and kidney angiomyolipoma but not liver angiomyolipomas. This finding is strengthening the conclusion of our Cochrane systematic review on the randomized trials.