1.
m-TOR inhibitors and risk of Pneumocystis pneumonia after solid organ transplantation: a systematic review and meta-analysis.
Ghadimi, M, Mohammadpour, Z, Dashti-Khavidaki, S, Milajerdi, A
European journal of clinical pharmacology. 2019;(11):1471-1480
Abstract
PURPOSE Although there is controversy, some evidences proposed increased risk of post-transplant Pneumocystis carinii pneumonia (PCP) in patients receiving mammalian target of rapamycin (mTOR) inhibitors. This study aimed to examine the association between m-TOR inhibitors and the risk of developing PCP in solid organ transplant (SOT) recipients. METHODS A comprehensive search was performed to find the eligible studies that investigated the incidence of PCP in patients treated with mTOR inhibitors after SOT. Random effect model was applied for meta-analysis. RESULTS Combination of 15 effect sizes showed a significant positive association between mTOR inhibitor administration and the risk of PCP (OR = 1.90, 95%CIs = 1.44, 2.75). There was no heterogeneity between studies (I2 = 3.5%). Subgroup analysis revealed increased risk of PCP after the first year of transplantation (P < 0.001). CONCLUSION In conclusion, administration of mTOR inhibitors is a potential risk factor for late-onset PCP after SOT. Targeted PCP prophylaxis based on recipients' risk factors rather universal prophylaxis may lessen the risk.
2.
Fatigue with vascular endothelial growth factor receptor tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors in patients with renal cell carcinoma (RCC) and other malignancies: A meta-analysis of randomized clinical trials.
Ghatalia, P, Je, Y, Nguyen, PL, Trinh, QD, Choueiri, TK, Sonpavde, G
Critical reviews in oncology/hematology. 2015;(2):251-63
Abstract
A trial-level meta-analysis of randomized phase II/III controlled trials in renal cell carcinoma (RCC) and other malignancies was conducted to systematically determine the relative risk (RR) of fatigue, a common side effect associated with single agent therapy with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) and mammalian target of rapamycin inhibitors (mTORi). The RR of all grade fatigue and high grade fatigue in 7304 patients from 19 trials was 1.35 (95% CI 1.22-1.49, p<0.001) and 1.33 (95% CI 0.97-1.82, p=0.08), respectively in patients receiving VEGFR TKIs or mTORi. The summary incidence of all grade and high grade fatigue in the drug arm was 38.2% (95% CI 31.8-45.1) and 4.0% (95% CI 2.8-5.7), respectively. The type of drug (VEGFR TKI vs. mTORi), line of therapy, age, type of tumor (RCC vs. others) and median duration of therapy did not affect the risk of all-grade fatigue.