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Master Thesis

Impact pronostique de l’exposition pharmacologique aux inhibiteurs de mTOR (mammalian Target of Rapamycin) chez les patients transplantés d’organe solide ayant développé un cancer de novo

Abstract : Backgrounds : metastatic cancers in solid organ transplant patients appear to have a poorer prognosis than in the general population. The study by Rousseau et al, suggests that the introduction of mTOR inhibitor after the diagnosis of metastatic cancer would improve prognosis. The objective of this study is to evaluate the prognostic impact of pharmacological exposure to mTOR inhibitors. Methods : this retrospective study was conducted using the database (2000-2018) of kidney and liver transplant patients at Henri Mondor Hospital in Créteil. All patients who developed solid organ cancer (excluding skin carcinomas) after liver or kidney transplantation and had a conversion to mTOR inhibitors at diagnosis were included. Univariate analyses were performed to determine the role of mTOR inhibitors on overall survival from the diagnosis of metastases. Results : 40 patients were included, with an average age of 55 years, 70% male, including 20 liver transplant patients and 20 kidney transplant patients. Among the 23 patients with metastatic cancer 9 started mTOR inhibitors after the diagnosis of metastases. 24 patients were on sirolimus, with an average dosage of 2.9 +/- 2.1 mg and 13 on Everolimus with an average dosage of 2.2 +/- 1.42 mg. The average duration of treatment with mTOR inhibitors was 33 +/- 28 months. In univariate analysis, overall survival from metastatic diagnosis was 22.4 months for patients on mTOR versus 5.27 months for naïve patients with mTOR, HR = 0.44 (95% CI 0.22-0.88). Overall survival in patients with low residual mTOR concentrations is significantly longer than in naïve mTOR patients with HR = 0.25 (95% CI 0.11-0.57). This difference is not found in patients with high residual concentrations of mTOR versus naïve patients with mTOR, HR = 0.7 (95% CI 0.32-1.54). There is no difference in treatment duration and toxicity between low and high concentrations. Conclusion : the trend towards increased overall survival in metastatic patients with mTOR inhibitors is reported to be more related to a decrease in the intensity of immunosuppression than to the specific anti-tumor effect of mTOR inhibitors.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03129873
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Submitted on : Wednesday, February 3, 2021 - 10:31:19 AM
Last modification on : Wednesday, June 9, 2021 - 3:22:29 AM

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  • HAL Id : dumas-03129873, version 1

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Noémie Claudon. Impact pronostique de l’exposition pharmacologique aux inhibiteurs de mTOR (mammalian Target of Rapamycin) chez les patients transplantés d’organe solide ayant développé un cancer de novo. Médecine humaine et pathologie. 2019. ⟨dumas-03129873⟩

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