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A phase I study of pegylated liposomal doxorubicin and temsirolimus in patients with refractory solid malignancies

This study aimed to determine the maximum-tolerated dose and dose-limiting toxicities of pegylated liposomal doxorubicin (PLD) in combination with temsirolimus (T) in patients with refractory solid tumors. Using a standard “3+3” dose escalation design, 23 patients were enrolled in three dosing cohor...

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Detalles Bibliográficos
Autores principales: Wang-Gillam, Andrea, Thakkar, Nilay, Lockhart, A. Craig, Williams, Kerry, Baggstrom, Maria, Naughton, Michael, Suresh, Rama, Ma, Cynthia, Tan, Benjamin, Lee, Wooin, Jiang, Xuntian, Mwandoro, Tibu, Trull, Lauren, Belanger, Stefanie, Creekmore, Allison N., Gao, Feng, Fracasso, Paula M., Picus, Joel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112045/
https://www.ncbi.nlm.nih.gov/pubmed/24916546
http://dx.doi.org/10.1007/s00280-014-2493-x
Descripción
Sumario:This study aimed to determine the maximum-tolerated dose and dose-limiting toxicities of pegylated liposomal doxorubicin (PLD) in combination with temsirolimus (T) in patients with refractory solid tumors. Using a standard “3+3” dose escalation design, 23 patients were enrolled in three dosing cohorts in this phase I study. The starting dose level was PLD at 30 mg/m(2) every 4 weeks and T at 20 mg weekly. Pharmacokinetics (PK) of doxorubicin were evaluated for patients in the expansion cohort. The most common treatment-related adverse events of all grades were mucositis/stomatitis (69.6 %), anorexia (52.2 %), thrombocytopenia (52.2 %), and fatigue (47.8 %). The recommended doses of this combination for phase II studies are 25 mg/m(2) PLD and 25 mg T. PK analyses suggested increased exposure of doxorubicin in this combination regimen compared to doxorubicin administered as a single agent, possibly due to PK drug interactions. Out of 18 patients evaluable for a treatment response, two had partial responses (PR) (breast cancer and hepatocellular carcinoma) and six had stable disease (SD). Two patients remained on treatment for more than 1 year. The combination of PLD and T is tolerable, and the treatment resulted in clinical benefit. The combination regimen should be further explored in appropriate tumor types. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00280-014-2493-x) contains supplementary material, which is available to authorized users.