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

Andrea Wang-Gillam, Nilay Thakkar, A. Craig Lockhart, Kerry Williams, Maria Baggstrom, Michael Naughton, Rama Suresh, Cynthia Ma, Benjamin Tan, Wooin Lee, Xuntian Jiang, Tibu Mwandoro, Lauren Trull, Stefanie Belanger, Allison N. Creekmore, Feng Gao, Paula M. Fracasso, Joel Picus

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5 Scopus citations


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/m2 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.

Original languageEnglish
Pages (from-to)419-426
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Issue number2
StatePublished - Aug 2014


  • Pegylated liposomal doxorubicin
  • Phase I study
  • Refractory malignancies
  • Temsirolimus


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