Publications [#168948] of Mark W. Dewhirst

Papers Published

1. A Alvarez Secord, EL Jones, CA Hahn, WP Petros, D Yu, LJ Havrilesky, JT Soper, A Berchuck, I Spasojevic, DL Clarke-Pearson, LR Prosnitz, MW Dewhirst, Phase I/II trial of intravenous Doxil and whole abdomen hyperthermia in patients with refractory ovarian cancer., International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, England, vol. 21 no. 4 (June, 2005), pp. 333-47, ISSN 0265-6736
   (last updated on 2009/12/31)

   Abstract:
   OBJECTIVE: A phase I/II study of Doxil combined with whole abdomen hyperthermia was conducted in patients with refractory ovarian cancer. Liposomal doxorubicin combined with hyperthermia has been shown to increase both liposomal delivery and drug extravasation into tumour xenografts resulting in enhanced cytotoxic effects. PATIENTS AND METHODS: Thirty patients with either recurrent or persistent epithelial ovarian cancer were enrolled. All patients had either measurable or assessable disease. Patients received intravenous (IV) Doxil at a dose of 40 mg m-2 as a 1-h infusion followed by whole abdomen hyperthermia. The phase I portion of the study was performed to determine the maximal tolerated dose (MTD) of hyperthermia. Quality of life (QoL) was performed at baseline, prior to each cycle and every 3 months. Plasma pharmacokinetic studies were performed with the first cycle. RESULTS: Ten patients participated in the phase I portion of the study which demonstrated that the MTD of hyperthermia was 60 min after either average vaginal and rectal temperatures of 40 degrees C had been achieved or after 30 min of power application, whichever was shorter. All 30 patients were either paclitaxel and/or platinum resistant initially or developed resistant disease. The median number of prior chemotherapeutic regimens was three (range 2-8) and six patients had been previously treated with Doxil. There were three partial responses for a response rate of 10% (95% CI: [2%, 27%]) and eight patients (27%; 95% CI: [12%, 46%]) had disease stabilization. The median time to progression or death was 3.4 months (95% CI: [2.6, 5.2]) and the median survival was 10.8 months (95% CI: [8.8, 17.4]). Twelve patients (40%) experienced palmar-plantar erythrodysesthesia (PPE), but only four (13%) experienced grade 3-4 PPE toxicity. Doxil systemic exposure was higher in those with grade 3-4 PPE compared to those with no PPE. None of the patients had grade 3-4 thermal toxicity due to hyperthermia. QoL was not decreased in patients responding to therapy. CONCLUSIONS: Therapy with intravenous Doxil and whole abdomen hyperthermia for patients with platinum/paclitaxel resistant ovarian cancer is feasible and does not negatively impact quality of life.

   Keywords:
   Aged • Antineoplastic Agents • Combined Modality Therapy • Doxorubicin • Female • Humans • Hyperthermia, Induced* • Middle Aged • Ovarian Neoplasms • Quality of Life • adverse effects • drug therapy • pharmacokinetics • therapeutic use* • therapy*