e13507 Background: Malignant pleural mesothelioma (MPM) is a poor prognosis neoplasm. Its worldwide incidence is rising but until recently chemotherapy has not been shown to be effective in its treatment. The combination of cisplatin and pemetrexed is the approved “standard” treatment in unresectable MPM. Liposomal doxorubicin (LD) consists of pegylated phospholipid- vesicles that encapsulate doxorubicin conferring minimal capture from the reticulo-endothelial system resulting in a greater serum half- life, an enhanced liposome deposition in the tumor and a lower degree of toxicity. We evaluated the combination of LD and Cisplatin (Cis) in chemonaive patients with unresectable MPM. Methods: From September 2006 to October 2008, consecutive patients with stage III / IV MPM were included to receive LD 40 mg/m2 and Cis 60 mg/m2 every 21 days for a maximum of 4 cycles. Imaging studies were performed prior and after 2 cycles to assess response. Gamma camera images (GCI) of Tc-99m-labeled LD were acquired to evaluate LD accumulation in measurable tumor tissue. Patients gave written informed consent. Results: Twenty seven patients were included, 81.5% were stage III and 18.5% were IV. According to EORTC prognostic factors, 33.3% and 66.7% had poor and good prognosis, respectively. Median age was 59.2 years (33–80). Median follow-up was of 5.2 ± 0.8 months. Median survival has not been reached. The 2-year overall survival was 52.5% ± 14.2. Median time to progression was 5.0 ± 1.1 months (CI 95%, 2.7–7.3). Overall response was 45.5%, stable disease 36.4% and progression of 18.2%. GCI showed good accumulation and retention (60%) of the labeled LD in tumor tissue at 4 h after the initial injection. There were no toxic deaths. Conclusions: Cis+LD is a highly active regimen in MPM with comparable results to the most active regimens so far reported. A phase III trial is warranted to confirm these findings. No significant financial relationships to disclose.
Tissue distribution and therapeutic effect of intravenous free or encapsulated liposomal doxorubicin on human prostate carcinoma xenografts