First-line chemotherapy with liposomal doxorubicin plus cisplatin for patients with advanced malignant pleural mesothelioma: phase II trial

Abstract

Background:Chemotherapy based on platinum is the standard treatment for unresectable malignant pleural mesothelioma (MPM). Liposomal doxorubicin (LD) consists of pegylated phospholipid vesicles that encapsulate doxorubicin-enhancing liposome deposition in the tumour. We evaluated the toxicity profile and anti-tumour activity of cisplatin plus LD in untreated patients with MPM, as well as 99mTc-LD distribution in MPM lesions after chemotherapy administration.Methods:A total of 38 patients with non-resectable MPM received LD 40 mg m−2 and cisplatin 60 mg m−2 every 21 days. Gamma camera images of 99mTc-LD were acquired to evaluate LD accumulation in measurable tumour tissue. The study was registered in Clinical Trials (NCT00886028).Results:In all, 72% of patients were stage III and 28% were stage IV. Eighty four percent and 16% have high and low risk acording EORTC respectively. The median time to progression was 4.6 months (95% confidence interval (95% CI: 3.4–5.9 months), and median overall survival (OS) was 19.6 months (15.2–37.2 months). Patients that responded to chemotherapy treatment had better survival than patients who did not. Functional physical scales, dysnea, cough, and chest/arm pain demonstrated improvement. The accumulation ratio of LD in tumour and soft tissues vs liver was 0.78±0.16 and 0.29±0.09, respectively. After 1 h of administration, LD uptake in tumour tissue was higher than in soft tissue (P< 0.001).Conclusion:The combination of LD and cisplatin results in an active therapeutic regimen for unresectable MPM, with an acceptable toxicity profile and improvement in quality of life. 99mTc-LD showed higher levels of tumour uptake as compared with surrounding tissues.

Recent progress in development of siRNA delivery vehicles for cancer therapy

“…These facts have encouraged researchers to engineer smaller delivery vehicles with a size of less than 50 nm for enhanced accumulation in heterogeneous tumor tissues. Meanwhile, the EPR effect in human patients has been observed in a handful of examples and is noteworthy [38,39]. A polymer-drug conjugate with a molecular weight of approximately 15 kDa, termed SMANCS, which is able to bind to blood albumin and thereby shows significantly increased blood circulation, was found to accumulate in clinical hepatocellular and renal cell carcinomas with a high vascular density through arterial infusion [40].…”

Rethinking cancer nanotheranostics

“…Accumulation of nanoparticles in primary tumours and, in some cases, in metastases, was observed. Moreover, liposomal doxorubicin plus cisplatin was investigated for treatment against unresectable malignant pleural mesothelioma 18 , and tumour uptake, quantified by 99m Tc-liposome imaging, was positively correlated with patient response and survival 19 . However, in the above studies, the nanotheranostic agents were not assessed for patient stratification, but to evaluate the therapeutic efficacy of the nanomedicines.…”

Tumoral CD10 Expression Correlates with Aggressive Histology and Prognosis in Patients with Malignant Pleural Mesothelioma

“…31 In addition, CD10 has been reported to cleave and activate a peptidic prodrug of doxorubicin, 32,33 and recent clinical trials suggest that chemotherapy with doxorubicin could be effective in patients with malignant pleural mesothelioma, with improvements in quality of life and an acceptable level of toxicity. 34,35 Therefore, CD10 is a potential marker for investigating chemotherapy sensitivity or resistance in patients with malignant pleural mesothelioma.…”