Phase II trial of liposomal daunorubicin in malignant pleural mesothelioma

This review summarises the results of previously conducted clinical trials, and subsequently presents data arising from all phase II -III studies on chemotherapy of malignant pleural mesothelioma (MPM) published since the last relevant overview. While response rates exceeding 30% have barely been achieved with established cytotoxic drugs in MPM therapy, novel chemotherapeutic agents and their combinations appear more promising. This applies especially to the antimetabolites, and in particular to pemetrexed that produced response rates of up to 45% in combination with platinum compounds. Raltitrexed combined with oxaliplatin has also been shown to be effective, and gemcitabine -applied as a single agent or in combination with cisplatin -as well as vinorelbine appear to improve the quality of life in patients presenting with MPM. Data can now be more precisely analysed by increasingly implemented randomised studies, applying a standardised staging system, and distinguishing prognostic groups. While chemotherapy for MPM remains a challenging task, important steps have clearly been made in the past years to combat this aggressive disease. The publication of pemetrexed with cisplatin phase III results in a peer-reviewed journal may soon establish a standard of care.

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“…Liposomal daunorubicin (LD) was given to 13 patients at 120 mg m À2 every 3 weeks, but no responses were produced (Steele et al, 2001).…”

Section: Liposomal Anthracyclinesmentioning

confidence: 99%

Chemotherapy for malignant pleural mesothelioma: past results and recent developments

Tomek

Manegold

2004

Lung Cancer

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“…Multiple single agent and combination chemotherapy regimens have been evaluated [10; 11]. No clearly effective therapy emerged until recently, with response rates ranging from 11 to 20% [12; 13; 14], but overall survival remaining less than 12 months. In reviewing the data, there is a suggestion that antimetabolite drugs have better efficacy than other cytotoxic agents [15].…”

Section: Introductionmentioning

confidence: 99%

An epigenetic mechanism for capecitabine resistance in mesothelioma

Kosuri

Wang

et al. 2010

Biochemical and Biophysical Research Communications

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Mesothelioma is an uncommon malignancy whose global incidence continues to rise. The therapeutic standard for advanced disease is intravenous pemetrexed and cisplatin. The antifolate capecitabine is significantly less effective than pemetrexed. The balance between thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and Thymidine Phosphorylase (TP) is critical to the efficacy of capecitabine. DNA from mesothelioma cell lines was bisulfite treated and examined by MS-PCR, RNA was obtained for real time PCR analysis, and protein lysates were obtained for Western immunoblot analysis. Cytotoxicity was assessed by MTT assay, comparing 5-aza-CdR pretreated or untreated cells with 5′-Deoxy-5-fluorouridine (DFUR), 5-FU, and pemetrexed. Finally bisulfite sequencing of the extracellular growth factor-1 (ECGF-1) gene was performed on 4 mesothelioma samples and pericardial tissue. One of the four cell lines tested (H290) was methylated for ECGF-1. This corresponded to a lack of TP expression by real time PCR and Western immunoblot. Treatment with 1 μM 5-aza-CdR increased TP mRNA and protein expression in H290. DFUR, the substrate for TP, showed increased cytotoxicity when delivered after 5-aza-CdR exposure in the methylated cell line. There was no difference in any of the unmethylated cell lines when cells were exposed to 5-FU or pemetrexed with or without 5-aza-CdR. Patient tumor samples revealed an increased number of methylated CpG sites in ECGF-1 compared to normal pericardium. Methylation of ECGF-1, leads to transcriptional silencing of TP and may explain the lack of any effect of capecitabine, especially when compared to pemetrexed.

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“…27 Hypersensitivity reactions to liposomal formulations are very uncommon, but hemodynamic, respiratory, cutaneous and subjective manifestations include hypotension or hypertension, dyspnea, flushing, rash, and a feeling of choking has been seen in up to 30.8% of the patients. [28][29][30][31] These hypersensitivity reactions are easily controlled by slowing of the rate, or stopping the infusion, and standard measures of anaphylaxis prevention and treatment also usually seem to be sufficiently effective.…”

Section: Liposomesmentioning

confidence: 99%

Impact of nanotechnology in cancer: emphasis on nanochemoprevention

Mukhtar¹

2012

IJN

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Since its advent in the field of cancer, nanotechnology has provided researchers with expertise to explore new avenues for diagnosis, prevention, and treatment of the disease. Utilization of nanotechnology has enabled the development of devices in nanometer (nm) sizes which could be designed to encapsulate useful agents that have shown excellent results but otherwise are generally toxic due to the doses intended for extended use. In addition, examples are also available where these devices are easily conjugated with several purposeful moieties for better localization and targeted delivery. We introduced a novel concept in which nanotechnology was utilized for enhancing the outcome of chemoprevention. This idea, which we termed as "nanochemoprevention," was subsequently exploited by several laboratories worldwide and has now become an advancing field in chemoprevention research. This review examines some of the up and coming applications of nanotechnology for cancer detection, imaging, treatment, and prevention. Further, we detail the current and future utilization of nanochemoprevention for prevention and treatment of cancer.

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Phase II trial of liposomal daunorubicin in malignant pleural mesothelioma

Cited by 35 publications

References 7 publications

Chemotherapy for malignant pleural mesothelioma: past results and recent developments

Chemotherapy for malignant pleural mesothelioma: past results and recent developments

An epigenetic mechanism for capecitabine resistance in mesothelioma

Impact of nanotechnology in cancer: emphasis on nanochemoprevention

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