Gemcitabine and Malignant Mesothelioma


AFIRI, D.M. THOMAS, N.A. SHEPHERD, T. KRAUSZ, D.P. LANE, P.A. HALL – Histopathology – Volume 21, Issue 4, pages 331–334, October 1992.  Here is an excerpt: “The p53 tumour suppressor gene has been shown to be frequently mutated in a wide range of human neoplasms. This is accompanied by increased levels of p53 protein which become immunologically detectable in pathological material. We have investigated the possibility that the differential diagnosis between reactive and neoplastic mesothelium might be resolved using a polyclonal serum raised to human p53 protein, CM-1. None of 20 cases of reactive mesothelial proliferation showed p53 immunoreactivity while 70% (14 of 20) of cases of malignant mesothelioma showed p53 staining. We can thus infer that abnormalities of p53 appear to be a common event in malignant mesothelioma and that p53 immunostaining may be of value in the distinction of malignant mesothelioma from reactive hyperplasia.”

Another interesting study is called, “Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural Mesothelioma” by
W Weder, RA Stahel,, J Bernhard, S Bodis, P Vogt, P Ballabeni, D Lardinois, D Betticher, R Schmid, R Stupp, HB Ris, M Jermann, W Mingrone, AD Roth and A Spiliopoulos – Here is an excerpt: “Abstract – Background: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome. Patients and methods: Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1–T3, N0–2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients.  Results: In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6–24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6–32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5).  Conclusions: The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distress.”

Another interesting study is called, “The role of gemcitabine in the treatment of malignant Mesothelioma” by Hedy Lee Kindler, Jan.P. van Meerbeeck – Volume 29, Issue 1, Pages 70-76 (February 2002).  Here is an excerpt: “ABSTRACT – Gemcitabine is broadly active in a variety of solid tumors, including malignant mesothelioma. In vitro, gemcitabine demonstrates activity against mesothelioma cell lines. The role of single-agent gemcitabine in patients with mesothelioma is unclear, since three phase II trials treated a total of 60 patients and achieved response rates of 0%, 7%, and 31%. The combination of gemcitabine and cisplatin is synergistic against mesothelioma cell lines in vitro. Gemcitabine in combination with cisplatin or carboplatin shows definite activity in phase II trials. The trial by Byrne and colleagues that demonstrated a response rate of 48% established the combination of gemcitabine plus cisplatin as a standard therapy for this disease in the United States. Subsequent multicenter trials have achieved lower response rates of 26% and 16% for this combination. Gemcitabine plus carboplatin also has activity. Future roles for gemcitabine in malignant mesothelioma patients include incorporating a gemcitabine/platinum regimen for neoadjuvant or adjuvant therapy, combining it with other cytotoxic chemotherapy agents such as pemetrexed or vinorelbine, or adding novel cytostatic agents such as the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, to the gemcitabine and platinating agent combination.” Semin Oncol 29:70-76

We all owe a debt of gratitude to these fine researchers for their work.  If you found any of these excerpts helpful, please read the studies in their entirety.

 

From Dallas – According to a report published in the Journal of the American Medical Association, lung cancer survival rates may improve with precision radiation therapy. Researchers studied over 50 lung cancer patients who were unable to undergo surgery to remove their tumors. They found that lung cancer did not recur in nearly 98% of participants who underwent precision radiation therapy, and that 56% still lived three years following their diagnosis. From the UK – Antidepressants appear to help patients suffering from physical illnesses, according to a report published in the Cochrane Library. Researchers reviewed 51 studies covering over 3600 patients with physical illnesses such as stroke, HIV/AIDS and cancer. They found that antidepressants proved more effective than placebos at treating depression in these patients. And finally, from Atlanta – According to a report presented at the American College of Cardiology meeting, heart patients who received a stent may find their survival improve with cardiac rehabilitation. Researchers studied over 2300 patients who underwent stent placement, finding up to 47% decrease in mortality among those who participated in cardiac rehabilitation.

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