Malignant Pleural Mesothelioma Evaluated in a Randomized Study

Malignant Pleural Mesothelioma Evaluated in a Randomized Study

Another interesting study is called, “Randomized trial of doxorubicin versus cyclophosphamide in diffuse malignant pleural Mesothelioma” by Sørensen PG, Bach F, Bork E, Hansen HH – Cancer Treat Rep. 1985 Dec;69(12):1431-2.  Here is an excerpt: “Abstract – The effect of doxorubicin and cyclophosphamide in the treatment of diffuse, malignant pleural mesothelioma was evaluated in a randomized study. All patients were treated on an outpatient basis and none had previously received antineoplastic treatment. All patients had a measurable lesion other than pleural effusion. The treatment consisted of doxorubicin at a dose of 60 mg/m2 every 3 weeks, to a total dose of 550 mg/m2, or cyclophosphamide at a dose of 1500 mg/m2 every 3 weeks for 1 year. At disease progression the treatment was changed to the alternate drug. The dose was increased or decreased according to hematologic effects. Thirty of 32 patients were evaluable for response. Remissions were not achieved in any patient. During treatment with doxorubicin, none of the patients developed cardiotoxicity, while one patient developed hemorrhagic cystitis during treatment with cyclophosphamide. Sepsis or bleeding was not observed in either of the treatment arms. Thus, the trial showed no antineoplastic activity of either doxorubicin or cyclophosphamide in the treatment of malignant pleural mesothelioma.”

Another interesting study is called, “Gene therapy using adenovirus carrying the herpes simplex-thymidine kinase gene to treat in vivo models of human malignant mesothelioma and lung cancer.” By Hwang HC, Smythe WR, Elshami AA, Kucharczuk JC, Amin KM, Williams JP, Litzky LA, Kaiser LR, Albelda SM – Department of Medicine; University of Pennsylvania Medical Center, Philadelphia – Am J Respir Cell Mol Biol. 1995 Jul;13(1):7-16.  Here is an excerpt: “Abstract – Previous studies have shown adenoviral transfer of the herpes simplex virus thymidine kinase (HSVtk) gene followed by the anti-viral drug ganciclovir (GCV) can be used to successfully treat established human mesothelioma tumors growing within the peritoneal cavities of severe combined immune deficient (SCID) mice. These findings raised a number of questions important to the applicability, efficiency, and safety of this treatment strategy. In this report, we have further characterized the use of recombinant adenovirus carrying the HSVtk gene to treat mesothelioma and other localized malignancies. Our results indicate that the Ad.RSVtk/GCV system is effective in causing tumor regression in animals inoculated with another mesothelioma cell line and a lung cancer cell line and that animals with bulky disease can be successfully treated. Effects are seen at a wide range of virus doses and significant anti-tumor activity is present at doses of ganciclovir that are clinically achievable. Finally, this treatment approach appears safe, with limited dissemination of virus using a sensitive RT-PCR detection system. These studies further characterize the use of adenoviral transfer of the HSVtk gene to treat experimental mesothelioma and suggest that clinical trials using this approach may be feasible.

Another interesting study is called, “The diagnostic utility of immunohistochemistry in distinguishing between mesothelioma and renal cell carcinoma: A comparative study
Human pathology” by ORDONEZ Nelson G. – 2004, vol. 35, no6, pp. 697-710 [14 page(s) (article)] (92 ref.)  Here is an excerpt: “Abstract – Both mesotheliomas and renal cell carcinomas can present a wide variety of morphological patterns. Because of this, renal cell carcinomas that metastasize to the pleura and lung may be confused with mesotheliomas. The aim of the present study was to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and renal cell carcinoma. A total of 48 mesotheliomas (40 epithelioid, 8 sarcomatoid), and 48 renal cell carcinomas (24 conventional, 12 chromophobe, 8 papillary, 4 sarcomatoid) were investigated for the expression of the following markers: calretinin, mesothelin, cytokeratin 5/6, WT1, thrombomodulin (TM), N-cadherin, CD15 (leu-M1), MOC-31, Ber-EP4, BG-8 (Lewisy), CD10, renal cell carcinoma marker (RCC Ma), carcinoembryonic antigen (CEA), and B72.3. All (100%) of the epithelioid mesotheliomas reacted for calretinin, mesothelin, and cytokeratin 5/6; 93% for WT1; 78% for TM; 75% for N-cadherin, 48% for CD10, 15% for Ber-EP4,8% for MOC-31, 8% for RCC Ma, 5% for BG-8, and none for CEA, B72.3, or CD15. Of the sarcomatoid mesotheliomas, 88% expressed calretinin, 75% N-cadherin, 38% CD10, and 13% each expressed cytokeratin 5/6, WT1, and TM. All of the remaining markers were negative. Among the RCCs, 81% expressed CD10, 75% N-cadherin, 63% CD15, 50% RCC Ma, 50% MOC-31, 42% Ber-EP4, 8% BG-8, and 2% TM. The remaining markers were negative. The results indicate that calretinin, mesothelin, and cytokeratin 5/6 are the best positive mesothelioma markers for differentiating epithelioid mesotheliomas from renal cell carcinomas. The best discriminators among the antibodies considered negative markers for mesothelioma are CD15, MOC-31, and RCC Ma. An accurate differential diagnosis can be reached with the use of any 2 of the 3 recommended positive markers, which should be selected based on availability and on which ones yield the best staining results in a given laboratory. One of the recommended negative markers may be added to the panel if deemed necessary. If confirmation of renal origin is needed, RCC Ma could be useful. Calretinin is the only marker that appears to have any utility in distinguishing between sarcomatoid mesotheliomas and sarcomatoid renal cell carcinomas.”

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

Monty Wrobleski is the author of this article.  For more information please click on the following links

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