Mesothelioma and Continuous Infusion Paclitaxel Administered with Large Field Irradiation

Another interesting study is called, "Phase I study of paclitaxel as a radiation sensitizer in the treatment of mesothelioma and non-small-cell lung cancer" by LL Herscher, SM Hahn, G Kroog, H Pass, B Temeck, B Goldspiel, J Cook, JB Mitchell and J Liebmann
Radiation Oncology Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892 - Journal of Clinical Oncology, Vol 16, 635-641.  Here is an excerpt: "PURPOSE: To determine the maximum-tolerated dose (MTD) and dose- limiting toxicities of paclitaxel with concurrent thoracic irradiation in patients with malignant pleural mesothelioma and locally advanced non-small-cell lung cancer (NSCLC) using a 120-hour continuous infusion regimen. A secondary objective was to assess the effect of paclitaxel on the cell cycle through serial tumor biopsies. PATIENTS AND METHODS: Paclitaxel was administered as a 120-hour (5-day) continuous infusion repeated every 3 weeks during the course of radiation therapy. The starting dose of paclitaxel was 90 mg/m2. Doses were escalated at 15- mg/m2 increments in successive cohorts of three patients. In NSCLC patients, radiation was delivered to the primary tumor and regional lymph nodes for a total tumor dose of 6,120 cGy. In mesothelioma patients, hemithoracic irradiation was delivered as the initial treatment field with a conedown to the tumor volume for a total dose of 5,760 to 6,300 cGy. Tumor biopsies were obtained, if possible, before and during paclitaxel treatment. RESULTS: Thirty patients were entered onto this study through three dose levels (from 90 mg/m2 to 120 mg/m2). The MTD was determined to be 105 mg/m2. The dose-limiting toxicity was grade 4 neutropenia (two patients). Grade 2 gastrointestinal (GI) toxicity (nausea and vomiting) was also observed at 120 mg/m2. Three of 30 patients developed a hypersensitivity reaction. Six patients had grade 2 lung injury manifested by a persistent cough that required antitussives. Five patients underwent tumor biopsies. None of the patients showed a significant block of cells in mitosis (G2/M) after paclitaxel infusion. CONCLUSION: The MTD of paclitaxel, when administered as a 120-hour continuous infusion with concurrent radiotherapy, was determined to be 105 mg/m2. The dose-limiting toxicity was neutropenia. Continuous infusion paclitaxel administered with large field irradiation of the lung is well tolerated and deserves continued evaluation."

Another interesting study is called, "Photodynamic therapy for human malignant mesothelioma in the nude mouse" - Journal of Surgical Research Volume 49, Issue 4, October 1990, Pages 311-314 by Richard H. Feins M.D., Russell Hilf Ph.D, Howard Ross B.S. and Scott L. Gibson B.S.  Here is an excerpt: "Abstract - Photodynamic therapy (PDT) utilizes a photoactivatable preparation, Photofrin II, which selectively localizes in cancerous tissue and produces substances toxic to that tissue when activated by light. Whether PDT would be able to selectively destroy human malignant mesothelioma was investigated by using a human-derived malignant mesothelioma tumor subcutaneously implanted in nude mice. Human malignant mesothelioma was grown subcutaneously to a size of 0.2 – 0.4 cm3. Selective retention of Photofrin II was studied by measuring light-induced inhibition of cytochrome c oxidase activity in tumor, heart, and lung. Photofrin II was retained in greater quantities in tumor than in heart or lung at 24 hr after injection. Using laser light at 630 nm under varying conditions, tumor growth was measured every 2 days following PDT for 18 days. All PDT regimens were successful in destroying malignant mesothelioma. Photofrin II at 5 mg/kg was superior to 2 mg/kg (P < 0.005), light delivered at 50 mW/cm2 × 2 hr was superior to that delivered at 200 mW/cm2 × 30 min (P < 0.05), and a total fluence of 180 J/cm2 was equivalent to 360 J/cm2 in affecting tumor growth. Ten of 12 mice treated at 50 mW/cm2 became tumor-free and remained so for 30 days following treatment. We concluded that PDT was effective against human malignant mesothelioma in a nude mouse model without adversely affecting the animal. A role for PDT in treating patients with malignant mesothelioma may exist."

Another interesting study is called, "Diagnostic significance of carcinoembryonic antigen in the differential diagnosis of malignant Mesothelioma" by J Mezger, R Lamerz and W Permanetter - Department of Internal Medicine III, Klinikum Grosshadern, Munich, Federal Republic of Germany. The Journal of Thoracic and Cardiovascular Surgery, Vol 100, 860-866.  Here is an excerpt; "The histologic and cytologic distinction of malignant mesothelioma from carcinomas metastatic to the pleura or peritoneum is often problematic. For this reason immunologic methods are being increasingly used as diagnostic adjuncts. This review summarizes 40 studies on the expression of carcinoembryonic antigen in mesotheliomas and in lung and other carcinomas involving the pleura or peritoneum. Carcinoembryonic antigen was identified immunohistochemically in 11% of mesotheliomas and in 84% of carcinomas examined and immunocytochemically (in serous effusions) in 4% and 58%, respectively. In serum and in pleural or ascitic fluid, significantly elevated levels of carcinoembryonic antigen are commonly associated with (lung) carcinomas but rarely with mesotheliomas. Thus, together with identification of the antigen in serum, pleural fluid, or ascitic fluid, immunohistochemical and immunocytochemical techniques for detecting carcinoembryonic antigen provide a valuable aid for distinguishing malignant mesothelioma from metastatic 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.