Demonstrating The Feasibility Of Intrapleural Cisplatin-based Chemotherapy

One interesting study is called, “Trials in malignant mesothelioma. LCSG 851 and 882. Rusch VW” - Chest. 1994 December 106 (6 Suppl) : 359S-362S - Thoracic Surgery Service, Memorial Sloan-Kettering Cancer Center, New York 10021. Here is an excerpt: “Abstract - In 1985 the Lung Cancer Study Group (LCSG) initiated clinical trials in malignant pleural mesothelioma because LCSG member institutions had access to large numbers of patients and had significant experience treating this uncommon cancer. The first trial, LCSG 851, defined the patient population seen by the LCSG, and the feasibility of performing surgical resection by extrapleural pneumonectomy in a multi-institutional setting. Of 83 patients entered on this study from September 1985 to June 1988, only 20 could undergo an extrapleural pneumonectomy, and 3 of 20 patients died postoperatively. This experience prompted the LCSG to explore combining a potentially less morbid operation, pleurectomy/decortication, with adjuvant therapy. The results of another LCSG trial (LCSG 861) and of a small single institutional pilot study demonstrated the feasibility of intrapleural cisplatin-based chemotherapy, and led to the development of LCSG 882, which combined pleurectomy/decortication with postoperative intrapleural, and subsequent systemic, cisplatin-based chemotherapy. This study was not completed because of discontinuation of funding for the LCSG. However, a single-institution phase 2 trial of very similar design has subsequently shown the feasibility of this combined modality approach.”

Another study is called, “Extended Surgical Staging for Potentially Resectable Malignant Pleural Mesothelioma” by David C. Rice, MB, BCh, Jeremy J. Erasmus, MD, Craig W. Stevens, MD, PhD, Ara A. Vaporciyan, MD, Judy S. Wu, BS, Anne S. Tsao, MD, Garrett L. Walsh, MD, Stephen G. Swisher, MD, Wayne L. Hofstetter, MD, Nelson G. Ordonez, MD, W. Roy Smythe, MD - Ann Thorac Surg 2005;80:1988-1993 - Department of Thoracic and Cardiovascular Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Here is an excerpt: “BACKGROUND: Extrapleural pneumonectomy for malignant pleural mesothelioma (MPM) is a high-risk procedure, and patients require careful preoperative staging to exclude advanced disease. Computed tomography, magnetic resonance imaging, and positron emission tomography are useful staging modalities, but do not reliably identify contralateral mediastinal involvement or transdiaphragmatic invasion. We evaluated the role of extended surgical staging procedures, which generally includes a combination of laparoscopy, peritoneal lavage, and mediastinoscopy, to more precisely stage patients with MPM.

METHODS: One hundred eighteen patients with MPM, deemed clinically and radiologically resectable, underwent extended surgical staging. Mediastinoscopy was performed in 111 patients, laparoscopy in 109 patients, and peritoneal lavage in 78 patients.

RESULTS: Ten (9.2%) patients had gross evidence of transdiaphragmatic or peritoneal involvement. Peritoneal lavage was positive for metastatic MPM in 2 (2.6%) patients, neither of whom had obvious transdiaphragmatic invasion. Ipsilateral mediastinal nodes contained metastatic tumor in 10 of 62 (16.1%) patients. Contralateral nodes were positive in 4 of 111 (3.6%) patients. Of the patients who underwent biopsy of both ipsilateral and contralateral mediastinal nodes, and who had complete pathologic staging after extrapleural pneumonectomy (n = 46), 14 (30.4%) had N2-positive nodes. Only 5 of these patients were correctly identified by mediastinoscopy (sensitivity 36%, accuracy 80%). Extended surgical staging identified 16 (13.6%) patients who had contralateral nodal involvement, transdiaphragmatic invasion, or positive peritoneal cytology.

CONCLUSIONS: Extended surgical staging defines an important subset of patients with unresectable MPM not identified by imaging. Because of the potential morbidity associated with extrapleural pneumonectomy, we advocate that extended surgical staging be performed in all patients with MPM before resection.

Another interesting study is called, “Phase II study of a short course of weekly high-dose cisplatin combined with long-term oral etoposide in pleural Mesothelioma” - Oxford Journals Medicine Annals of Oncology Volume 6, Issue 6 Pp. 613-616 - A. S. T. Planting1, M. E. L. van der Burg, S. H. Goey, J. H. M. ScheUens, M. J. van den Bent, M. de Boer-Dennert, G. Stoter1 and J. Verweij. Here is an excerpt: “Abstract - Background In a previous phase II study with a dose-intensive weekly cisplatin schedule for six cycles, we observed a partial response in 5 of 14 patients with pleural mesothelioma. However, response duration was short (median 6 months). Since oral etoposide may theoretically be synergis-tic to cisplatin, we performed a phase II study with the combination of both drugs. Patients and methods Twenty-five chemo-naive patients with pleural mesothelioma were treated with cisplatin 70 mg/m2 days 1–8–15 and days 29–36–43 in combination with oral etoposide 50 mg days 1–15 and days 29–43. Patients with stable disease, or better, continued treatment with oral etoposide 50 mg/m2/day days 1–21 every 28 days. Results All patients were evaluable for response and toxicity. Complete response was observed in one patient and partial responses in 5 patients (RR% 24%; 95% Cl: 10%–45%) for a median duration of 30 weeks. Twelve patients had stable disease. The response status never improved during maintenance treatment with oral etoposide. Most patients tolerated the regimen very well. Toxicity was mainly haema-tologic with leukocytopenia causing treatment delays in 8 patients. Ototoxicity grade 1 or 2 was observed in 8 patients, neurotoxicity grade 1 in 9 patients and nephrotoxicity grade 1 in 1 patient. Conclusion Frequently administered cisplatin in combination with oral etoposide has a moderate but definite activity in pleural mesothelioma

By: montee wrobleskee

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