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
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