Cancer Treatment Today » Mesothelioma

First line chemotherapy for mesothelioma – pro

M Levin, MD — Tue, 25 Sep 2012 17:40:06 +0000

For first line unresectable pleural mesothelioma, NCCN recommends: Alimta and carboplatin or cisplatin every 3 weeks as a Category 1 recommendation. In various studies, these combinations obtained overall response rate of 26.3% in 745 mesothelioma patients, and the combination of pemetrexed and carboplatin was associated with an overall response rate of 21.6%. One-year survival rate was 63 to 64%. The researchers’ findings were derived from an analysis of outcome data on 1,704 chemotherapy-naive patients.

NCCN also advises gemcitabine/cisplatin or Alimta or vinorelbine as a single agent . It also now recommends pemetrexed/cisplatin/bevacizumab followed by maintenance bevacizumab as a first‐line treatment option for patients with unresectable malignant pleural mesothelioma. This is a category 2A recommendation.

In a Phase III randomized, open-label trial, Avastin in combination with pemetrexed and cisplatin (CP) followed by Avastin maintenance significantly improved the primary outcome measure of median overall survival by 2.75 months from 16.07 to 18.82 months (stratified HR=0.76, 95%CI [0.61-0.94], p=0.0127) vs. CP alone in chemotherapy-naive malignant pleural mesothelioma patients. Progression-free survival was also significantly improved in the Avastin arm by 2 months from 7.48 to 9.59 months (stratified HR=0.61; 95%CI [0.50-0.75].
Substituting carboplatin is supported by peer-reviewed medical literature: Santoro et al and Razak et al.

Zalcman G, Mazières J, Margery J, et al. Bevacizumab 15mg/kg plus cisplatinpemetrexed (CP) triplet versus CP doublet in Malignant Pleural Mesothelioma (MPM): Results of the IFCTGFPC0701 MAPS randomized phase 3 trial [abstract]. J Clin Oncol 2015; 33:Abstract 7500.

Santoro A1, O’Brien ME, Stahel RA, Nackaerts K, Baas P, Karthaus M, Eberhardt W, Paz-Ares L, Sundstrom S, Liu Y, Ripoche V, Blatter J, Visseren-Grul CM, Manegold C. Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaïve patients with malignant pleural mesothelioma: results of the International Expanded Access Program.J Thorac Oncol. 2008 Jul;3(7):756-63.

Kindler HL, Karrison TG, Gandara DR, et al. Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma. J Clin Oncol 2012;30:2509-2515.

Ceresoli GL, Zucali PA, Mencobono M, et al. Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma. Br J Cancer. 2013 Aug 6;109(3):552-8. doi: 10.1038/bjc.2013/bjc.2013.368. Epub 2013 Jul 16. 3. Dowell JE, Dunphy FR, Taub RN, et al. A multicenter, phase II study of cisplatin, pemetrexed and bevacizumab in patients with advanced malignant mesothelioma. Lung Cancer. 2012 Sep;77(3):567-71.

doi:10.1016/j.lungcan.2012.05.111. Epub 2012 Jul 4. 4. Jackman DM, Kindler HL, Yeap BY, et al. Erlotinib plus bevacizumab in previously treated patients with malignant pleural mesothelioma. Cancer. 2008 Aug 15;113(4):808-14: 10.1002/cncr.23617

NCCN, MPM-B, 1 2016

Santoro A, O’Brien ME, Stahel RA, Nackaerts K, Baas P, Karthaus M, Eberhardt W, Paz-Ares L, Sundstrom S, Liu Y, Ripoche V, Blatter J, Visseren-Grul CM, Manegold C. Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaïve patients with malignant pleural mesothelioma: results of the International Expanded Access Program. J Thorac Oncol. 2008 Jul;3(7):756-63.

Li L, Razak AR, Hughes A. Carboplatin and pemetrexed in the management of malignant pleural mesothelioma: A realistic treatment option? Lung Cancer. 2008 Oct 14.

For Lay version see here

Chemotherapy for mesothelioma gemcitabine and oxaliplatin – pro

admin — Sat, 01 Sep 2012 19:56:52 +0000

Lay Summary: Gemcitabine and oxaliplatin combination is promising but needs more study for mesothelioma.

Most patients with malignant mesothelioma are candidates for systemic chemotherapy during the course of their disease, but no standard regimen has been established. Several phase II single-agent and combination chemotherapy studies have been performed over the past two decades. There are tow studies of the gemcitabine/ oxaliplatin combination to my knowledge, a retropsective revieew and two phase II studies, with small numbers of patients. Although the true impact of chemotherapy in mesothelioma remains to be determined, agents with consistent antitumor activity include the platinum agents and the antifolates. Recent data from a large randomized phase III clinical trial established the superiority of cisplatin/pemetrexed compared to cisplatin alone.

Pasi A. Jänne First-Line Chemotherapy for Malignant Pleural Mesothelioma in
Malignant Mesothelioma
Advances in Pathogenesis, Diagnosis, and Translational Therapies , 2006
ed. Harvey I. Pass, Nicholas J. Vogelzang and Michele Carbone

M. S. Boyar, M. Hesdorffer, R. N. Taub Phase II trial of oxaliplatin and gemcitabine in patients with malignant pleural or peritoneal mesotheliomaJournal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 17133

Intrapleural chemotherapy – pro

admin — Sat, 01 Sep 2012 19:55:03 +0000

Intrapleural chemotherapy is given through large or small chest catheters that may be connected to an implantable port. These catheters can be used to give drugs as well as to drain fluid that often accumulates in the pleural or peritoneal cavity when cancer has spread to these areas. Malignant pleural effusion (MPE) is a common and life-threatening problem in patients with advanced malignancies. In most cases, MPE is controlled by tube drainage combined with pleurodesis and the intrapleural instillation of various sclerosing or chemotherapeutic agents. Most reports on intrapleural chemotherapy are dated and consist of case reports and case series. There are no propective studies and it is not known how it performs aganst pleurodysis or systemic chemotherapy alone.

Erasmus, Jeremy J. MD; Patz, Edward F. Jr MD Treatment of malignant pleural effusions. Current Opinion in Pulmonary Medicine. 5(4):250, July 1999.

Tan, A. Sedrakyan, J. Browne, S. Swift, and T. Treasure
The evidence on the effectiveness of management for malignant pleural effusion: a systematic review.
Eur. J. Cardiothorac. Surg., May 1, 2006; 29(5): 829 – 838.

Alimta and cisplatin for mesothelioma – pro

admin — Sat, 01 Sep 2012 19:53:56 +0000

Anticancer responses were achieved in 32.5% of patients treated with Alimta/cisplatin compared with 5.5% for patients treated with Alimta alone.
Anticancer responses plus disease stabilization (disease control rate) was achieved in nearly 69% of patients treated with Alimta/cisplatin, and 47% for those treated with Alimta alone.
Half of the patients were alive at 7.6 months among those treated with Alimta/cisplatin, compared with 4.1 months for those treated with Alimta alone.
Serious side effects were generally rare, with dehydration and nausea being the most common.
The researchers concluded that treatment with Alimta/cisplatin or Alimta alone produces anticancer benefits among patients with recurrent mesothelioma. The combination of Alimta/cisplatin appeared to provide greater activity than Alimta alone; however, both treatment options may be considered for this challenging disease. The combined regimen and Alimta alone are FDA approved for mesothelioma.

Janne P, Wozniak A, Belani C, et al. Pemetrexed Alone or in Combination with Cisplatin in Previously Treated Malignant Pleural Mesothelioma: Outcomes from a Phase IIIB Expanded Access Program. Journal of Thoracic Oncology. 2006; 1: 506-512.

Chemotherapy and Avastin for mesothelioma – pro

admin — Sat, 01 Sep 2012 19:48:18 +0000

Avastin has been tesed in phase II in mesothelioma, usually in combinaiton. Results are not always positive. For example, a 2009 abstract concluded that adding Avsatin to Alimta and cisplatin does not improve PFS when compared with historical controls of PC in advanced MM pts.
The NCCN Guidelines recommends pemetrexed (Alimta®, Lilly USA, LLC) with cisplatin (Platinol®, Bristol-Myers Squibb) or carboplatin (Paraplatin®, Bristol-Myers Squibb), or gemcitabinecisplatin, premetrexed or vinorelbine as the optimal first-line chemotherapy regimen for patients. A few specific drugs are listed as second line options in the NCCN Guidelines: premeterexed, if not previously used, vinorelbine or gemcitabine.
J. Dowel, R. Taub, C. Lan, Y. Xie, F. Dunphy, V. Blake, H. Kindler; UT Southwestern, Dallas, TX; Columbia University, New York, NY; Duke University, Durham, NC; University of Chicago, Chicago, IL
A multicenter phase II study of pemetrexed (P), cisplatin (C), and bevacizumab (B) in patients (pts) with advanced malignant mesothelioma (MM).J Clin Oncol 27:15s, 2009 (suppl; abstr 7578)

nccn.org, Malignant pleural mesothelioma

Mesothelioma Surgery Options – pro

M Levin, MD — Tue, 19 Jun 2012 20:14:52 +0000

Mesothelioma is a cancer that is most often linked to asbestos exposure. It can involve the luing of the lung(pleura) or of the belly(abdomen but are also found on the lining of the abdomen, heart or testicles. Pleural and abdominal mesotheliomas are the most common. Treating mesothelioma surgically remains difficult because it spreads along surfaces of these linings.

To perform surgery, accurate tumor staging is imperative since many patients in later stages of the disease are not candidates for some of the more radical approaches.

There are generally two surgical categories for the treatment and management of mesothelioma, cytoreductive (which aims to cure) and palliative (which aims to relieve symptoms).

Cytoreductive Surgery

Cytoreductive surgeries are radical and invasive techniques that focus on removing all of the cancer. These types of surgeries are only recommended for patients who are in good health and diagnosed with stage I or stage II mesothelioma. Some forward looking surgeons use the Sugarbaker technique which removes all cancer as well as the lining itself.

Extrapleural pneumonectomy (EPP) has been a standard treatment for pleural mesothelioma for many years. EPP involves the removal of the entire lung, diaphragm and pericardium. The diaphragm and pericardium are reconstructed synthetically after removal.

In studies so far, if aggressive surgery can be performed, five-year survival rates were as high was 46 percent.

Pleurectomy/Decortication (P/D) also involves surgically removing tumors. However, the lung is left mostly intact. Improved pulmonary function results in a lower mortality rate over EPP, but P/D has a slightly higher level of tumor recurrence. Postoperative radiation therapy is also limited because of the intact lung.

Both EPP and P/D are extremely invasive and the risk of morbidity and mortality are present for both procedures. Medical controversy still surrounds which procedure is more effective. More studies have yet to compare the effectiveness of these surgeries to systemic therapy and symptom control.

Palliative Surgery

Palliative surgery is a more conservative treatment. It focuses on the prevention and management of pleural effusion (fliud in the lining of the lungs) and tumor debulking to relieve chest pain and allow lung expansion. Debulking means removing the bulk of the cancer but not to attempt to remove it all. For patients in later stages of the disease, palliative treatment offers relief from symptoms and prolonged survival.

Other procedures such as pleurodesis can relieve symptoms by surgically inserting a talc mixture to close the pleural space and remove the place where fluid can accumulate. A permanent chest drain can also be inserted to prevent the build-up of fluid.

Though surgery remains an option for the treatment of mesothelioma, many expperts advocate an aggressive multimodal approach that uses chemotherapy and radiation together with surgery, in an attempt to improve on long term results.

Sources:

Mott, F. E. (2012). Mesothelioma: A review. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22438785

Tannapfel, A. (Ed.). 2011. Malignant mesothelioma: Recent results in cancer research. New York: Springer.

Read the Layperson version here.