Role of Multimodality Treatment of Malignant Pleural Mesothelioma

Since 2004 the only FDA-approved treatment for mesothelioma has been a chemotherapeutic regimen of pemetrexed and cisplatin. However, the best treatment for surgery-eligible mesothelioma patients remains a multimodal treatment approach including surgery, chemotherapy, and radiation.
                                                   
The following analysis by Dr. Robert Cameron (David Geffen School of Medicine, UCLA, Los Angeles) of multimodal treatment versus chemotherapy alone provides a powerful argument for patients to consult with a surgeon as well as with an oncologist. Leading mesothelioma surgeons Dr. Kemp Kernstine (City of Hope, Los Angeles), Dr. Dan Miller (Emory University School of Medicine, Atlanta), and Dr. Eric Vallières (Swedish Cancer Institute, Seattle) support the following analysis. 

The Role of Multimodality Treatment of Malignant Pleural Mesothelioma

• Every year about 3000-4,000 patients are diagnosed in the U.S. with malignant pleural mesothelioma.1 In 2004, the FDA approved the first chemotherapy drug combination for the treatment of malignant pleural mesothelioma. The combination of cisplatin and pemetrexed (Alimta®) has since been aggressively marketed as the standard treatment in this disease.

• The Phase III randomized pemetrexed/cisplatin trial showed only a 41% partial response rate and a 12.1 month median survival rate, approximately three months longer than patients who were treated with cisplatin alone.2 This trial was performed specifically in patients who were not eligible for surgery.

• Since Alimta’s approval, many thoracic surgeons have observed a decline in the number of patients being referred for surgical treatment. At the same time, Medical oncologists have observed an increase in patients who pursue chemotherapy exclusively (on the recommendation of their medical oncologists). 

• Published data, while not randomized trials, show that the combination of surgery, radiation, and chemotherapy is almost always associated with the longest survival times for pleural mesothelioma patients who are eligible for surgery. The median survival of patients who receive multimodal therapy varies from 16 to 22 months,3 depending on the staging, type of surgery, cell type, as well as other factors.

• Many mesothelioma specialists believe that patients should consider surgery along with other therapies as part of a multimodality approach when the patient is a candidate for surgery.

• The best results are associated with multimodal therapy.4 Although the Eli Lilly study was designed specifically for patients who were not candidates for surgery, the results have been more broadly applied by medical oncologists to include many patients who are actually good candidates for surgically-based multimodality therapy, potentially compromising the care of this patient group.

• Surgery can remove gross mesothelioma tumor in up to 85% of patients (equivalent to a complete pathological response which is rare with cisplatin and pemetrexed. Adjuvant therapies, including chemotherapy and radiation can then be used to maintain a clinical remission. Furthermore, maintenance therapies, that can continue to suppress microscopic disease and forestall the tumor’s recurrence, as advocated by a few may provide even more long-term benefit.

• Treating and managing mesothelioma as a chronic illness acknowledges the refractory nature of the disease to all therapies and focuses on coping rather than curing.

• Chemotherapy is an important weapon in the treatment of malignant pleural mesothelioma. However, in patients who are otherwise eligible for surgery, it is probably best used in a well planned multimodality therapy regimen.  Medical oncologists should counsel their mesothelioma patients to consult with thoracic surgeons who have expertise in mesothelioma surgery, just as surgeons advise their patients to consult with a qualified medical oncologist about the potential benefits of adjuvant chemotherapy and radiation. Patients who are evaluated and treated in a defined multimodality therapy regimen by a multidisciplinary team of physicians, including surgeons, medical oncologists, and radiation oncologists   generally will be the most optimally managed and best served by their physicians. 

Supported by:

Dr. Robert Cameron, Director, Punch Worthington Lab, PHLBI
Dr. Eric Vallières, Surgical Oncologist, Swedish Medical Center
Dr. Kemp Kernstine, Thoracic Surgeon, City of Hope
Dr. Dan Miller, Thoracic Surgeon, Emory University School of Medicine

FDA's Approval of Eli Lilly's Alimta By Dr. Robert Temple February 4, 2004

FDA News Release: First Drug for Rare Type of Cancer February 5, 2004

Pemetrexed (Alimta) Description Instructions for use