Combination Chemotherapy

Various combination chemotherapy regimens have been reported to have higher response rates in small phase II trials. Raltitrexed combined with oxaliplatin has also been shown to be effective, and gemcitabine--applied as a single agent or in combination with cisplatin--as well as vinorelbine appear to improve quality of life in patients presenting with mesothelioma. The most active and best-studied drug combination for the treatment of mesothelioma that has emerged is the combination of Alimta and Platinol® (cisplatin) and will probably be adopted as a “standard” for comparing other treatments. The only phase III randomized study of chemotherapy for mesothelioma ever performed was the comparison of Alimta® and cisplatin to cisplatin alone.

Alimta® and Platinol® (cisplatin)
In this study, a total of 456 patients were enrolled from April 1999 to March 2001. Patients were randomized to receive either the combination Alimta® and cisplatin or cisplatin alone. Patients treated with the Alimta®/cisplatin combination lived longer (12 months vs. 9 months) and experienced a longer time gap before the cancer progressed. The average survival and time to cancer progression was further improved by giving a vitamin supplementation of B12 and folic acid. In addition to a longer survival time and the ability to control the disease, patients assigned to the Alimta® /cisplatin combination reported an improvement in quality of life and symptom relief (including pain, shortness of breath, fatigue, weight loss and cough) when compared with cisplatin alone.

While many regimens are being tested for the treatment of mesothelioma, there is still room for development of new agents or combinations of agents. Currently, the addition of Gemzar® to Alimta® is being evaluated in clinical trials and could be compared to Alimta® and cisplatin or Alimta® and Paraplatin®. Other combinations, including cisplatin and gemcitabine, have also shown encouraging response rates and clinical activity.

Targeted agents, developed through a better understanding of the biology of the disease either used alone or as part of multimodal therapy, may provide major clinical advances in the next few years. Studies are also underway for second line chemotherapy treatment regimens for those patients who fail chemotherapy the first time.

Patients evaluated at the Brigham and Women’s Hospital and Dana-Farber Cancer Institute are offered multiple treatment options. Patients are offered chemotherapy alone. If eligible for surgery, patients will be offered a combined modality approach, including surgery, chemotherapy and radiation. Our most important consideration is to tailor the best treatment for every patient.