One of the most significant problems in the treatment of malignant mesothelioma is that the tumor can be resistant to many traditional forms of chemotherapy drugs. This drug resistance varies from patient to patient. Hence, weeks and even months of chemotherapy treatment could be wasted on a patient with malignant mesothelioma if that person’s tumor is particularly resistant to the type of drug being administered.
The International Mesothelioma Program (IMP) at Brigham and Women’s Hospital in Boston, Massachusetts is developing a new treatment aid that may assist physicians in prescribing the most appropriate form of chemotherapy for their mesothelioma patients. This tool is called the Extreme Drug Resistance (EDR) assay.
Extreme Drug Resistance (EDR) Assay
To do an EDR assay, physicians at Brigham and Women’s Hospital remove a mesothelioma tumor fragment during surgery (extrapleural pneumonectomy or pleurectomy/decortication) and send it to the laboratory of Oncotech, Inc. in Tustin, California. The cultured tumor is then tested against various chemotherapy drugs that are commonly prescribed for malignant mesothelioma. Brigham and Women’s Hospital has Oncotech expose the tumor to Cisplatin, Gemcitabine, a combination of Cisplatin and Gemcitabine, and Vinorelbine. As of now, Alimta, which is a drug frequently used to treat mesothelioma, cannot be used in the EDR assay, but the technical problems associated with Alimta in this test are being worked out, according to Dr. William Richards, Operations Director of the Brigham and Women’s Hospital Tissue and Blood Repository.
Oncotech then determines whether the mesothelioma tumor for that particular patient is resistant to each of the chemotherapy drugs or the combination of drugs. If the EDR assay shows that a cultured tumor is extremely resistant to a particular drug, then there is a 99 percent probability that the tumor in the patient will also be resistant to that drug or drug combination.
Next Step: Clinical Trial Testing
According to Dr. Gavin Gordon, co-director at the Brigham and Women’s Hospital Thoracic Surgery Oncology Laboratory, the EDR assay for malignant mesothelioma must still be tested in a clinical trial for it to be approved as part of the treatment protocol. There are case reports where the predictive value of the EDR assay has shown a very high correlation between the in vitro test and actual drug resistance in the patient.
In a published case report from the Kobe University Graduate School of Medicine in Japan, physicians used a test similar to the EDR assay called the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) to identify the correct treatment for malignant pleural mesothelioma in a 63 year old woman. The CD-DST test showed that the patient’s tumor was particularly sensitive in vitro to Gemcitabine and Vinorelbine. Based on this result, her physicians selected these chemotherapy agents for her treatment.
The EDR assay test could be an invaluable tool in the treatment of malignant pleural mesothelioma and peritoneal mesothelioma, diseases that have shown a wide variability in response to different chemotherapy agents.