Researchers in London have developed a new way of categorizing patients with advanced malignant mesothelioma that allows them to predict who will benefit the most from participation in a Phase I clinical trial.
The Drug Development Unit at the Royal Marsden Hospital already uses a prognostic scoring system for cancer patients to determine which patients would be good candidates for Phase 1 clinical trials of new treatments.
The RPS, as it is called, is based on the level of a blood protein called albumin, the number of disease sites, and the lactate dehydrogenase (LDH) level.
Choosing Good Mesothelioma Trial Candidates
But because of the unique way in which malignant mesothelioma forms and grows, and because it often stays localized for longer than other cancers before spreading to other parts of the body, the team determined that mesothelioma patients needed their own prognostic scoring scale.
To come up with a special Phase I trial candidacy scale specifically for people diagnosed with advanced mesothelioma (the m-RPS), the research team evaluated the results of 38 Phase I trials between 2003 and November 2015.
For each treatment, efficacy was assessed based on the patients’ response rates, how long they survived before their mesothelioma relapsed, and overall survival.
Mesothelioma Patients and Phase I Trials
Among the 65 patients with advanced mesothelioma who were included in the retrospective study, the median time to relapse (called progression free survival or PFS) during a Phase I trial was 2.5 months and overall survival was 8 months.
“The m-RPS was developed comprising of three different prognostic factors: a neutrophil:lymphocyte ratio greater than 3, the presence of more than two disease sites, and albumin levels less than 35 from the MVA,” writes study author Dionysis Papadatos-Pastos, MD, a medical oncologist with University College London Hospitals.
The researchers assigned one point for each of these three factors. Mesothelioma patients in a Phase I trial who had only one of the factors had a median overall survival of 13.4 months, whereas those with scores of two or three factors had a median overall survival of just four months.
Most mesothelioma patients experienced some toxicity during their Phase I trial but 28 percent of patients had more serious complications.
Phase I Clinical Trials Good for Most Patients
Most of the patients involved in a Phase I clinical trial for advanced mesothelioma tolerated the treatments well and showed signs of antitumor activity.
Dr. Papadatos-Pastos says using the m-PRS criteria will allow him and other oncologists to select the most suitable candidates for future mesothelioma clinical trials. The study concludes with the suggestion that the m-RPS be prospectively validated.
Advanced mesothelioma patients are often encouraged to consider participating in a clinical trial because there are few viable mesothelioma treatments available. Mesothelioma is caused by exposure to asbestos and is highly resistant to conventional cancer therapies.
Papadatos-Pastos, D, et al, “Clinical outcomes and prognostic factors of patients with advanced mesothelioma treated in a phase I clinical trials unit”, February 16, 2017, European Journal of Cancer, Epub ahead of print