The search for more effective treatment regimens is probably the most active area of current mesothelioma research. Even as our overall knowledge of the disease has increased during the last few years, it has only had a limited effect on the efficacy of the available treatments—increasing their effectiveness in degree, but not really in kind. Mesothelioma, especially its most common form, pleural mesothelioma, still ranks among the most difficult of all cancers to treat. While peritoneal mesothelioma, which is the second most common form of the disease, often presents with a better prognosis than does the pleural form, its historical survivability figures have also been disappointing.

In terms of total number of diagnoses, peritoneal mesothelioma accounts for somewhere between twenty and twenty-five percent of all mesothelioma diagnoses. The FDA has not yet recommended a standard of care for its management and all of the current treatment modalities and staging guidelines for mesothelioma have been developed for pleural mesothelioma. In response to this situation, a number of treatments specific to the peritoneal form have been proposed and some of them have demonstrated excellent results in small-scale studies. Doctors from the Columbia University Medical Center in New York City have recently released the results of a study they conducted for the treatment of peritoneal mesothelioma and their findings are quite promising. Utilizing a comprehensive, multimodal treatment regimen that incorporated surgery, multiagent intraperitoneal chemotherapy and radiation of the entire abdomen, they achieved a median overall survival of 70 months and demonstrated a three-year survival figure of 67%.

This article is a description of their study and findings.

Overview of the Study

The study enrolled 27 patients with histologically-confirmed peritoneal mesothelioma. Patient requirements included good performance status (identified as a Southwest Oncology Performance Status of 0 or 1), life expectancy greater than 2 months, no prior radiation therapy and up to two previous systematic chemotherapy regimens or 1 intraperitoneal chemo treatment. The average age of the patients was 53, with the youngest at 31 and the oldest at 75. There were twenty males and seven females. Histologically, 23 patients presented with epitheloid mesothelioma, while 4 presented with sarcomatoid mesothelioma.

The study defined a single primary endpoint and two secondary endpoints. The primary endpoint was overall survival. The doctors were interested in how effective the treatment was for the actual lifespan of the patient and they defined this figure as “the time from consent until death from any cause or last follow-up.” Of the secondary endpoints, the first was disease-free survival, defined as “the time from consent until diagnosis of recurrent disease, death from any cause, or last follow-up,” and overall safety.

The treatment protocol involved abdominal surgery (laparotomy) with omenectomy (removal of the omentum, the fatty tissue that surrounds the peritoneum) and the removal of all visible malignant tissue greater than 0.5cm in thickness. A few weeks after the surgery, chemotherapy was begun. The first chemo regimen involved weekly intraperitoneal infusions of cisplatin that alternated with doxorubicin administration. This continued over eight weeks, so each agent was delivered a total of four times. After this dosing scheme was completed, the next phase of chemotherapy, involving intraperitoneal infusions of gamma interferon-1b, was begun. During the first week of treatment, nine million units were delivered twice. The dose was increased to thirty million units twice a week for the next three weeks. A few weeks after completing interferon administration, another laparotomy was performed to examine the effectiveness of the treatments. If residual tumor tissue was present and deemed resectable, surgery was once again performed to remove the tissue. If no tissue was present or only small nodules, another round of chemotherapy was begun. This time, heated chemo using mitomycin and cisplatin were delivered. For patients whose laparotomy identified tissue that was malignant and non-resectable, systematic chemotherapy was considered instead of the heated intraperitoneal chemotherapy.

For patients who completed both second round surgery and intraperitoneal chemotherapy, whole abdomen radiation was the next, and final, stage of treatment. Total radiation dose was 3000 or 3080 cGy, i.e., the standard unit of measure for radiation used for medical purposes, with kidney blocks utilized after 1400–1550 cGy.

Results

The overall results of the study as presented were excellent.

Median overall survival for the entire group was 70 months, with a three-year survival figure of 67%. Median disease-free survival for the whole group was listed at 30 months, with a 50% three-year probability of survival figure. As expected, there was a significant difference between the cohort who presented with epitheloid mesothelioma and the one who presented with sarcomatoid mesothelioma. The epithelial group had a three-year probability of survival figure of 78%, while none of the patients from the other group survived longer than 11 months.

Other grouping structures revealed findings in line with other studies. Patients with bulky disease are considered to have a worse prognosis than patients with a smaller tumor burden and this study confirmed this as well. The five-year probability of survival figure for those with bulky disease was only 50%, while those without bulky disease demonstrated a five-year figure of 75%. While women were identified as responding to treatment as slightly better than men were, controlling for the four cases of sarcomatoid mesothelioma (all of whom were men) effectively removed the gender difference.

Conclusion

The results of this study clearly demonstrate that treatments for peritoneal mesothelioma are improving for at least some types of patients. While much more research is still needed to verify these results, the overall efficacy of the treatment regimen as presented in this study is quite promising and certainly deserves more study.

Labels: mesothelioma