Surgery and chemotherapy represent the two most commonly delivered treatments for patients with any form of mesothelioma. While no single cure exists for this difficult disease, continuous research into improving both modalities has led to real, if still small, improvements in quality of life and overall survival time. The development of pemetrexed, marketed as Alimta® by Eli Lilly, has proven to be a watershed development in the treatment of mesothelioma. In 2004 the USFDA approved pemetrexed with the platinum compound cisplatin for the treatment of pleural mesothelioma. Since then, Alimta therapy has become the chemotherapy standard of care in the US and around the world for mesothelioma. However, the combination is known to be quite difficult to tolerate for patients with low performance scores or for those, such as the elderly, with other physical weaknesses. Because of this, scientists have been studying pemetrexed in combination with other platinum agents. Researchers from Italy have recently released their report on the use of pemetrexed with carboplatin, which is a cisplatin analogue with a lesser toxicity profile.

Introduction to the Study

The researchers enrolled 76 chemo-naive patients with histologically-proven mesothelioma in their study. Patients were included who were under 75 years old and who had measurable disease on a CT scan. Performance status had to be two or under and they must never have received prior systematic chemotherapy or had a prior cancer (excepting non-melanoma skin cancer or cervical canner in situ). There were 54 males and 22 females, with an average age of 65. Histologically, there were 57 cases of epithelial mesothelioma, 13 biphasic cases and 3 sarcomatous cases.

The study was classified as a phase II study whose primary endpoint was to evaluate the tumor’s response to the treatment. Secondary analyses included overall survival, treatment toxicity and time to progression.

Results

Three patients were classified as having a complete response, meaning all known disease had disappeared completely, and 16 patients were classified as partial responses, which means they had at least a 30% decrease in tumor burden. The combination of these two categories gives an overall tumor response rate of 25%. 29 patients were reported as having stable disease, where tumor burden was relatively unchanged (less than 30% in volume decrease or less than 20% in volume increase) while 28 others had progressive disease, which mean that tumor burden increased more than 25%.

Overall survival averaged 14 months and the median time to progression was 8 months.

As regards toxicity, the most common events were neutropenia and thrombocytopenia. The former is a potentially serious condition where an abnormally low level of an important type of white blood cell (a neutrophil) reduces the body’s ability to fight off infection, while the latter refers to a condition with an abnormally low level of blood platelets, which are an important factor in blood clotting. Overall though, the treatment was well-tolerated by most patients.

Conclusion

The authors of the study conclude that the combination of pemetrexed plus carboplatin could be an important option for the treatment of mesothelioma. While pemetrexed plus cisplatin is, and will likely remain, the chemotherapy standard of care, its toxicity profile is greater than some types of patients are able to handle and in those cases, substituting carboplatin may be the correct treatment for those patients.

Labels: mesothelioma