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Recently at the American Society of Clinical Oncology’s (ASCO) 2015 annual meeting, Dr. Gerald Zalcman reported the results of a study on a new mesothelioma treatment that has the potential to improve survival rates for malignant pleural mesothelioma patients.
Dr. Zalcman presented the results of the French Cooperative Thoracic Intergroup MAPS study that compared two related treatments for the response rates against mesothelioma. The results have the potential to change the standard of care treatment protocol for mesothelioma patients, but more extensive study is needed.
Because not all mesothelioma patients benefit from the standard of care chemotherapy regimen, physicians continue to investigate other combinations. They are looking for new combinations or types of therapies that:
- Improve the number of patients that respond
- Block cancer growth for more months or years (progression-free survival)
- Increase the length of overall survival of all patients so that the median overall survival increases
Explaining the Bevacizumab Study
Dr. Zalmach studied two groups of mesothelioma patients. The study followed most patients for greater than 3 years (median follow-up time 39.4 months). They enrolled 448 mesothelioma patients, all with relatively good health. Different types of mesothelioma were evenly divided among the treatment groups.
One control group received the standard of care chemotherapy combination treatment of Alimta and cisplatin. The second experimental group received the same Alimta and cisplatin treatment and a third drug called bevacizumab.
Bevacizumab, an anti-angiogenic drug, blocks the ability of cancer to stimulate the growth of blood vessels. Without more blood vessels, the cancer can’t grow because it is essentially starved. Bevacizumab inhibits cancer by blocking its food supply whereas chemotherapy directly blocks its ability to make more DNA and cells.
Standard of Care Control Group
Clinicians treated 225 mesothelioma patients in the control group with the standard of care regimen, pemetrexed and cisplatin. The patients received chemotherapy on day 1 of a three week cycle for six cycles. About 3 of every 4 patients received the full 6 cycles of chemotherapy.
The pemetrexed and cisplatin group had a median overall survival of 16.1 months, similar to previous studies.
Standard of Care and Bevacizumab Experimental Group
Clinicians treated 223 mesothelioma patients with bevacizumab on day 1 of each of the six chemotherapy cycles. The mesothelioma patients also received pemetrexed and cisplatin on day 1 of each chemotherapy cycle. Most patients (75%) received the six cycles of the treatments.
Positive Results from Experimental Group
The bevacizumab-pemetrexed-cisplatin treatment group significantly increased the median overall survival from 16.1 months (control) to 18.8 months. The triple combination also significantly delayed the restarting of the growth of mesothelioma for a median time of 9.6 months progression-free survival. In comparison, mesotheliomas in the control group began regrowing sooner, with a median of 7.5 months progression-free survival.
Drawbacks of Triple Treatment Regimen
The side effect profile of bevacizumab was similar to previous studies in mesothelioma 1,2 and other cancers, including non-small cell lung cancer, pancreatic cancer, prostate cancer, colon cancer, and ovarian cancer.3,4
The mesothelioma patients treated with bevacizumab-pemetrexed-cisplatin group had significantly higher rate of hypertension (23%) versus those treated with the standard pemetrexed-cisplatin combination (1%). The experimental group with bevacizumab also had higher rates of blood clots (7%) than the group treated with the standard of care (1%). In addition, more bevacizumab treated patients showed excess bleeding and hemorrhage events (41%) than those treated with the standard of care (7%).
For these reasons, patients with mesothelioma, especially those with cardiovascular disease, should strongly consider the current standard of care, as it has a lower risk of fatal side effects related to the cardiovascular system.
Ceresoli GL, Zucali PA, Mencoboni M et al. Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma. Br J Cancer 2013;109(3):552-558.
Chen D, Li X, Zhao H et al. The efficacy of pemetrexed and bevacizumab intrapleural injection for malignant pleural mesothelioma-mediated malignant pleural effusion. Indian J Cancer 2014;51 Suppl 3e82-85.
Eveno C, Passot G, Goere D et al. Bevacizumab doubles the early postoperative complication rate after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol 2014;21(6):1792-1800.
Huang H, Zheng Y, Zhu J, Zhang J, Chen H, Chen X. An updated meta-analysis of fatal adverse events caused by bevacizumab therapy in cancer patients. PLoS One 2014;9(3):e89960.