The chemotherapeutic treatment of mesothelioma is one of the major arms of contemporary mesothelioma research. A wide variety of investigations into new agents and treatment regimens are currently being conducted in hospitals and laboratories around the world. Even as the last few years have seen major advancements in the effectiveness of a number of mesothelioma treatments, the reality of the situation is that mesothelioma is still without cure. As impressive and welcome as the extension in median survival times are for patients and their families, physicians know that more work is required before the treatment of pleural mesothelioma and peritoneal mesothelioma will be seen within the same framework of successful therapies that other cancers are now seen within.

One of the newer chemotherapy agents that is increasingly being studied for the treatment of mesothelioma is vinorelbine, which is a member of the class of chemotherapy drugs known as vinca alkaloid agents. These drugs disrupt the mitosis phase in the cell cycle. Previous vinca agents were not active in the treatment of mesothelioma, but a number of recent studies have indicated that vinorelbine is not only active in the treatment of mesothelioma, but may be among the most active in terms of overall response rate.

To further investigate the efficacy of vinorelbine, researchers from Denmark conducted a study on its use with that of cisplatin as first-line chemotherapy in the treatment of pleural mesothelioma. They have recently published their results in the journal British Journal of Cancer.

Overview of the Study

The combination of vinorelbine and cisplatin has shown activity in the treatment of the non-small cell lung cancer, so the researchers were interested if the combination would be similarly active for pleural mesothelioma. Platinum agents, such as cisplatin, have already been shown to be active in the treatment of mesothelioma and are a part of the major chemotherapy standard of care for pleural mesothelioma, which is combination therapy using pemetrexed (Alimta) and cisplatin (or carboplatin).

To conduct their study, the researchers enrolled patients with histologically-proven pleural mesothelioma, who were not eligible for surgery and had not previously completed a chemotherapy regimen, among other requirements. The treatment dictated cisplatin every four weeks, with standard antiemetic therapy, and weekly vinorelbine administrations. The patients were monitored on a number of fronts for treatment response, as well as side effects and toxicity.

Results

A total of 54 patients were treated with the vinorelbine + cisplatin regimen. There were 46 males and 8 females. The breakdown of the histological subtypes of the disease were as follows: 40 patients presented with epithelial mesothelioma, 5 with sarcomatous mesothelioma and 9 presented with biphasic mesothelioma. Most of the patients were Stage III or Stage IV patients and the median age was 63 years old.

Of the full patient class, there were 14 partial responses and 2 complete responses, for an overall response rate of almost 30%. Of the 40 cases of epithelial mesothelioma, 13 patients demonstrated some response, while two patients with the sarcomatous subtype had a response and one with the biphasic response. Four of the eight women showed some response to treatment, while only 12 of the 46 men showed a response. The median survival time was 16.8 months, with a one-year survival figure of 61% and a two-year figure of 31%.

However, the authors note that a number of patients experienced significant side effects or some form of toxicity event. Even as the response rate of the procedure was more active as compared to some other treatments, the side effects experienced by the patients were also greater than those who’ve been studied with other regimens—including pemetrexed/cisplatin combination therapy.

Conclusion

The response rate figures show that the vinorelbine + cisplatin regimen is among the most active in the treatment of pleural mesothelioma. However, the authors state they are unable to recommend the treatment course for a number of important reasons. Even though their study demonstrated the efficacy of the regimen, they feel that precise comparisons between previous studies are not possible do to differences in the patients enrolled and the methodologies used to compare responses. Along with the high percentage of side effects associated with the therapy, they also feel that the weekly administration of vinorelbine makes it impractical to recommend this particular regimen of treatment.

However, the authors are hopeful regarding the future use of the treatment and state that improvements in the delivery mechanisms of vinorelbine, as well as other improvements in the overall treatment regimen, may be helpful in overcoming these issues. They also state that vinorelbine + cisplatin would be an excellent candidate in the use of induction chemotherapy before surgery.

Labels: chemotherapy, cisplatin, mesothelioma, treatments, vinorelbine