Sarcomatoid Mesothelioma Responded to Trabectedin-Based Chemo

Encouraging news for sarcomatoid malignant pleural mesothelioma patients comes now from Italy. Researchers have found that the mesothelioma chemotherapy drug trabectedin kept nearly 30 percent of patients alive and mesothelioma progression-free for at least 18 weeks.

That may not sound like a long time, but it is if you have the sarcomatoid type of mesothelioma. Sarcomatoid mesothelioma is highly resistant to standard chemotherapy consisting of platinum combined with pemetrexed.

As a result, there is at present no suitable first-line chemotherapy treatment for sarcomatoid mesothelioma at present, so the researchers were justifiably excited about their observations with trabectedin.

Effectiveness Against Mesothelioma

As the researchers explained in a recent issue of the Journal of Clinical Oncology, trabectedin is an alkylating agent endowed with a response pattern that suggests it is akin to DNA repair mechanisms.

It has been shown to modulate cytokines, chemokines and growth-factor production by tumor-associated macrophages.

The researchers were intrigued by these attributes of trabectedin because the presence of cytokines, chemokines and growth-factor production by tumor-associated macrophages are all associated with inflammation — and inflammation is a fundamental characteristic of mesothelioma.

Trabectedin is not a chemotherapy drug normally used in Europe for treating mesothelioma. There, it’s used for patients with advanced soft tissue sarcomas.

Advanced soft tissue sarcomas don’t respond well to conventional chemotherapy. But they do respond to chemotherapy when trabectedin is in the mix.

That led the researchers to wonder if trabectedin would work against other tumors that are poorly responsive to conventional chemotherapy — sarcomatoid mesothelioma, for instance.

So the researchers put out a call for mesothelioma patients to participate in a study. It happened, though, that not all of the enrollees could be evaluated. The researchers ended up with 17. Fourteen were men, and the median age was 67.9 years.

Ten of the patients had stage IV mesothelioma. Six of them had stage III. The final patient was at stage II. Seven had never previously undergone chemotherapy.

The study was designed to include not just sarcomatoid mesothelioma patients, but also those with epithelioid mesothelioma and biphasic mesothelioma.

All of the patients received a 1.3 mg/m2 dose of trabectedin over a span of three hours. This occurred once every 21 days until the mesothelioma resumed progression or until the toxicity level became too much for the patient to handle.

At the end of 12 weeks, 41 percent of the patients were alive and free of progression. At the close of 18 weeks, the same could be said of 29 percent of them.

Mesothelioma Response Was Encouraging

The study had several aims. One of the most important was to assess the effects of trabectedin on mesothelioma inflammatory symptoms and pain.

Another important goal was to develop a stronger understanding of trabectedin’s activity on certain biological features of mesothelioma, such as macrophage activity.

The researchers came away feeling that they had accomplished these purposes. Also, they believed they had successfully refuted a hypothesis that suggested no more than 15 percent of sarcomatoid mesothelioma patients receiving trabectedin would be alive and progression-free beyond 12 weeks.

The researchers contend that the results of this study are “highly promising” and therefore further investigation into trabectedin as a mesothelioma chemotherapy agent is warranted.

One lesson they learned from this study is that the frequency of severe treatment-related hepatic toxicity means patients have to be chosen with great care. In the study, 58 percent of the patients experienced moderate hepatic toxicity event. Nearly all of those events registered at grade 3.

“Overall, trabectedin demonstrated its activity in terms of progression-free survival and may represent a valid treatment option for the sarcomatoid histotype of malignant pleural mesothelioma,” the researchers wrote.

The study was conducted under the auspices of ATREUS, an Italian multicenter single-arm phase II trial.