A Promising Treatment for Patients with Rare Mesothelioma Subtypes

Mesothelioma is a rare disease, representing only 0.3% of all diagnosed cancer cases in the U.S. While the vast majority of tumors contain epitheloid cells, there are two other subtypes of cancerous cells which might occur with mesothelioma: sacromatoid and biphasic. Although the prognosis of mesothelioma is generally poor, as this form of cancer is highly resistant to treatment, sacromatoid and biphasic tumors are even less responsive to chemotherapy and also tend to spread more rapidly.

However, a recent study suggests that a combination of standard chemotherapy and the anti-cancer enzyme ADI-PEG20 might significantly improve the prognosis of sacromatoid and biphasic mesothelioma patients. The study was conducted by a group of mesothelioma researchers from the United Kingdom with the purpose of determining the safest and most effective dose of ADI-PEG20. Out of the nine study participants, five were suffering from pleural mesothelioma with sacromatoid or biphasic cells, while the other four had been diagnosed with non-small cell lung cancer. None of them had undergone chemotherapy prior to treatment.

The patients received a dose of ADI-PEG20 every week, with the amount of medication increasing gradually. At the same time, they began chemotherapy with cisplatin and pemetrexed, two drugs which are effective for both mesothelioma and lung cancer. 78% of the participants (seven patients) had a partial response after this treatment combination. Additionally, no one experienced toxicity and out of the 38 side effects observed during the study, only 9 had been caused by ADI-PEG20. The most common side effects of the anti-cancer enzyme were:

• rash
• tenderness, discomfort, redness, itching or pain at the site of injection
• fatigue

The ADI-PEG20 was developed by Polaris Group and works by decreasing essential amino acid levels in cancer tumors with argininosuccinate synthetase 1 (ASS1) deficiency. ASS1 is a key enzyme in the synthesis of arginine and malignant cells which do not express it are required to obtain arginine from the circulation in order to survive. Because ADI-PEG20 depletes arginine in the circulation, deficient cancer cells will eventually die, while healthy cells remain intact.

A weekly dose of 36 mg of ADI-PEG20 in conjunction with three chemotherapy cycles has proved to be very beneficial for patients with sacromatoid and biphasic pleural mesothelioma. “In this biomarker-selected group of patients with ASS1-deficient cancers, clinical activity was observed in patients with poor-prognosis tumors”, says lead researcher Emma Beddowes of Cambridge University.