Malignant mesothelioma is a rare, asbestos-linked cancer of internal membranes. Although all forms are highly resistant to standard cancer therapies, the sarcomatoid and biphasic subtypes – which are the rarest forms of mesothelioma – typically carry the worst prognosis.
But a group of UK mesothelioma researchers now say an anticancer enzyme called pegylated arginine deiminase (ADI-PEG20) may improve chemotherapy outcomes for a particular subset of people with malignant pleural mesothelioma.
How Does It Work?
ADI-PEG20 depletes essential amino acid levels in tumors that do not express argininosuccinate synthetase 1 (ASS1), a key enzyme in the synthesis of arginine. ADI-PEG20 can be toxic for these ASS1-negative tumors.
Tests of the enzyme in other cancers have shown it to have antitumor activity and tolerable side effects for patients.
ADI-PEG20 + Chemotherapy for Mesothelioma
To test the impact of ADI-PEG20 on ASS1-negative mesothelioma tumors, researchers administered the enzyme to nine cancer patients who had not yet had chemotherapy, including five people with malignant pleural mesothelioma and four with non-small cell lung cancer. The goal of the study was to determine the safest effective dose of ADI-PEG20 in these patients.
Study subjects received weekly doses of ADI-PEG20 that gradually increased each week. At the same time, these mesothelioma patients and lung cancer patients received standard chemotherapy with pemetrexed (Alimta) and cisplatin.
Patients whose mesothelioma tumors stopped growing after a maximum of six chemotherapy cycles were allowed to continue on ADI-PEG20 until their cancer progressed or they withdrew from the study for another reason.
Mesothelioma Treatment Response
Of the 38 “adverse events” reported by patients, nine were determined to be the result of the ADI-PEG20 treatment. Even so, none of the patients were forced to leave the study because of toxicity.
Seven of the nine patients (78%) experienced a partial response to the combination treatment, including three patients with either sarcomatoid or biphasic malignant pleural mesothelioma.
“In this biomarker-selected group of patients with ASS1-deficient cancers, clinical activity was observed in patients with poor-prognosis tumors,” concludes lead researcher Emma Beddowes of Cambridge University. To improve the outlook for these patients, Beddowes and her colleagues recommend a weekly dose of 36 mg of ADI-PEG20 plus three rounds of chemotherapy with cisplatin and pemetrexed.
Beddowes, E, et al, “Phase 1 Dose-Escalation Study of Pegylated Arginine Deiminase, Cisplatin, and Pemetrexed in Patients With Argininosuccinate Synthetase 1-Deficient Thoracic Cancers”, April 7, 2017, Journal of Clinical Oncology, Epub ahead of print