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Extending Mesothelioma Survival with Chemotherapy

ByAlex Strauss

In the continued quest to improve the effectiveness of chemotherapy treatment for malignant pleural mesothelioma, two new studies have been published this week on the effectiveness of adding additional drugs to the standard combination.

The majority of patients who receive a mesothelioma diagnosis will have treatment that includes chemotherapy. According to data from the National Cancer Institute’s SEER database, the chemotherapy regimen prescribed most often for mesothelioma is a combination of pemetrexed (Alimta) and cisplatin or carboplatin. Approximately 67 percent of mesothelioma patients who receive chemotherapy have this combination.

Unfortunately, even the standard chemotherapy combination has not been shown to extend mesothelioma survival by more that a few months. Scientists are continually looking for ways to make it more effective.

Attacking Mesothelioma Tumors at the Vascular Level

One recently tested approach involved adding an experimental drug called NGR-hTNF to the mix. NGR-hTNF in a novel therapeutic agent that specifically targets tumor blood vessels. In addition to being fast-growing, mesothelioma tumors are highly vascularized.

The theory is that disrupting the blood flow that feeds a mesothelioma tumor could make it more susceptible to attack with chemotherapy drugs.

 

In a double blind, placebo-controlled, phase 3 trial conducted at 41 centers in 12 countries, doctors gave NGR-hTNF to 400 mesothelioma patients whose cancer had come back after standard chemotherapy.

The drug was given weekly by infusion along with one of several different chemotherapy drugs (gemcitabine, vinorelbine, or doxorubicin), at the doctor’s discretion.

Although NGR-hTNF did not cause any more serious side effects or deaths than the other chemotherapy drugs, it also did not appear to extend survival.

“At the cutoff date, the median follow-up was 18.7 months and overall survival did not differ between the two treatment groups (median 8.5 months in the NGR-hTNF group vs 8 months in the placebo group),” states the report summary published online by Lancet Oncology this week.

Gemcitabine May Work Better During Surgery

Another drug getting attention from the mesothelioma community this week is gemcitabine and the news appears to be somewhat better. Gemcitabine (Gemzar) is most often used to treat cancer of the bladder, ovary, breast, pancreas and non-small cell lung cancer.

In the new study, renowned mesothelioma surgeon Dr. David Sugarbaker of Baylor College of Medicine, along with colleagues  at Brigham and Women’s, Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center in Boston, added gemcitabine to cisplatin as part of  heated intraoperative chemotherapy (HIOC) for pleural mesothelioma patients.

During HIOC, a solution of chemotherapy drugs is rinsed through the chest following surgical resection of a malignant pleural mesothelioma tumor in order to kill residual cancer cells and keep new tumors from developing.

One hundred and forty-one patients were enrolled in the trial, which involved escalating the dose of gemcitabine to find the maximum tolerable dose (MTD). After two patients developed Grade 3 leukopenia (a reduction in white blood cells) at 1100 mg/m2 of gemcitabine, researchers set the MTD at 1000 mg/m2 of gemcitabine with 175 mg/m2 of cisplatin.

Median overall recurrence-free survival was 20.3 months among those who had HIOC with gemcitabine following EPP surgery and 10.7 months following lung-sparing P/D surgery.

The report concludes that the cisplatin/gemcitabine HIOC combination “can be administered safely and feasibly in the context of complete surgical resection of malignant pleural mesothelioma by EPP or P/D.” It appears in the latest issue of the Journal of Thoracic Surgery.

Sources:

Gregorc, V, et al, “NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial”, May 9, 2018, Epub ahead of print

Burt, BM, et al, “A Phase I Trial of Surgical Resection and Intraoperative Hyperthermic Cisplatin and Gemcitabine for Pleural Mesothelioma”, Mary 9, 2018, Journal of THoracic Oncology, Epub ahead of print

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