Mesothelioma and SS1P Therapy – Some Promise

Delivering a continuous dose of a new immunotoxin therapy, SS1P, is safe and shows some effectiveness against mesothelioma and other mesothelin-positive cancers. However, the drug doesn’t appear to be any more effective when given by continuous infusion than in several intermittent doses, according to a recent study published in the journal, Clinical Cancer Research.

Some types of cancer, including mesothelioma, ovarian, and squamous cell cancers, display a protein called mesothelin in larger-than-normal amounts. Researchers are using this unique characteristic to develop new treatments for these cancers.

One potential new treatment, called SS1P, is an immunotoxin—an antibody attached to a toxic substance that binds to and kills mesothelin-positive cancer cells like mesothelioma. “SS1P contains an antibody fragment which binds to mesothelin specifically, so it will selectively kill mesothelin-expressing tumors,” explains lead author Robert J. Kreitman, MD, Chief of the Clinical Immunotherapy Section in the Laboratory of Molecular Biology at the National Cancer Institute.

In a previous study of SS1P, researchers gave cancer patients the therapy in several intermittent doses (bolus infusion). Dr. Kreitman and his colleagues wanted to determine whether giving the drug by continuous infusion might provide mesothelioma and other cancer patients with more constant levels of SS1P, thereby improving its effectiveness.

Twenty-four patients with mesothelioma, ovarian cancer, and pancreatic cancer were given a continuous infusion of SS1P over 10 days. Some of the participants also received additional cycles of the treatment.

At the end of the study, only one patient had a partial response to treatment (defined as improvement of more than 50%). Twelve patients had stable disease (some had improvement of less than 50%), and in 11 patients the cancer worsened.

Overall, therapy with SS1P was generally safe. The most common side effects were swelling caused by fluid build-up (edema), fatigue, weight gain, nausea, fever, low blood pressure, and allergic rash.

Although the mesothelioma, ovarian cancer, and pancreatic cancer patients tolerated the treatment well and one had a partial response, the results were not dramatic enough to indicate that continuous infusion of SS1P has any real advantage over one large bolus dose. This may be because after bolus dosing SS1P stays in the blood for more than a day, allowing it to work for a long period of time, says Dr. Kreitman.

“The antitumor response in this study overall was low, although it was a phase 1 single-agent study using SS1P alone,” he says. “We believe that combination treatment with SS1P plus chemotherapy may be more useful, and that is being tested now.”

Dr. Kreitman’s colleagues, Raffit Hassan and Ira Pastan have launched a phase II study looking at the effects of adding two chemotherapy drugs (pemetrexed plus cisplatinum) before SS1P treatment. The hope is that chemotherapy will provide a better distribution of SS1P to tumor cells, and improve the response against mesothelin-expressing cancers like mesothelioma.

Sources:

Kreitman RJ, Hassan R, FitzGerald DJ, Pastan I. Phase I trial of continuous infusion anti-mesothelin recombinant immunotoxin SS1P. Clin Cancer Res. 2009;15(16):5274-5279.

Hassan R, Bullock S, Premkumar A, Kreitman RJ, Kindler H, Willingham M, Pastan I. Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus I.V. infusion for patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers. Clin Cancer Res. 2007;13(17):5144-5149.