Promising Medicines to Try
words by mary ann littell /
photograph by lynz photography
ark N. Stein, MD, is working on a number of clinical trials, including a Phase I study combining patupilone, a potent inhibitor of cell division, with an oral medication known as an mTOR inhibitor, which works by slowing cell growth. It is the first time this combination is being studied. The goal is to determine the correct dose of the two medications in combination and to learn more about their side effects. “In the process, many patients with advanced cancer who have been treated with other chemotherapy drugs have access to medications they otherwise would not be able to obtain, as these drugs are not yet FDA-approved,” says Stein. CINJ is the only site for this Novartis-sponsored study. The combination is of interest for a number of tumors, including those of the prostate and colon.
Stein is working with Merck on a Phase I trial combining two drugs that target the PI3 kinase pathway, an essential pathway in cancer progression. They are using an antibody to the insulin-like growth factor receptor that blocks this receptor at the cell surface and combining it with another mTOR inhibitor. The combination may be effective in treating sarcomas, breast and prostate cancer.
Stein is also conducting trials for kidney, bladder and prostate cancer. “A number of new drugs for kidney cancer work by blocking blood vessel growth or by inhibiting mTOR,” says Stein. In a recently opened trial, an FDA-approved drug (Sutent) is being combined with a novel type of immune therapy know as donor lymphocyte infusion, where white blood cells from a first-degree relative (child, sibling,
parent) are given along with Sutent.
In bladder cancer, CINJ has just opened a trial for patients with untreated metastatic bladder cancer that combines the most commonly used combination in bladder cancer (gemcitabine and cisplatin) with sorafenib.
Stein is the lead CINJ investigator in the recently opened Phase III clinical trial, “Study of Active Surveillance Therapy Against Radical Treatment in Patients Diagnosed with Favorable Risk Prostate Cancer,” also known as the START trial. Researchers hope to accrue more than 2,100 participants from the U.S., Canada and Europe for this international study, including 60 from CINJ. Patients with early-stage prostate cancer will undergo either the usual standard of treatment (radiation therapy or prostate removal) while the other group will receive what is known as active surveillance, in which their disease will be monitored closely. Recent studies from CINJ investigators have shown that there are benefits to active surveillance, since it avoids the risk of treatment side effects. The study is expected to take five years to complete.