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VCU Massey Cancer Center has developed and opened a Phase 1 clinical trial to study the effects of Viagra in combination with chemotherapy to treat patients with progressive, advanced solid tumors. The trial is a result of previous research conducted at Massey by a group of researchers including physician-scientist Andrew Poklepovic, M.D., who is the leading the trial as its principal investigator. Their research demonstrated that regorafenib (trade name Stivarga), a type of chemotherapy, interacts with Viagra (generic name sildenafil), a medication originally developed for erectile dysfunction, to kill tumor cells significantly better than regorafenib alone.

The trial is for patients with various forms of advanced cancer whose disease is growing despite already receiving standard treatment. Patients will take both medications orally for as long as there are no serious side effects and it is determined that their cancer has stopped growing. The goal is to explore the anti-tumor effects of the drug combination while determining the ideal dosages for future phases of clinical trials to further test the treatment’s efficacy. This trial is one of several studies at Massey that are ongoing or in development examining sildenafil’s interaction with other agents to overcome resistance to standard chemotherapies—combinations that have been proven effective in pre-clinical experiments. The researchers hope to enroll 29 patients in the trial and to complete it by 2017.

Sildenafil was approved by the Food and Drug Administration (FDA) in 1998 for the treatment of erectile dysfunction and approved for the treatment of pulmonary hypertension in 2005. A phosphodiesterase 5 (PDE5) inhibitor, sildenafil works to prevent PDE5—an enzyme that breaks down Cyclic guanosine monophosphate (cGMP)—from working too quickly. When PDE5 is blocked, cGMP levels increase to play a vital role in the regulation of blood flow, smooth muscle relaxation and cell division. PDE5 is found in various tissues throughout the body and drugs designed to inhibit the enzyme (and therefore promote cGMP) play important roles in manipulating cardiovascular biology, including enhancing the toxicity of many chemotherapies while also protecting the heart from harm often caused by various forms of chemotherapies.

Regorafenib was approved by the FDA in 2012 for the treatment of metastatic colorectal cancer. In 2013, the FDA expanded its use to treat patients with advanced gastrointestinal stromal tumors. A multi-kinase inhibitor, the drug works by inhibiting multiple proteins involved in cancer, including platelet derived growth factor receptors (PDGFR). PDGFR is a type of protein that regulates cell growth, division and development. In particular, PDGFR plays a significant role in the growth of blood vessels from already-existing blood vessel tissue. This process, called angiogenesis, when uncontrolled is a characteristic of cancer.

While regorafenib has been proven to extend a cancer patient’s life span, it only rarely causes tumors to shrink. “Finding ways to make regorafenib and other similar drugs work better by using them in combination may advance the treatment options for patients with cancer,” says Poklepovic, medical oncologist and member of the Developmental Therapeutics research program at Massey and assistant professor in the Division of Hematology, Oncology and Palliative Care at VCU School of Medicine. “This concept shows that by targeting the pathways cancer cells use to survive, we can potentially find ways to use common medications in combination with chemotherapies to make them more effective.”

Poklepovic hopes that the data collected from this trial and others of its kind will eventually lead to the development of useful anti-tumor therapies to be further tested in patients with solid tumors. Massey scientists are currently leading additional pre-clinical studies on combinations of PDE5 inhibitors and anti-cancer agents as well as another clinical trial (reference No. MCC-14816) for the treatment of brain tumors using sildenafil, valproic acid and sorafenib, a drug similar to regorafenib.

The sildenafil+regorafenib trial is now accepting patients at Massey’s Dalton Oncology Clinic in downtown Richmond. Those interested in enrolling or learning more should contact Massey’s Clinical Trials Office at (804) 628-2364 and reference clinical trial MCC-13-09812.

Massey is currently conducting more than 100 total trials on a variety of cancers. View a complete list of all active clinical trials available at Massey.

Written by: Melissa Mitchell