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Friday, October 9, 2020

Combination Therapy With Vitamin A Safe for Patients With Pancreatic Cancer

A treatment combination involving the addition of a form of vitamin A to the current standard treatment regimen for pancreatic cancer is safe for patients, according to an early-phase clinical trial led by researchers at Queen Mary University of London.

Following the encouraging results of this phase I trial (STARPAC), published in Nature Communications (2020; doi: 10.1038/s41467-020-18636-w), a second clinical trial called STARPAC2 will now investigate whether the addition of this form of vitamin A, called ATRA, to standard chemotherapy can enhance the efficacy of treatment in patients with pancreatic cancer.

Chemotherapy and radiotherapy alone are relatively unsuccessful in treating pancreatic cancer, and while surgery to remove the tumor offers the best chance of survival, a lack of symptoms in the early stages of the disease means most patients are diagnosed when the cancer is advanced. A novel approach that is able to target the cancer more effectively is urgently required.

Fighting Cancer With Vitamin A

STARPAC was launched following research conducted in the Kocher laboratory at the University of London, which found that using ATRA to treat a particular type of cell, known as stellate cells, within pancreatic tumors restricted tumor growth. Stellate cells have an important role in normal tissue formation; however, they become corrupted in cancer and help to form an impenetrable barrier, known as the stroma, around the pancreatic tumor.

Treating stellate cells with ATRA (a pre-existing drug used for the treatment of acne and some types of leukemia) was found to restore the vitamin A content of the cells, converting them from tumor-promoting cells to cells which have an anti-cancer effect. By combining this drug with chemotherapy in preclinical models, the team were able to disrupt the communication between the cancer cells and the surrounding stromal cells, leading to a reduction in cancer cell proliferation and invasion.

Trial to Determine Safety

To determine the safety of this treatment combination in the clinic, patients were recruited to the phase I STARPAC trial from Barts Health NHS Trust, Imperial College Healthcare NHS Trust, Guys and St Thomas' NHS Foundation Trust, and Cambridge University Hospitals NHS Foundation Trust.

The trial showed that the addition of ATRA to standard chemotherapy had no additional harmful effects in patients when compared with the standard chemotherapy alone, and also demonstrated that the combination does seem to modify the pancreatic cancer stroma in patients.

"It is pleasing to demonstrate that changes in the stroma (or scar tissue) surrounding cancer can be used to potentially change pancreatic cancer behavior," noted Hemant Kocher, MBBS, MS, MD, FRCS, Professor of Liver and Pancreas Surgery at Queen Mary's Barts Cancer Institute (BCI) and Consultant Liver and Pancreas Surgeon at Barts Health NHS Trust. "This proof-of-principle that the stroma can be targeted in patients is a novel and exciting discovery, and this approach may also be able to be applied to other cancers and diseases where the stroma performs a critical role in disease progression."

Following on from STARPAC, a phase II clinical trial will set out to determine whether the addition of ATRA to current standard chemotherapy can improve the treatment outcome in pancreatic cancer. Led by Kocher, the team hopes the STARPAC2 trial could lead to the realization of a vital new treatment option for patients with pancreatic cancer, and hopefully, for some patients this combination will shrink the tumor to the point where surgery to remove the remaining tumor is possible.