A new treatment regimen for patients with metastatic colon cancer appears to offer clinical benefit even when used after multiple other treatments have failed, say research physicians at Georgetown Lombardi Comprehensive Cancer Center, a part of Georgetown University Medical Center.

 

The research team found that combining a PARP (a key part of a cell’s DNA repair apparatus) inhibitor with chemotherapy (temozolomide) offers significant benefit in patients who had no further treatment options.

The researchers, who say the study is small and requires further investigation, presented the data in Chicago at the June 2011 annual meeting of the American Society of Clinical Oncology.

Fighting Cancer Cells

Researchers say the chemotherapy damages cancer cells, such as the one shown above, and the PARP inhibitor prevents the cell from repairing itself.

PARP, short for “poly (ADP-ribose) polymerase” is important for protecting normal cells against DNA damage. But cancer cells become resistant to chemotherapy in part by increasing PARP expression and thus rapidly repairing DNA damage intentionally caused by chemotherapy.

The inhibitor is designed to overcome a cancer cell’s ability to repair the damaged DNA, and have shown promise in both breast and ovarian cancer treatment.

In the GUMC study, doctors administered a potent DNA-damaging chemotherapy, temozolomide, with a PARP inhibitor. The theory is that the PARP inhibitor diminishes the ability of cancer cells to fix the damage that inflicted by the temozolomide.

One-Two Punch

“This is a classic one-two punch: the chemotherapy damages the cancer cells and the PARP inhibitor prevents it from fixing itself, leaving the cell to die,” says lead author Michael Pishvaian, an assistant professor at Georgetown Lombardi.

The study enrolled 49 patients with metastatic disease who were not eligible for surgery and had exhausted all of the standard therapies currently used. Despite having advanced cancer, all study participants were still active at work or home.

Researchers found the drug combination controlled cancer growth for nearly six months in 23 percent of the patients, with two patients having a significant reduction in their tumor burden.

Well Tolerated

“The treatment was extremely well tolerated, so to have a period of six months with no tumor growth, but also no significant side effects was really meaningful for the patients,” Pishvaian explains.

Researchers were also able to collect samples of the patients’ tumors for further molecular analysis.

“By testing tissue samples and identifying their molecular fingerprints, perhaps we can identify which patient subgroups are most likely to respond to this new therapeutic combination,” Pishvaian concludes.

Funding for the study was provided by the Ruesch Center for the Cure of Gastrointestinal Cancers at Georgetown Lombardi Comprehensive Cancer Center.