Older drug could have exciting new role in treating colorectal cancer

July 12, 2003

WINSTON-SALEM, N.C. - Researchers at Wake Forest University Baptist Medical Center are reporting how a 15-year-old drug could have a promising new role in the treatment of rectal cancer.

The drug is oxaliplatin, and when administered in combination with fluorouracil (5-FU) plus leucovorin--standard therapy for patients with advanced/metastatic colorectal cancer--it makes the radiation therapy more effective. Oxaliplatin is one in a family of platinum-based drugs, which contain small molecules that interact with DNA and disrupt the replication process. Some cancers, however, have developed resistance to other platinum-based drugs.

"This the first drug to come along in a while that's effective in treating human cancers that are resistant to other platinum-based therapies," said Suzanne M. Hess, Ph.D., associate professor of Radiation Oncology at Wake Forest University School of Medicine, and one of the authors of an abstract presented at the American Association for Cancer Research meeting in Washington, D.C. "One of the other benefits is that it works with a combination of other drugs and doesn't have the associated toxicities."

Oxiliplatin was developed in 1987 and used to treat cancers of the colon and rectum that had already spread to other organs, but the drug had never been fully explored to determine if it would be safe or effective in patients with an earlier stage of the disease. Researchers at Wake Forest tackled that question in the lab, and in 2002 published the first abstract showing that oxaliplatin could safely and dramatically enhance the impact of standard radiation therapy.

After a speedy review in 2002, the Food and Drug Administration approved oxaliplatin (EloxatinTM, manufactured by Sanofi-Synthelabo) in combination with 5-FU and leucovorin for patients with metastatic cancer of the colon or rectum.

"The encouraging pre-clinical studies from Wake Forest, in part, resulted in several cooperative group clinical trials evaluating the combination of oxaliplatin and radiation for patients with rectal cancer," said A. William Blackstock Jr., M.D., assistant professor of radiation oncology and lead author on the abstract presented in Washington. "The clinical trials with oxaliplatin reported thus far make it clear that this drug will soon become an integral part of the treatment of all patients with colorectal cancer."

Blackstock said Wake Forest researchers found that oxaliplatin works quite differently than cisplatin, a related platinum-based drug that has been widely used in cancer treatment for years. The mechanism remains under study, but oxaliplatin has a bulkier diaminocyclohexane (DACH) ligand not present in the structure of cisplatin. This line of research could demonstrate how oxaliplatin can be effective against tumors that are resistant to cisplatin.

In addition to basic research into the mechanism through which oxaliplatin prevents DNA replication in tumor cells, clinical research continues at Wake Forest and elsewhere on the effect and outcomes of using oxaliplatin with radiation in patients with an earlier stage of rectal cancer.

"It's still early, but the studies are showing some activity," Blackstock said. "We treated one patient here at Wake Forest with the combination, and she had a complete response," Blackstock said. "Our laboratory data suggested that we might see significant anti-tumor effects."

According to the American Cancer Society, cancers of the colon and rectum (colorectal) are the third most common site of new cases and deaths among men and women in the United States. An estimated 148,300 new cases and 56,000 deaths are expected this year.
-end-
In addition to Hess, Blackstock's co-authors on the abstract as are Joel Anderson and Rachelle Johnson, research technicians at Wake Forest.

Media Contacts: Karen Richardson, (krchrdsn@wfubmc.edu) or Mark Wright (mwright@wfubmc.edu) at 336-716-4587.

Wake Forest Baptist Medical Center

Related Clinical Trials Articles from Brightsurf:

Nearly 1 in 5 cancer patients less likely to enroll in clinical trials during pandemic
A significant portion of cancer patients may be less likely to enroll in a clinical trial due to the ongoing coronavirus pandemic.

COVID-19 clinical trials lack diversity
Despite disproportionately higher rates of COVID-19 infection, hospitalization and death among people of color, minority groups are significantly underrepresented in COVID-19 clinical trials.

Why we should trust registered clinical trials
In a time when we have to rely on clinical trials for COVID-19 drugs and vaccines, a new study brings good news about the credibility of registered clinical trials.

Inclusion of children in clinical trials of treatments for COVID-19
This Viewpoint discusses the exclusion of children from coronavirus disease 2019 (COVID-19) clinical trials and why that could harm treatment options for children.

Review evaluates how AI could boost the success of clinical trials
In a review publishing July 17, 2019 in the journal Trends in Pharmacological Sciences, researchers examined how artificial intelligence (AI) could affect drug development in the coming decade.

Kidney patients are neglected in clinical trials
The exclusion of patients with kidney diseases from clinical trials remains an unsolved problem that hinders optimal care of these patients.

Clinical trials beginning for possible preeclampsia treatment
For over 20 years, a team of researchers at Lund University has worked on developing a drug against preeclampsia -- a serious disorder which annually affects around 9 million pregnant women worldwide and is one of the main causes of death in both mothers and unborn babies.

Underenrollment in clinical trials: Patients not the problem
The authors of the study published this month in the Journal of Clinical Oncology investigated why many cancer clinical trials fail to enroll enough patients.

When designing clinical trials for huntington's disease, first ask the experts
Progress in understanding the genetic mutation responsible for Huntington's disease (HD) and at least some molecular underpinnings of the disease has resulted in a new era of clinical testing of potential treatments.

New ALS therapy in clinical trials
New research led by Washington University School of Medicine in St.

Read More: Clinical Trials News and Clinical Trials Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.