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St. Jude investigators have found a way to administer high doses of the potentially life-saving anticancer drug irinotecan to children without causing severe diarrhea. A report on this study appears in the February 1 issue of the Journal of Clinical Oncology.
Irinotecan was previously given only intravenously, but St. Jude clinicians sought to give it orally to children with tumors of the brain and other areas of the body. This prevents the need for repeatedly inserting intravenous needles in children for each treatment.
Another advantage to oral administration is that the drug is given in an inactive form that must be converted by the body into an active form, according to Wayne Furman, MD, Hematology-Oncology, the paper’s first author. Since this conversion occurs in the digestive tract, irinotecan treatment is more efficient when the drug is given by mouth. Whether irinotecan is given orally or intravenously, it is metabolized and excreted by the liver into the gastrointestinal tract. Scientists believe that certain bacteria feed on the drug and produce a byproduct that causes severe diarrhea.
The researchers showed that by treating children with the antibiotic cefixime beginning five days before giving the patients oral doses of the irinotecan, they could give higher oral doses while minimizing the side effect, apparently because the antibiotic kills the troublemaking bacteria, Furman said.
“The success of this initial study suggests that we should incorporate oral cefixime in the treatment of children receiving irinotecan to allow us to increase the therapeutic value of irinotecan,” said the paper’s senior author, Victor Santana, MD, Hematology-Oncology.
Other St. Jude authors of the paper include Catherine Billups and Jianrong Wu, PhD, Biostatistics; Najat Daw, MD, Jeffrey Dome, MD, Amar Gajjar, MD, and Carlos Rodriguez-Galindo, MD, all of Hematology-Oncology; and Peter Houghton, PhD, Molecular Pharmacology; and Kristine Crews, PharmD, John Panetta, PhD, and Clinton Stewart, PharmD, all of Pharmaceutical Sciences.
Last update: April 2006