Reducing Nephrotoxicity in Cancer Patients Undergoing CT

In frail patients with cancer who are to undergo contrast-enhanced CT, the choice of iodated contrast medium can be key to reducing risk for impaired renal function and the development of contrast-induced nephropathy (CIN).

In a head-to-head comparison of two contrast media, iodixanol (Visipaque, GE Healthcare) appeared to have a better safety profile than iopromide (Ultravist, Bayer Healthcare).

The results come from the blinded, randomized COMEDIANS trial, which was conducted in 504 cancer patients at low risk for CIN who underwent chest-abdomen-pelvic CT. The trial was conducted by Maddalena Barba, MD, of the Regina Elena National Cancer Institute in Rome, Italy, and colleagues.

The study was published online August 4 in the Journal of Cellular Physiology.

Currently, there is no evidence to support the use of a specific contrast medium in cancer patients, the study authors note. They point out that CT is one of the imaging techniques most frequently used in cancer management, from diagnosis and disease staging to evaluation of treatment response and follow-up.

Although CIN can be minor ― defined by the study investigators as a 25% increase in serum creatinine level ― more severe cases can lead to renal failure, the need for dialysis, or death. Patients with cancer who are weakened by disease or treatment may be particularly vulnerable.

“It is our responsibility to focus on the safety of fragile patients, such as those affected by cancer,” coauthor Irene Terrenato, PhD, of the Regina Elena National Cancer Institute in Rome, said in a statement. “Iodated contrast media is essential, and, unfortunately, we often observe adverse events on renal function due to contrast media use, such as CIN.”

“To understand which one [contrast medium] minimizes the incidence of CIN is fundamental, and this study arises from the need to protect our patients as much as possible,” added Stefano Canitano, MD, who is also at the Regina Elena National Cancer Institute.

Cancer Patients Develop CIN

The cancer patients taking part in this study were at low risk of developing neuropathy. At baseline, the patients’ estimated glomerular filtration rate (eGFR) was >60 mL/min.

The researchers report that CIN developed at 24 hours in seven patients in the iopromide group compared to two patients in the iodixanol group (= 0.34).

The same trend was seen with late-occurrence events, with eight patients in the iopromide group developing CIN at 72 hours compared to two in the iodixanol group (= .11).

Overall, 17 patients developed CIN. Among those patients, the event rate was higher in the iopromide arm (= .045), although no cases of permanent CIN or significant differences in adverse events or GFR were observed.

“The distribution of CIN events across the study arms seemed to provide a suggestion in support of the use of iodixanol in light of the more favourable toxicity profile,” the study authors say. “However,” they add, “none of these results reached the predefined cut off for statistical significance.” These findings need to be confirmed and the underlying biological mechanisms clarified in larger trials with a similar design, they emphasize.

“Our results can represent a first indication for radiologists who are responsible for performing CT scans on very compromised patients daily,” commented coauthor Antonio Giordano, MD, PhD, from the University of Siena and Istituto Toscano Tumori, in Siena, Italy, who is also the president of the Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, in Philadelphia, Pennsylvania.

He emphasized that “further studies are strongly recommended to confirm these results.”

Specifically, biomarkers associated with increased risk for CIN need to be identified, Dr Giordano told Medscape Medical News. He noted that “sera from the participants in the COMEDIANS trial are stored at our biorepository.”

Importantly, these results are consistent with those from previously published randomized controlled trials demonstrating less patient discomfort, lower frequency of adverse events, and equivalent or higher CT image quality with iodixanol compared with low-osmolar contrast media, Dr Giordano said.

Study Details

The study enrolled patients from four cancer enters who were to undergo a chest-abdomen-pelvis CT with iodated contrast media. A total of 247 patients were centrally randomly allocated to receive iodixanol; 250 patients received iopromide. Although patients and nurses were blinded to group assignment, the pharmacologist, radiologists, technicians, and statisticians were not.

CIN was defined as a decrease of baseline eGFR of >25%. Serum creatinine was used to assess CIN development in addition to eGFR.

The study design, with its focus on cancer patients at very low risk of developing CIN, “renders our findings worthy of attention,” the study authors say. Previous studies have been largely observational and have varied in size, design, and patient characteristics, they note.

Limitations of the study include its low power and failure to reach the recruitment target of 2868 patients, the study authors acknowledge.

This study was funded by the Italian Agency of Drugs. GE Healthcare provided educational support to the biostatistical and methodologic core of the research group.

Original Medscape Post          PubMed Abstract