‘Low’ toxicity for phase I cancer trials

By Lynda Williams, Senior MedWire Reporter

Advanced cancer patients participating in phase I clinical trials at the University of Texas MD Anderson Cancer Center experienced a low rate of toxicity, researchers say.

Just 7.1% and 3.2% of 1181 patients, treated within one or more of 82 trials from 2006 through 2008, experienced grade 3 and grade 4 toxicity possibly linked to treatment, and just 0.4% of patients died from possible drug toxicity, report Jennifer Wheler, from the institution, and co-workers.

"In light of the low toxicity and death rates at least possibly related to treatment, the notion of early clinical trials as being dangerous and the threshold for further requirements aimed at decreasing toxicity needs to be carefully evaluated," the team comments.

"This is especially important to consider because the death rate due to tumor was substantially higher than the death rate that was at least possibly related to drug."

The majority of trials were testing targeted agents (68.3%), 15.9% were testing cytotoxics, and 15.9% a combination of targeted and cytotoxic agents.

The most common grade 3 or more severe toxic effects were neutropenia, thrombocytopenia, anemia, dehydration, infection, altered mental status, bleeding, vomiting, nausea, and diarrhea.

Patients were aged a median of 58 years, 50% were female, and 91% of patients had an Eastern Cooperative Oncology Group performance (ECOG) status of 0 or 1 indicating good physical status or minimal physical restriction.

Analysis showed that grade 3 or 4 toxicity was significantly predicted by an Eastern Cooperative Oncology Group performance status above zero (relative risk [RR]=1.7, 12.2 vs 6.2% for status of <1 vs ≥1), and by receipt of a cytotoxic agent (RR=1.8 versus receipt of targeted agent alone, 14.0 vs 8.6%.

Noting there were no deaths definitely related to treatment, and that possible rate was comparable to previously reported rates, the team comments that "even with relatively nontoxic drugs and cautious dose-escalation schemas, achieving further reductions in death rate that was at least possibly drug related, below 0.5%, may not be a feasible goal."

Wheler et al conclude. "Taken together, these results suggest that phase I trials are a safe option for patients with advanced cancer and good performance status, who have failed conventional therapy."

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