Risk of serious toxicity in 1181 patients treated in phase I clinical trials of predominantly targeted anticancer drugs: the M. D. Anderson Cancer Center experience

Abstract

Background: This study assessed toxicity in advanced cancer patients treated in a phase I clinic that focuses on targeted agents.

Patients and methods: An analysis of database records of 1181 consecutive patients with advanced cancer who were treated in the phase I program starting 1 January 2006 was carried out.

Results: All patients were treated on at least 1 of the 82 phase I clinical trials. Overall, 56 trials (68.3%) had only targeted agents, 13 (15.9%) only cytotoxics, and 13 (15.9%) targeted and cytotoxic agents. Rates of grade 3 and 4 toxicity that were at least possibly drug related were 7.1% and 3.2%, respectively, and 5 of the 1181 patients (0.4%) died from toxicity that was at least possibly drug related. The most common grade 3 or more toxic effects were neutropenia, thrombocytopenia, anemia, dehydration, infection, altered mental status, bleeding, vomiting, nausea, and diarrhea. Eastern Cooperative Oncology Group (ECOG) performance status greater than zero and use of a cytotoxic agent were selected as independent factors associated with serious toxicity.

Conclusion: Phase I trials of primarily targeted agents showed low rates of toxicity, with 10.3% of patients experiencing grade 3 or 4 toxicity and a 0.4% rate of death, at least possibly drug related.

Figure 1

Pie chart showing percentage of patients in each tumor type (total n = 1181). Asterisk indicates that the gastrointestinal tumors include colon (n = 185); pancreas (n = 61); rectum (n = 46); esophagus (n = 26); appendix (n = 18); small intestine (n = 14); gastric (n = 12); hepatocellular (n = 11); cholangiocarcinoma (n = 8); anus (n = 6); peritoneum (n = 2); cholangiocarcinoma and hepatocellular (n = 2); and liver, not otherwise specified (n = 1).