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

• Published in: Annals of oncology Vol. 23; no. 8; pp. 1963 - 1967
• Main Authors: Wheler, J.J., Tsimberidou, A.M., Hong, D.S., Naing, A., Falchook, G.S., Fu, S., Moulder, S., Stephen, B., Wen, S., Kurzrock, R.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-08-2012; Oxford University Press
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents - adverse effects; Biological and medical sciences; chemotherapeutics; Child; Child, Preschool; Clinical Trials, Phase I as Topic; Female; Humans; Male; Medical sciences; Middle Aged; Molecular Targeted Therapy - adverse effects; Neoplasms - drug therapy; Original; Pharmacology. Drug treatments; phase I; predictive factors; Retrospective Studies; targeted therapies; toxicity; Young Adult; toxicity; phase I; targeted therapies; chemotherapeutics; predictive factors; Antineoplastic agent; Human; Targeted therapy; Toxicity; Patient; Malignant tumor; Chemotherapy; Treatment; Targeted drug; Risk factor; Phase I trial; Predictive factor; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mds027

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