Author/Editor		Niraula, Saroj; Šeruga, Boštjan; Ocaña, Alberto; Shao, Tiffany; Goldstein, Robyn; Tannock, Ian; Amir, Eitan
Title		The price we pay for progress
Type		članek
Vol. and No.		Letnik 30, št. 24
Publication year		2012
Volume		str. 3012-3019
ISSN		0732-183X - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Language		eng
Abstract		Registration of new anticancer drugs is usually based on results of randomized controlled trials (RCTs) showing improved efficacy when compared with standard therapy. There is relatively less emphasis on toxicity. In our study, we analyze serious toxicities of newly approved anticancer drugs reported in pivotal RCTs used for drug registration. We identified RCTs evaluating agents for the treatment of solid tumors approved by the US Food and Drug Administration between 2000 and 2010. Odds ratios (OR) and 95% CI were computed for three end points of safety and tolerability treatment-related death, treatment-discontinuation related to toxicity, and grade 3 or 4 adverseevents (AEs). These were then pooled in a meta-analysis. Correlations between these end points and the hayard ratios for overall survival (OS) and progression-free survival (PFS) were also assessed. Thirty-eight RCTs were analyzed. Compared with control groups, the odds of toxic death was greater for new agents (OR, 1.40, 95% CI, 1.15 to 1.70, P < .001) as were the odds of treatment-discontinuation (OR, 1.33, 95% CI, 1.22 to 1.45, P < .001). Grade 3 or 4 AEs (OR, 1.52, 95% CI, 1.35 to 1. 71, P < .001) were also more common with new agents, especially nonhematologic AEs such as diarrhea, skin reactions, and neuropathy. There were no significant correlations between safety end points and OS or PFS. New anticancer agents that lead to improvements in time-to-event end points also increase morbidity and treatment-related mortality. The balance between efficacy and toxicity may be less favorable in clinical practice because of selection of fewer patients with good performance status and limited comorbidities. Patients baseline health characteristics should be considered when choosing therapy.
Descriptors		Neoplasms Antineoplastic agents Meta-analysis Odds ratio Survival analysis Drug therapy Adverse effects Toxicity