PMID- 22802313
OWN - NLM
STAT- MEDLINE
DCOM- 20121030
LR  - 20220311
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 30
IP  - 24
DP  - 2012 Aug 20
TI  - The price we pay for progress: a meta-analysis of harms of newly approved 
      anticancer drugs.
PG  - 3012-9
LID - 10.1200/JCO.2011.40.3824 [doi]
AB  - PURPOSE: 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. PATIENTS AND METHODS: 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 adverse 
      events (AEs). These were then pooled in a meta-analysis. Correlations between 
      these end points and the hazard ratios for overall survival (OS) and 
      progression-free survival (PFS) were also assessed. RESULTS: 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. CONCLUSION: 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.
FAU - Niraula, Saroj
AU  - Niraula S
AD  - Princess Margaret Hospital, Toronto, ON, Canada.
FAU - Seruga, Bostjan
AU  - Seruga B
FAU - Ocana, Alberto
AU  - Ocana A
FAU - Shao, Tiffany
AU  - Shao T
FAU - Goldstein, Robyn
AU  - Goldstein R
FAU - Tannock, Ian F
AU  - Tannock IF
FAU - Amir, Eitan
AU  - Amir E
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20120716
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Drugs, Investigational)
SB  - IM
CIN - Nat Rev Clin Oncol. 2012 Sep;9(9):488. PMID: 22850750
MH  - Antineoplastic Agents/*adverse effects
MH  - *Drug Approval
MH  - Drugs, Investigational/*adverse effects
MH  - Female
MH  - Humans
MH  - Male
MH  - Neoplasms/*drug therapy/*mortality
MH  - *Randomized Controlled Trials as Topic
MH  - Withholding Treatment
EDAT- 2012/07/18 06:00
MHDA- 2012/10/31 06:00
CRDT- 2012/07/18 06:00
PHST- 2012/07/18 06:00 [entrez]
PHST- 2012/07/18 06:00 [pubmed]
PHST- 2012/10/31 06:00 [medline]
AID - JCO.2011.40.3824 [pii]
AID - 10.1200/JCO.2011.40.3824 [doi]
PST - ppublish
SO  - J Clin Oncol. 2012 Aug 20;30(24):3012-9. doi: 10.1200/JCO.2011.40.3824. Epub 2012 
      Jul 16.