A prospective monitoring of fatal serious adverse events (SAEs) in a Dutch Colorectal Cancer Group (DCCG) phase III trial (CAIRO) in patients with advanced colorectal cancer.
BACKGROUND
Early and correct assessment of treatment-related mortality is highly important in clinical cancer trials. However, no data are available on the quality of safety monitoring.


METHODS
An on-site review was carried out by the study coordinators of the individual charts of all patients participating in the Capecitabine-Irinotecan-Oxaliplatin (CAIRO) study who had died within 30 days of the last administration of study drugs when death was accompanied by any other event than disease progression. The relationship between treatment and death was categorized as unrelated, remote, possible, or probable and submitted to an independent data monitoring committee (IDMC). These results were then compared with the initial assessment of the local investigator.


RESULTS
Forty of 820 patients qualified for review. The relationship between cause of death and study drugs was changed in 26 patients (65%). A major protocol violation (MPV) was identified in 12 of 14 patients with a probable relationship between cause of death and study treatment.


CONCLUSIONS
There was little agreement between the relation as assessed by the local investigator compared with the IDMC. A quality control improves the assessment of safety results and the observed MPVs underscore the importance of educating medical staff and patients.
Mol
L
L
Trails Office, Comprehensive Cancer Centre East (IKO), Nijmegen.
Koopman
M
M
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Ottevanger
P B
PB
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Punt
C J A
CJA
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Electronic address: C.Punt@onco.umcn.nl.
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000069287:Capecitabine; D002423:Cause of Death; D017326:Clinical Trials, Phase III as Topic / Q000941:ethics / Q000706:statistics & numerical data; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018450:Disease Progression; D016903:Drug Monitoring; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000941:ethics / Q000706:statistics & numerical data; D009426:Netherlands / Q000453:epidemiology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D012189:Retrospective Studies
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin