Drug induced interstitial lung disease in oncology phase I trials.
Interstitial lung disease is a serious drug-related condition that can cause life threatening organ failure. The incidence and risk factors of drug-induced interstitial lung disease (DILD) are unknown in oncology phase I trials. This study analyzed clinical information from 8906 patients with malignancies who were enrolled in 470 phase I trials sponsored by the Cancer Therapy Evaluation Program, National Cancer Institute, from 1988 to 2014. Logistic and Cox statistical analyses were utilized to determine clinical differences between patients who developed DILD and patients who did not. In this study, the overall incidence rate of patients with pulmonary toxicity was 2.7%. The overall incidence rate for DILD was 0.77%, whereas for grade 3 or 4 DILD it was 0.31%. Median time to occurrence of DILD was 1.4 months. The Cox hazard analysis indicated smaller body surface area and a combination of thoracic radiation with investigational drug regimens were significant risk factors for time to occurrence of interstitial lung disease. Investigators should carefully monitor for DILD in oncology patients enrolled in phase I trials with identified risk factors. A 6-month observation period would be sufficient to detect the onset of most DILD in such patients.
Department of Breast and Medical Oncology, National Cancer Center Hospital, National Cancer Center, Tokyo, Japan.|Office for Advanced Medical Care Evaluation, National Cancer Center, Tokyo, Japan.|Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institute of Health, Rockville, Maryland, USA.
Kan
K
Yonemori
Biostatistics and Bioinformatics Section, Center for Advanced Medicine and Clinical Research, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
Akihiro
A
Hirakawa
Department of Breast and Medical Oncology, National Cancer Center Hospital, National Cancer Center, Tokyo, Japan.
Asuka
A
Kawachi
Biostatistics and Bioinformatics Section, Center for Advanced Medicine and Clinical Research, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
Fumie
F
Kinoshita
Department of Breast and Medical Oncology, National Cancer Center Hospital, National Cancer Center, Tokyo, Japan.
Hitomi
H
Okuma
Department of Breast and Medical Oncology, National Cancer Center Hospital, National Cancer Center, Tokyo, Japan.
Tadaaki
T
Nishikawa
Department of Breast and Medical Oncology, National Cancer Center Hospital, National Cancer Center, Tokyo, Japan.
Kenji
K
Tamura
Department of Breast and Medical Oncology, National Cancer Center Hospital, National Cancer Center, Tokyo, Japan.|Office for Advanced Medical Care Evaluation, National Cancer Center, Tokyo, Japan.
Yasuhiro
Y
Fujiwara
Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institute of Health, Rockville, Maryland, USA.
Naoko
N
Takebe
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D015994:Incidence; D017563:Lung Diseases, Interstitial / Q000453:epidemiology* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D012307:Risk Factors
D000970:Antineoplastic Agents
Drug induced interstitial lung disease; investigational new drug; oncology; phase I trial pulmonary toxicity
Cancer Sci. 2016 Dec;107(12):1830-1836
27685762
J Thorac Oncol. 2010 Feb;5(2):179-84
20101144
BMC Res Notes. 2009 Aug 05;2:157
19656374
Curr Drug Saf. 2014;9(3):220-6
24909577
Clin Cancer Res. 2004 Feb 15;10(4):1212-8
14977817
J Clin Oncol. 2006 Jun 1;24(16):2549-56
16735708
Br J Cancer. 2004 Aug;91 Suppl 2:S18-23
15340374
Am J Respir Crit Care Med. 2008 Jun 15;177(12):1348-57
18337594
Mol Cell Biochem. 2015 Feb;400(1-2):153-62
25404465
Cancer J. 2005 Sep-Oct;11(5):417-24
16259873
Open Respir Med J. 2012;6:63-74
22896776