Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Clinical Study Chemotherapy 2012;58:419–425 DOI: 10.1159/000345617 Risk Factors for Predicting Severe Neutropenia Induced by Amrubicin in Patients with Advanced Lung Cancer Hiroyuki Watanabe a Hiroaki Ikesue a Marina Oshiro c Kenichiro Nagata a Kazuto Mishima a Atsushi Takada a Kimitaka Suetsugu a Masanori Sueyasu a Nobuaki Egashira a Taishi Harada b Koichi Takayama b Yoichi Nakanishi b Ryozo Oishi a a Department of Pharmacy, Kyushu University Hospital, and b Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, and c Department of Pharmacy, Tomishiro Central Hospital, Okinawa, Japan ated with severe neutropenia induced by AMR. Conclusion: The present results suggest that female gender, higher dos- es of AMR, and lower baseline hematocrit values are predic- tive factors associated with severe neutropenia induced by AMR in patients with advanced lung cancer. Patients who have these predictive factors should be monitored carefully and considered for early granulocyte colony-stimulating fac- tor support. Copyright © 2013 S. Karger AG, Basel Introduction Amrubicin (AMR), an anthracycline, has been widely used in the treatment of small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) in Japan. AMR is mainly metabolized to amrubicinol (AMR-OH) by car- bonyl reductase, and both compounds have an inhibitory effect on DNA topoisomerase II [1]. The in vitro cyto- toxic activity of AMR-OH is approximately 10–100 times more potent than that of AMR [2]. AMR and AMR-OH are inactivated mainly by NAD(P)H (quinone oxide re- Key Words Lung cancer  Amrubicin  Neutropenia  Risk factors for complications  Dose  Hematocrit Abstract Background: Neutropenia is one of the most frequent and dose-limiting toxicities in amrubicin (AMR) therapy. Howev- er, the predictive factors for the development of severe neu- tropenia in AMR therapy remain unknown. Methods: The subjects were 61 advanced lung cancer patients treated with AMR monotherapy. All data were retrospectively collected from the electronic medical record system. A stepwise logis- tic regression analysis was performed to identify risk factors for grade 3–4 neutropenia. Results: Of a total 61 patients, 50 were male and 11 were female. The median dose of AMR was 35.0 mg/m 2 . The incidence of grade 3–4 neutropenia during the first course was 62%. In multivariate analysis, female gen- der (OR = 6.68; 95% CI 1.01–134.15; p = 0.049), higher AMR doses (40 mg/m 2 or more) (OR = 5.98; 95% CI 1.77–23.74; p = 0.003), and lower hematocrit values (OR = 2.04 per 5% de- crease; 95% CI 1.04–4.38; p = 0.036) were significantly associ- Received: July 26, 2012 Accepted after revision: November 5, 2012 Published online: January 4, 2013 Hiroaki Ikesue, PhD Department of Pharmacy, Kyushu University Hospital 3-1-1 Maidashi, Higashi-ku, Fukuoka Fukuoka 8128582 (Japan) E-Mail ikesue  @  pharm.med.kyushu-u.ac.jp © 2013 S. Karger AG, Basel 0009–3157/12/0586–0419$38.00/0 Accessible online at: www.karger.com/che