An internally and externally validated nomogram for predicting the risk of irinotecan-induced severe neutropenia in advanced colorectal cancer patients View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-04-16

AUTHORS

W Ichikawa, K Uehara, K Minamimura, C Tanaka, Y Takii, H Miyauchi, S Sadahiro, K Fujita, T Moriwaki, M Nakamura, T Takahashi, A Tsuji, K Shinozaki, S Morita, Y Ando, Y Okutani, M Sugihara, T Sugiyama, Y Ohashi, Y Sakata

ABSTRACT

Background:In Asians, the risk of irinotecan-induced severe toxicities is related in part to UGT1A1*6 (UGT, UDP glucuronosyltransferase) and UGT1A1*28, variant alleles that reduce the elimination of SN-38, the active metabolite of irinotecan. We prospectively studied the relation between the UGT1A1 genotype and the safety of irinotecan-based regimens in Japanese patients with advanced colorectal cancer, and then constructed a nomogram for predicting the risk of severe neutropenia in the first treatment cycle.Methods:Safety data were obtained from 1312 patients monitored during the first 3 cycles of irinotecan-based regimen in a prospective observational study. In development of the nomogram, multivariable logistic regression analysis was used to test the associations of candidate factors to severe neutropenia in the first cycle. The final nomogram based on the results of multivariable analysis was constructed and validated internally using a bootstrapping technique and externally in an independent data set (n=350).Results:The UGT1A1 genotype was confirmed to be associated with increased risks of irinotecan-induced grade 3 or 4 neutropenia and diarrhoea. The final nomogram included type of regimen, administered dose of irinotecan, gender, age, UGT1A1 genotype, Eastern Cooperative Oncology Group performance status, pre-treatment absolute neutrophil count, and total bilirubin level. The model was validated both internally (bootstrap-adjusted concordance index, 0.69) and externally (concordance index, 0.70).Conclusions:Our nomogram can be used before treatment to accurately predict the probability of irinotecan-induced severe neutropenia in the first cycle of therapy. Additional studies should evaluate the effect of nomogram-guided dosing on efficacy in patients receiving irinotecan. More... »

PAGES

1709-1716

Journal

TITLE

British Journal of Cancer

ISSUE

10

VOLUME

112

Author Affiliations

  • Division of Medical Oncology, Department of Medicine, Showa University, School of Medicine, 1-5-8 Hatanodai, 142-8555, Shinagawa-ku, Tokyo, Japan
  • Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, 466-8560, Showa-ku, Nagoya, Japan
  • Department of Surgery, Mitsui Memorial Hospital, Kanda-Izumi-cho 1, 101-8643, Chiyoda-ku, Tokyo, Japan
  • Department of Surgery, Gifu Prefectural General Medical Centre, 4-6-1 Noishiki, 500-8717, Gifu, Japan
  • Department of Surgery, Niigata Cancer Centre Hospital, 2-15-3 Kawagishi-cho, 951-8566, Chuo-ku, Niigata, Japan
  • Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, 260-8670, Chuo-ku, Chiba, Japan
  • Department of Surgery, Tokai University, 143 Shimoyasuya, 259-1193, Isehara, Japan
  • Institute of Molecular Oncology, Showa University, 1-5-8 Hatanodai, 142-8555, Shinagawa-ku, Tokyo, Japan
  • Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Japan
  • Comprehensive Cancer Centre, Aizawa Hospital, 2-5-1 Honjo, 390-8510, Matsumoto, Japan
  • Department of Medical Oncology, Kobe City Medical Centre General Hospital, 2-1-1 Minatojimaminamimachi, 650-0047, Chuo-ku, Kobe, Japan
  • Division of Clinical Oncology, Hiroshima Prefectural Hospital, 1-5-54 Ujina-Kanda, 734-8530, Minami-ku, Hiroshima, Japan
  • Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, 606-8501, Sakyo-ku, Kyoto, Japan
  • Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, 65 Tsurumai-cho, 466-8560, Showa-ku, Nagoya, Japan
  • Medical Affairs Department, Daiichi Sankyo, 3-5-1 Nihonbashi-Honcho, 103-8426, Chuo-ku, Tokyo, Japan
  • Clinical Data & Biostatistics Department, Daiichi Sankyo, 1-2-58 Hiromachi, 140-8710, Shinagawa-ku, Tokyo, Japan
  • Department of Obstetrics and Gynaecology, Iwate Medical University School of Medicine, 19-1 Uchimaru, 020-8505, Morioka, Japan
  • Department of Integrated Science and Engineering for Sustainable Society, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, 112-8551, Tokyo, Japan
  • CEO, Misawa City Hospital, 164-65, Aza Horiguchi, Oaza Misawa, 033-0022, Misawa, Aomori, Japan
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/bjc.2015.122

    DOI

    http://dx.doi.org/10.1038/bjc.2015.122

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1014636188

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25880011


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