Randomized study comparing full dose monotherapy (S-1 followed by irinotecan) and reduced dose combination therapy (S-1/oxaliplatin followed by S-1/irinotecan) as initial therapy for older patients with metastatic colorectal cancer: NORDIC 9

BMC Cancer

Study Protocol

Åke Berglund¹  Bengt Glimelius¹  Halfdan Sorbye²  Pia Österlund³  Per Pfeiffer⁴  Stine Braendegaard Winther⁴  Camilla Qvortrup⁴ 

[1] Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden;Department of Oncology and Department of Clinical Science, Haukeland University Hospital, Postboks 1400, 5021, Bergen, Norway;Department of Oncology, Helsinki University Central Hospital, PO BOX 100, Stenbäckinkatu 9, FI-00029, Helsinki, Finland;Clinicum, Helsinki University, PO BOX 63, Haartmaninkatu 8, 3th floor, 00014, Helsinki, Finland;Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark;

关键词: Randomized phase II;    Non-intensive;    SOX;    IRIS;    Oral;    Geriatric assessment;    Metastatic colorectal cancer;   

DOI  :  10.1186/s12885-017-3526-8

 received in 2016-08-31, accepted in 2017-08-01,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMetastatic colorectal cancer (mCRC) is a disease of older age, but there is a relative lack of knowledge about effects of chemotherapy in older patients as they are under-represented in clinical trials. Little data can guide whether the strategy in older mCRC patients should be a sequential full-dose monotherapy chemotherapy approach or a dose-reduced combination chemotherapy approach. The oral 5FU prodrug S-1 seems to have less side effects than capecitabine and should be an optimal drug for older patients, but few data are available. Improved geriatric assessments are needed to select which older patients should receive therapy.MethodsThe NORDIC 9 trial is a Nordic multicenter randomized phase II study comparing full dose monotherapy (S-1 30 mg/m2 twice daily days 1–14 every 3 weeks, followed by second line irinotecan 250–350 mg/m2 iv day 1 every 3 weeks or 180–250 mg/m2 iv day 1 every 2 weeks) with reduced dose combination therapy (S-1 20 mg/m2 days 1–14 + oxaliplatin 100 mg/m2 iv day 1 every 3 weeks, followed by second line S-1 20 mg/m2 days 1–14 + irinotecan 180 mg/m2 day 1 every 3 week) for older patients (≥70 years) with mCRC who are not candidates for full-dose standard combination therapy. Additional bevacizumab (7.5 mg/kg) is optional in first-line. Blood samples and tumor tissue will be collected to investigate predictive markers. Geriatric screening tools (G-8, VES-13, Timed-Up-and-Go and Handgrip strength), Charlson Comorbidty Index and quality of life (EORTC QLQ-C30) will be evaluated as predictors of efficacy and toxicity. The target sample size is 150 patients.The primary endpoint is progression-free survival and secondary endpoints are time-to-failure of strategy, overall survival, response rate, toxicity, and correlations between biomarkers, pre-treatment characteristics and geriatric assessments.DiscussionThe study will add knowledge on how to treat older mCRC patients who are not candidates for standard combination therapy. Furthermore it may provide understanding of efficacy and tolerability of chemotherapy in older cancer patients and thus offer a better chance for tailored treatment strategies in these patients.Trial registrationEU Clinical Trial Register, EudraCT no. 2014–000394-39. Registered 05 May 2014.

【 授权许可】

CC BY   
© The Author(s). 2017