Advertisement

Uracil-Tegafur and Oral Leucovorin Combined With Bevacizumab in Elderly Patients (Aged ≥ 75 Years) With Metastatic Colorectal Cancer: A Multicenter, Phase II Trial (Joint Study of Bevacizumab, Oral Leucovorin, and Uracil-Tegafur in Elderly Patients [J-BLUE] Study)

Published:December 16, 2015DOI:https://doi.org/10.1016/j.clcc.2015.12.001

      Abstract

      Background

      We previously reported that uracil-tegafur with oral leucovorin (UFT/LV) treatment for elderly patients (aged ≥ 75 years) was well-tolerated in a phase II study. In the present study, the efficacy and safety of a modified (1-week shorter administration period) UFT/LV schedule combined with bevacizumab for a similar population are reported.

      Patients and Methods

      The present study was a single-arm, open-label, multicenter, cooperative group clinical trial. The key eligibility criteria included age ≥ 75 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ function. Patients received UFT 300 mg/m2/d and LV 75 mg/d on days 1 to 21 and intravenous bevacizumab 5 mg/kg on days 1 and 15. Treatment was repeated every 28 days. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), overall survival (OS), and safety.

      Results

      Of the 55 patients enrolled from 15 Japanese institutions, 52 eligible patients were evaluated. Their median age was 80 years (range, 75-87 years), and 73% had an ECOG performance status of 0. The median PFS was 8.2 months (95% confidence interval [CI], 6.2-10 months). The ORR was 40% (95% CI, 27%-55%). The median OS was 23 months (95% CI, 12-33 months). The most common grade 3 and 4 treatment-related adverse events were hypertension (12%), fatigue (8%), anemia (8%), nausea (6%), and diarrhea (6%). Treatment-related death occurred in 2 patients.

      Conclusion

      UFT/LV (3 weeks of therapy and 1 week without) combined with biweekly bevacizumab is a tolerable and effective treatment option for elderly patients (aged ≥ 75 years) with metastatic colorectal cancer.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Colorectal Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Scheithauer W.
        • Rosen H.
        • Kornek G.V.
        • et al.
        Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.
        BMJ. 1993; 306: 752-755
        • Saltz L.B.
        • Clarke S.
        • Diaz-Rubio E.
        • et al.
        Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study.
        J Clin Oncol. 2008; 26: 2013-2019
        • Douillard J.Y.
        • Siena S.
        • Cassidy J.
        • et al.
        Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study.
        J Clin Oncol. 2010; 28: 4697-4705
        • Van Cutsem E.
        • Kohne C.H.
        • Lang I.
        • et al.
        Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status.
        J Clin Oncol. 2011; 29: 2011-2019
        • Maughan T.S.
        • Adams R.A.
        • Smith C.G.
        • et al.
        Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial.
        Lancet. 2011; 377: 2103-2114
        • Bokemeyer C.
        • Bondarenko I.
        • Hartmann J.T.
        • et al.
        Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study.
        Ann Oncol. 2011; 22: 1535-1546
        • Falcone A.
        • Ricci S.
        • Brunetti I.
        • et al.
        Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest.
        J Clin Oncol. 2007; 25: 1670-1676
        • Douillard J.Y.
        • Hoff P.M.
        • Skillings J.R.
        • et al.
        Multicenter phase III study of uracil/tegafur and oral leucovorin versus fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer.
        J Clin Oncol. 2002; 20: 3605-3616
        • Carmichael J.
        • Popiela T.
        • Radstone D.
        • et al.
        Randomized comparative study of tegafur/uracil and oral leucovorin versus parental fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer.
        J Clin Oncol. 2002; 20: 3617-3627
        • Hochster H.S.
        • Luo W.
        • Elizabeta C.
        • et al.
        Phase II study of uracil-tegafur with leucovorin in elderly (≥ 75 years old) patients with colorectal cancer: ECOG 1299.
        J Clin Oncol. 2007; 25: 3523-3529
        • Matsumoto T.
        • Nishina T.
        • Mizuta M.
        • et al.
        Phase II study of first-line chemotherapy with uracil-tegafur plus oral leucovorin in elderly (≥ 75 years) Japanese patients with metastatic colorectal cancer: SGOSG-CR0501 study.
        Int J Clin Oncol. 2015; 20: 111-116
        • Kabbinavar F.
        • Hurwitz H.I.
        • Fehrenbacher L.
        • et al.
        Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer.
        J Clin Oncol. 2003; 21: 60-65
        • Kabbinavar F.F.
        • Schulz J.
        • McCleod M.
        • et al.
        Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial.
        J Clin Oncol. 2005; 23: 3697-3705
        • Cunningham D.
        • Lang I.
        • Marcuello E.
        • et al.
        Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial.
        Lancet Oncol. 2013; 14: 1077-1085
        • Koopman M.
        • Antonini N.F.
        • Douma J.
        • et al.
        Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial.
        Lancet. 2007; 370: 135-142
        • Seymour M.T.
        • Maughan T.S.
        • Ledermann J.A.
        • et al.
        Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial.
        Lancet. 2007; 370: 143-152
        • Fuchs C.S.
        • Marshall J.
        • Barrueco J.
        • et al.
        Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: updated results from the BICC-C study.
        J Clin Oncol. 2008; 26: 689-690
        • Tebbutt N.C.
        • Wilson K.
        • Gebski V.J.
        • et al.
        Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group randomized phase III MAX study.
        J Clin Oncol. 2010; 28: 3191-3198
        • Cassidy J.
        • Saltz L.B.
        • Giantonio B.J.
        • et al.
        Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies.
        J Cancer Res Clin Oncol. 2010; 136: 737-743
        • Shirao K.
        • Hoff P.M.
        • Ohtsu A.
        • et al.
        Comparison of the efficacy, toxicity, and pharmacokinetics of a uracil/tegafur (UFT) plus oral leucovorin (LV) regimen between Japanese and American patients with advanced colorectal cancer: joint United States and Japan study of UFT/LV.
        J Clin Oncol. 2004; 22: 3466-3474