Comparison of efficacy and safety of first-line palliative chemotherapy with EOX and mDCF regimens in patients with locally advanced inoperable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma: a randomized phase 3 trial

Sebastian Ochenduszko, Miroslawa Puskulluoglu, Kamil Konopka, Kamil Fijorek, Katarzyna Urbanczyk, Andrzej Budzynski, Maciej Matlok, Agata Lazar, Anna Sinczak-Kuta, Michal Pedziwiatr, Krzysztof Krzemieniecki, Sebastian Ochenduszko, Miroslawa Puskulluoglu, Kamil Konopka, Kamil Fijorek, Katarzyna Urbanczyk, Andrzej Budzynski, Maciej Matlok, Agata Lazar, Anna Sinczak-Kuta, Michal Pedziwiatr, Krzysztof Krzemieniecki

Abstract

The aim of the study was to compare efficacy and safety of first-line palliative chemotherapy with (EOX) epirubicin/oxaliplatin/capecitabine and (mDCF) docetaxel/cisplatin/5FU/leucovorin regimens for untreated advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma. Fifty-six patients were randomly assigned to mDCF (docetaxel 40 mg/m(2) day 1, leucovorin 400 mg/m(2) day 1, 5FU 400 mg/m(2) bolus day 1, 5FU 1000 mg/m(2)/d days 1 and 2, cisplatin 40 mg/m(2) day 3) or EOX (epirubicin 50 mg/m(2) day 1, oxaliplatin 130 mg/m(2) day 1, capecitabine 1250 mg/m(2)/d days 1-21). The primary endpoint was overall survival. The median overall survival was 9.5 months with EOX and 11.9 months with mDCF (p = 0.135), while median progression-free survival was 6.4 and 6.8 months, respectively (p = 0.440). Two-year survival rate was 22.2 % with mDCF compared to 5.2 % with EOX. Patients in the EOX arm had more frequent reductions in chemotherapy doses (34.5 vs. 3.7 %; p = 0.010) and delays in subsequent chemotherapy cycles (82.8 vs. 63.0 %; p = 0.171). There was no statistically significant difference in the rates of grade 3-4 adverse events (EOX 79.3 vs. mDCF 61.5 %; p = 0.234). As compared with the mDCF, the EOX regimen was associated with more frequent nausea (34.5 vs. 15.4 %), thromboembolic events (13.8 vs. 7.7 %), abdominal pain (13.8 vs. 7.7 %) and grades 3-4 neutropenia (72.4 vs. 50.0 %), but lower incidences of anemia (44.8 vs. 61.5 %), mucositis (6.9 vs. 15.4 %) and peripheral neuropathy (6.9 vs. 15.4 %). In conclusion, the mDCF regimen was associated with a statistically nonsignificant 2.4-month longer median overall survival without an increase in toxicity. This trial is registered at ClinicalTrials.gov, number NCT02445209.

Keywords: EOX; Gastric cancer; Palliative chemotherapy; Safety; Toxicity; mDCF.

Figures

Fig. 1
Fig. 1
CONSORT diagram depicting the trajectory of the trial
Fig. 2
Fig. 2
Kaplan–Meier estimates of a overall and b progression-free survival

References

    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi: 10.3322/caac.20107.
    1. Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA, Rausch M. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 1993;72:37–41. doi: 10.1002/1097-0142(19930701)72:1<37::AID-CNCR2820720109>;2-P.
    1. Pyrhönen S, Kuitunen T, Nyandoto P, Kouri M. Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer. 1995;71:58–91. doi: 10.1038/bjc.1995.114.
    1. Glimelius B, Ekstrom K, Hoffman K, Graf W, Sjödén PO, Haglund U, et al. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol. 1997;8:163–168. doi: 10.1023/A:1008243606668.
    1. Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006;24:2903–2909. doi: 10.1200/JCO.2005.05.0245.
    1. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36–46. doi: 10.1056/NEJMoa073149.
    1. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 study group. J Clin Oncol. 2006;24:4991–4997. doi: 10.1200/JCO.2006.06.8429.
    1. Shah MA, Shibata S, Stoller R, Kemeny M, Ritch PS, Krishnamurthiet SS, et al. Random assignment multicenter phase II study of modified docetaxel, cisplatin, fluorouracil (mDCF) versus DCF with growth factor support (GCSF) in metastatic gastroesophageal adenocarcinoma (GE). J Clin Oncol. 2010;28:15s,(suppl; abstr 4014).
    1. Andreyev HJ, Norman AR, Oates J, Cunningham D. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies? Eur J Cancer. 1998;34:503–509. doi: 10.1016/S0959-8049(97)10090-9.
    1. Chau I, Norman AR, Cunningham D, Waters JS, Oates J, Ross PJ. Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer: pooled analysis from three multicenter, randomized, controlled trials using individual patient data. J Clin Oncol. 2004;22:2395–2403. doi: 10.1200/JCO.2004.08.154.
    1. Chau I, Ashley S, Cunningham D. Validation of the royal marsden hospital prognostic index in advanced esophagogastric cancer using individual patient data from the REAL 2. J Clin Oncol. 2009
    1. Geynisman DM. Adherence to targeted oral anticancer medications. Discov Med. 2013;15:231–241.
    1. Chen XL, Chen XZ, Yang C, Liao YB, Li H, Wang L, et al. Docetaxel, cisplatin and fluorouracil (DCF) regimen compared with non-taxane-containing palliative chemotherapy for gastric carcinoma: a systematic review and meta-analysis. PLoS ONE. 2013
    1. Tetzlaff ED, Correa AM, Komaki R, Swisher SG, Maru D, Ross WA, et al. Significance of thromboembolic phenomena occurring before and during chemoradiotherapy for localized carcinoma of the esophagus and gastroesophageal junction. Dis Esophagus. 2008;21:575–581. doi: 10.1111/j.1442-2050.2008.00829.x.
    1. Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5:632–634. doi: 10.1111/j.1538-7836.2007.02374.x.

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