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Sequential treatment with epirubicin, oxaliplatin and 5FU (EOF) followed by docetaxel, oxaliplatin and 5FU (DOF) in patients with advanced gastric or gastroesophageal cancer: a single-institution experience

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Abstract

Purpose

The aim of this study was to evaluate the activity and safety of epirubicin (EPI), oxaliplatin (l-OHP) and 5fluorouracil (5FU) (EOF) followed by docetaxel (D), l-OHP and 5FU (DOF) in patients with advanced gastric or gastroesophageal junction (GEJ) cancer.

Methods

Forty-five patients were enrolled: 26 gastric and 19 GEJ cancer. Median age was 69 years (range 34–83); ECOG performance status was 0–1 in 37 patients. Treatment consisted of EPI 50 mg/m2 combined with l-OHP 130 mg/m2 on day 1 and continuous infusion 5FU 750 mg/m2 days 1–5 (EOF), every 3 weeks for a maximum of 4 cycles. After EOF completion, patients received D 70 mg/m2 combined with l-OHP 130 mg/m2 on day 1 and continuous infusion 5FU 750 mg/m2 days 1–5 (DOF), every 3 weeks for a maximum of 4 cycles.

Results

After sequential EOF/DOF, the overall response rate was 51.1 % (95 % CI 35.7–66.2 %) and 93.3 % of patients were progression free 6 months after the onset of chemotherapy. The median progression-free survival was 9.5 months (95 % CI 8.0–11.9 months), and the median overall survival was 15.8 months (95 % CI 13.6–18.9 months). Grade 3 neutropenia was observed in 15 patients (33.3 %) after sequential EOF/DOF.

Conclusions

The sequential treatment EOF/DOF is feasible in well-selected patients with advanced gastric or GEJ cancer and shows encouraging survival results.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90

    Article  PubMed  Google Scholar 

  2. Buzzoni R, Bajetta E, Di Bartolomeo M, Miceli R, Beretta E, Ferrario E et al (2006) Pathological features as predictors of recurrence after radical resection of gastric cancer. Br J Surg 93:205–209

    Article  CAS  PubMed  Google Scholar 

  3. Field K, Michael M, Leong T (2008) Locally advanced and metastatic gastric cancer: current management and new treatment developments. Drugs 68:299–317

    Article  CAS  PubMed  Google Scholar 

  4. Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J et al (2010) Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 3:CD004064

    PubMed  Google Scholar 

  5. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M et al (2008) S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9:215–221

    Article  CAS  PubMed  Google Scholar 

  6. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742):687–697

    Article  CAS  PubMed  Google Scholar 

  7. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F et al (2008) Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Oxaliplatin and capecitabine for advanced esophagogastric cancer. N Engl J Med 358(1):36–46

    Article  CAS  PubMed  Google Scholar 

  8. Barone C, Corsi DC, Pozzo C, Cassano A, Fontana T, Noviello MR et al (1998) Treatment of patients with advanced gastric carcinoma with a 5-fluorouracil-based or a cisplatin-based regimen: two parallel randomized phase II studies. Cancer 82:1460–1467

    Article  CAS  PubMed  Google Scholar 

  9. Cho YH, Kim SY, Hong Lee M, Yoo MW, Bang HY, Lee KY et al (2012) Comparative analysis of the efficacy and safety of chemotherapy with oxaliplatin plus fluorouracil/leucovorin between elderly patients over 65 years and younger patients with advanced gastric cancer. Gastric Cancer 15(4):389–395

    Article  CAS  PubMed  Google Scholar 

  10. Day RS (1986) Treatment sequencing, asymmetry, and uncertainty: protocol strategies for combination chemotherapy. Cancer Res 46(8):3876–3885

    CAS  PubMed  Google Scholar 

  11. Norton L, Simon R (1977) Tumor size, sensitivity to therapy, and design of treatment schedules. Cancer Treat Rep 61(7):1307–1317

    CAS  PubMed  Google Scholar 

  12. Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS et al (2007) Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol 25(33):5233–5239

    Article  CAS  PubMed  Google Scholar 

  13. Colucci G, Gebbia V, Galetta D, Riccardi F, Cariello S, Gebbia N (1997) Cisplatin and vinorelbine followed by ifosfamide plus epirubicin vs the opposite sequence in advanced unresectable stage III and metastatic stage IV non-small-cell lung cancer: a prospective randomized study of the Southern Italy Oncology Group (GOIM). Br J Cancer 76(11):1509–1517

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Eagan RT, Frytak S, Richardson RL, Creagan ET, Therneau TM, Coles DT et al (1988) A randomized comparative trial of sequential versus alternating cyclophosphamide, doxorubicin, and cisplatin and mitomycin, lomustine, and methotrexate in metastatic non-small-cell lung cancer. J Clin Oncol 6(1):5–8

    CAS  PubMed  Google Scholar 

  15. Ghosn M, Kattan J, Farhat F, Younes F, Nasr F, Moukadem W, Cancer Research Group/Collaborative Group (CRG/CG), Beirut-Lebanon et al (2008) Sequential vinorelbine–capecitabine followed by docetaxel in advanced breast cancer: long-term results of a pilot phase II trial. Cancer Chemother Pharmacol 62(1):11–18

    Article  CAS  PubMed  Google Scholar 

  16. Cascinu S, Graziano F, Barni S, Labianca R, Comella G, Casaretti R et al (2001) A phase II study of sequential chemotherapy with docetaxel after the weekly PELF regimen in advanced gastric cancer. A report from the Italian group for the study of digestive tract cancer. Br J Cancer 84(4):470–474

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216

    Article  CAS  PubMed  Google Scholar 

  18. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10

    Article  CAS  PubMed  Google Scholar 

  19. Marsman WA, Tytgat GN, ten Kate FJ, van Lanschot JJ (2005) Differences and similarities of adenocarcinomas of the esophagus and esophagogastric junction. J Surg Oncol 92(3):160–168

    Article  CAS  PubMed  Google Scholar 

  20. Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J et al (2009) Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol 27(6):851–856

    Article  CAS  PubMed  Google Scholar 

  21. Kim JA, Lee J, Han B, Park SH, Park JO, Park YS, Lim HY, Kang WK (2011) Docetaxel/cisplatin followed by FOLFIRI versus the reverse sequence in metastatic gastric cancer. Cancer Chemother Pharmacol 68(1):177–184

    Article  CAS  PubMed  Google Scholar 

  22. Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH (2012) Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 30(13):1513–1518

    Article  CAS  PubMed  Google Scholar 

  23. Catalano V, Bisonni R, Graziano F, Giordani P, Alessandroni P, Baldelli AM et al (2013) A phase II study of modified FOLFOX as first-line chemotherapy for metastatic gastric cancer in elderly patients with associated diseases. Gastric Cancer 16(3):411–419

    Article  CAS  PubMed  Google Scholar 

  24. Gubanski M, Johnsson A, Fernebro E, Kadar L, Karlberg I, Flygare P et al (2010) Gastric Cancer Taxotere vs. Campto Trial (GATAC) Study Group Randomized phase II study of sequential docetaxel and irinotecan with 5-fluorouracil/folinic acid (leucovorin) in patients with advanced gastric cancer: the GATAC trial. Gastric Cancer 13(3):155–161

    Article  CAS  PubMed  Google Scholar 

  25. Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B et al (2003) The effect of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 21(22):4165–4174

    Article  CAS  PubMed  Google Scholar 

  26. Grossi F, Aita M, Follador A, Defferrari C, Brianti A, Sinaccio G et al (2007) Sequential, alternating, and maintenance/consolidation chemotherapy in advanced non-small cell lung cancer: a review of the literature. Oncologist 12(4):451–464

    Article  CAS  PubMed  Google Scholar 

  27. Trouilloud I, Dupont-Gossard AC, Malka D, Artru P, Gauthier M, Lecomte T et al (2014) Fixed-dose rate gemcitabine alone or alternating with FOLFIRI.3 (irinotecan, leucovorin and fluorouracil) in the first-line treatment of patients with metastatic pancreatic adenocarcinoma: an AGEO randomised phase II study (FIRGEM). Eur J Cancer 50(18):3116–3124

    Article  CAS  PubMed  Google Scholar 

  28. Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR et al (2011) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 29(30):3968–3976

    Article  CAS  PubMed  Google Scholar 

  29. Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C et al (2013) Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol 14(6):481–489

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM et al (2013) Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol 31(31):3935–3943

    Article  CAS  PubMed  Google Scholar 

  31. Petrioli R, Pascucci A, Francini E, Marsili S, Sciandivasci A, Tassi R et al (2008) Neurotoxicity of FOLFOX-4 as adjuvant treatment for patients with colon and gastric cancer: a randomized study of two different schedules of oxaliplatin. Cancer Chemother Pharmacol 61(1):105–111

    Article  CAS  PubMed  Google Scholar 

  32. Ajani JA (1997) Treatment of patients with upper gastrointestinal carcinomas. Semin Oncol 24(6 Suppl 19):S19–S76

    CAS  PubMed  Google Scholar 

  33. Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S et al (2005) Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol 24:5660–5667

    Article  Google Scholar 

  34. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C et al (2006) 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 31:4991–4997

    Article  Google Scholar 

  35. Iwasa S, Goto M, Yasui H, Nishina T, Takahari D, Nakayama N et al (2012) Multicenter feasibility study of combination therapy with fluorouracil, leucovorin and paclitaxel (FLTAX) for peritoneal disseminated gastric cancer with massive ascites or inadequate oral intake. Jpn J Clin Oncol 42(9):787–793

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the following members of the Multidisciplinary Oncology Group in Gastrointestinal Tumors for their participation in the study: Dr. F. Papi, Dr. A. Bernini, Dr.ssa S. Civitelli, Dr. Calomino, Clinical Surgery; Dr. Vinno savelli, General Surgery; Siena University; Dr. T Cerri Vestri, Arezzo Hospital, Dr. G. Giusti, USL 10, Pisa, Italy.

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Authors and Affiliations

  1. Medical Oncology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Viale Bracci, 53100, Siena, Italy

    Roberto Petrioli, Letizia Laera, Giulia Rossi & Giandomenico Roviello

  2. Medical Oncology Unit, Policlinico Umberto I Hospital, University of Rome, Rome, Italy

    Edoardo Francini & V. Bianco

  3. Unit of General and Minimally Invasive Surgery, Surgery and Neurosciences, University of Siena, Siena, Italy

    Franco Roviello

  4. Unit of Surgical Oncology, Surgery and Neurosciences, University of Siena, Siena, Italy

    Daniele Marrelli

  5. Pharmacology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy

    Anna Ida Fiaschi

  6. Department of Surgery, Policlinico Umberto I Hospital, University of Rome, Rome, Italy

    S. Brozzetti

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  1. Roberto Petrioli
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Correspondence to Roberto Petrioli.

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Petrioli, R., Francini, E., Roviello, F. et al. Sequential treatment with epirubicin, oxaliplatin and 5FU (EOF) followed by docetaxel, oxaliplatin and 5FU (DOF) in patients with advanced gastric or gastroesophageal cancer: a single-institution experience. Cancer Chemother Pharmacol 75, 941–947 (2015). https://doi.org/10.1007/s00280-015-2715-x

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