Skip to main content

Advertisement

SpringerLink
Log in

Docetaxel, cisplatin, and fluorouracil combination in neoadjuvant setting in the treatment of locally advanced gastric adenocarcinoma: Phase II NEOTAX study

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

An Erratum to this article was published on 12 June 2015

Abstract

Purpose

This phase II trial aimed to evaluate the efficacy and safety of docetaxel, cisplatin, and fluorouracil (DCF) combination in neoadjuvant setting in patients with locally advanced gastric adenocarcinoma.

Methods

Fifty-nine patients with resectable or unresectable locally advanced gastric and gastroesophageal cancer were recruited in this multicenter, single-arm, open-label, local clinical phase II study conducted at three centers from Turkey between June 2006 and March 2012. Patients had T3–4 or lymph node-positive disease. After staging with imaging and laparotomy or laparoscopy, they received three cycles of DCF with lenograstim. Imaging studies were repeated after the last two cycles. Patients who underwent surgery were followed up for at least 1 year after the surgery. Toxicity and response were evaluated in accordance with NCI-CTC version3.0 and RECIST 1.0.

Results

At baseline, 66.1 % of patients were considered resectable. In 47 patients evaluable, partial response in 16 (34.0 %), stable disease in 27 (57.5 %), and progressive disease in four (8.5 %) were observed. Forty-six patients underwent surgery. In 38 (64.4 %; 95 % confidence interval (CI) 52.2–76.6 %) out of 59 patients, complete resection (R0) was achieved. Median overall and disease-free survival were 19.1 months (95 % CI 13.5–24.7) and 11.6 months (95 % CI 5.9–17.4), respectively. The most frequent grade 3–4 adverse events were neutropenia (52.5 %), febrile neutropenia (11.9 %), leukopenia (39.0 %), and diarrhea (10.5 %). One patient died from an unknown cause.

Conclusions

Classical DCF triplet with lenograstim showed a good clinical response with acceptable safety profile in the treatment of locally advanced gastric and gastroesophageal cancer with a significant R0 rate and manageable toxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Pisters PWT, Kelsen DP, Tepper JE (2011) Cancer of the stomach. In: DeVita VT, Lawrence TS, Rosenberg SA (eds) DeVita, Hellman, and Rosenberg’s cancer: principles and practice of oncology, 8th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1043–1068

    Google Scholar 

  2. National Comprehensive Cancer Network (NCCN) Panel (2013) NCCN clinical practice guidelines in oncology: gastric cancer (including cancer in the proximal 5 cm of the stomach) version 2. http://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf. Accessed 21 Sep 2013

  3. Sym SJ, Chang HM, Ryu MH, Lee JL, Kim TW, Yook JH, Oh ST, Kim BS, Kang YK (2010) Neoadjuvant docetaxel, capecitabine and cisplatin (DXP) in patients with unresectable locally advanced or metastatic gastric cancer. Ann Surg Oncol 17:1024–1032

    Article  PubMed  Google Scholar 

  4. Biffi R, Fazio N, Luca F, Chiappa A, Andreoni B, Zampino MG, Roth A, Schuller JC, Fiori G, Orsi F, Bonomo G, Crosta C, Huber O (2010) Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally-advanced gastric cancer. World J Gastroenterol 16:868–874

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P (2011) Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29:1715–1721

    Article  CAS  PubMed  Google Scholar 

  6. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355:11–20

    Article  CAS  PubMed  Google Scholar 

  7. Ferri LE, Ades S, Alcindor T, Chasen M, Marcus V, Hickeson M, Artho G, Thirlwell MP (2012) Perioperative docetaxel, cisplatin, and 5-fluorouracil (DCF) for locally advanced esophageal and gastric adenocarcinoma: a multicenter phase II trial. Ann Oncol 23:1512–1517

    Article  CAS  PubMed  Google Scholar 

  8. Van Cutsem E, Moiseyenko VM, Tjulandin S, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA, V325 Study Group (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 24:4991–4997

    Article  PubMed  Google Scholar 

  9. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR, Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358:36–46

    Article  CAS  PubMed  Google Scholar 

  10. Bang Y-J, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK, ToGA Trial Investigators (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 376:687–697

    Article  CAS  PubMed  Google Scholar 

  11. Sobin LH, Wittekind C (eds) (2002) International Union Against Cancer (UICC) TNM classification of malignant tumours, 6th edn. Wiley, New York

    Google Scholar 

  12. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (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 92:205–216

    Article  CAS  PubMed  Google Scholar 

  13. Bottcher K, Stein HJ, Becker K (2000) Stomach carcinoma. In: Roder JD, Stein HJ, Fink F (eds) Therapy of gastro-intestinal tumors. Springer, Berlin, pp 217–241

    Chapter  Google Scholar 

  14. Thuss-Patience PC, Hofheinz RD, Arnold D, Florschütz A, Daum S, Kretzschmar A, Mantovani-Löffler L, Bichev D, Breithaupt K, Kneba M, Schumacher G, Glanemann M, Schlattmann P, Reichardt P, Gahn B (2012) Perioperative chemotherapy with docetaxel, cisplatin and capecitabine (DCX) in gastro-oesophageal adenocarcinoma: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Ann Oncol 23:2827–2834

    Article  CAS  PubMed  Google Scholar 

  15. Homann N, Pauligk C, Luley K, Werner kraus T, Bruch HP, Atmaca A, Noack F, Altmannsberger HM, Jäger E, Al-Batran SE (2012) Pathological complete remission in patients with oesophagogastric cancer receiving preoperative 5-fluorouracil, oxaliplatin and docetaxel. Int J Cancer 130:1706–1713

    Article  CAS  PubMed  Google Scholar 

  16. Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, Haag C, Mauer ME, Hasan B, Welch J, Ott K, Hoelscher A, Schneider PM, Bechstein W, Wilke H, Lutz MP, Nordlinger B, Van Cutsem E, Siewert JR, Schlag PM (2010) Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol 28:5210–5218

    Article  PubMed Central  PubMed  Google Scholar 

  17. Schultheis B, Riebeling J, Allali M, Bergmann U, Kummer G, Sendler U, Tannapfel A, Sendler A, Strumberg D (2010) Neoadjuvant treatment of adenocarcinomas of the gastroesophageal junction and stomach: a feasibility trial combining cisplatin and docetaxel with either 5-fluorouracil or capecitabine. Int J Clin Pharmacol Ther 48:451–452

    Article  CAS  PubMed  Google Scholar 

  18. Sun XC, Lin J, Ju AH (2006) Treatment of Borrmann type IV gastric cancer with a neoadjuvant chemotherapy combination of docetaxel, cisplatin and 5-fluorouracil/leucovorin. J Int Med Res 39:2096–2102

    Article  Google Scholar 

  19. D’Ugo D, Persiani R, Rausei S, Biondi A, Vigorita V, Boccia S, Ricci R (2006) Response to neoadjuvant chemotherapy and effects of tumor regression in gastric cancer. Eur J Surg Oncol 32:1105–1109

    Article  PubMed  Google Scholar 

  20. Kaklamanos IG, Walker GR, Ferry K, Franceschi D, Livingstone AS (2003) Neoadjuvant treatment for resectable cancer of the esophagus and the gastroesophageal junction: a meta-analysis of randomized clinical trials. Ann Surg Oncol 10:754–761

    Article  PubMed  Google Scholar 

  21. Li W, Qin J, Sun YH, Liu TS (2010) Neoadjuvant chemotherapy for advanced gastric cancer: a meta-analysis. World J Gastroenterol 16:5621

    Article  PubMed Central  PubMed  Google Scholar 

  22. Knight G, Earle CC, Cosby R, Coburn N, Youssef Y, Malthaner R, Wong RK, Group Gastrointestinal Cancer Disease Site (2013) Neoadjuvant or adjuvant therapy for resectable gastric cancer: a systematic review and practice guideline for North America. Gastric Cancer 16:28–40

    Article  CAS  PubMed  Google Scholar 

  23. Thuss-Patience PC, Kretzschmar A, Dogan Y, Rothmann F, Blau I, Schwaner I, Breithaupt K, Bichev D, Grothoff M, Grieser C, Reichardt P (2011) Docetaxel and capecitabine for advanced gastric cancer: investigating dose-dependent efficacy in two patient cohorts. Br J Cancer 105:505–512

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

Authors would like to thank to Dr. Semra Yoruk from Sanofi Turkey for her valuable contributions by reviewing the manuscript. Prof. Sule Oktay, MD, PhD and Cagla Ayhan, MD from KAPPA Consultancy Training Research Ltd (Istanbul, Turkey) provided technical support in the manuscript preparation, and Oguz Akbas, MD, Ph.D. and Arzu Calisgan from Monitor Medical Research and Consulting (Istanbul, Turkey) conducted the statistical analyses. Monitor Contract Research Organization (Istanbul, Turkey) was responsible for the conduct of the study operations. This work was fully supported by Sanofi Turkey [DOCET-L-00072].

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Ankara Numune Training and Research Hospital, Ankara, Turkey

    Nuriye Ozdemir, Burak Civelek & Nurullah Zengin

  2. Department of Medical Oncology, Adana Teaching and Research Center, Adana Hospital, Kisla Medical Campus, Baskent University Faculty of Medicine, Kazim Karabekir M. 4227 Sk No: 27, 01120, Yuregir, Adana, Turkey

    Huseyin Abali

  3. Department of Radiology, Ankara Numune Training and Research Hospital, Ankara, Turkey

    Murat Vural

  4. Department of Medical Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Suayib Yalcin

  5. Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkey

    Berna Oksuzoglu

  6. Department of Gastroenterology, Turkiye Yuksek Ihtisas Training and Research Hospital, Ankara, Turkey

    Dilek Oguz

  7. Department of Gastroenterological Surgery, Turkiye Yuksek Ihtisas Training and Research Hospital, Ankara, Turkey

    Birol Bostanci

  8. Department of Medical Oncology, Ankara University Faculty of Medicine, Ankara, Turkey

    Bulent Yalcin

Authors
  1. Nuriye Ozdemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huseyin Abali
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Murat Vural
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Suayib Yalcin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Berna Oksuzoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Burak Civelek
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dilek Oguz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Birol Bostanci
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bulent Yalcin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nurullah Zengin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Huseyin Abali.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Figure 1

Overall survival curves according to age groups based on the median age of 59 years in ITT-population (n = 59) (TIFF 137 kb)

Supplementary Figure 2

Overall survival curves according to operation status in ITT-population (n = 59) (TIFF 133 kb)

Supplementary Figure 3

Overall survival in patients with R0 resection in comparison with all other remaining patients (TIFF 119 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ozdemir, N., Abali, H., Vural, M. et al. Docetaxel, cisplatin, and fluorouracil combination in neoadjuvant setting in the treatment of locally advanced gastric adenocarcinoma: Phase II NEOTAX study. Cancer Chemother Pharmacol 74, 1139–1147 (2014). https://doi.org/10.1007/s00280-014-2586-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-014-2586-6

Keywords

Search

Navigation