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Modified Docetaxel and Cisplatin in Combination with Capecitabine (DCX) as a First-Line Treatment in HER2-Negative Advanced Gastric Cancer

  • Bilici, Ahmet (Department of Medical Oncology, Medical Faculty, Istanbul Medipol University) ;
  • Selcukbiricik, Fatih (Department of Medical Oncology, Sisli Etfal Education and Research Hospital) ;
  • Demir, Nazan (Department of Medical Oncology, Sisli Etfal Education and Research Hospital) ;
  • Ustaalioglu, Bala Basak Oven (Department of Medical Oncology, Haydarpasa Numune Education and Research Hospital) ;
  • Dikilitas, Mustafa (Department of Medical Oncology, Acibadem Maslak Hospital) ;
  • Yildiz, Ozcan (Department of Medical Oncology, Medical Faculty, Istanbul Medipol University)
  • Published : 2014.11.06

Abstract

Background: Docetaxel and cisplatin in combination with fluorouracil (DCF) regimen is accepted to be one of the standard regimens in the treatment of advanced gastric cancer. However, substantial toxicity has limited its use in daily clinical practice. Therefore, modification of DCF regimens, including introduction of capecitabine has been investigated to improve the safety profiles. In the present study, the efficacy and toxicity of a regimen with a modified dose of docetaxel and cisplatin in combination with oral capecitabine (DCX) was evaluated in untreated patients with HER2-negative advanced gastric cancer. Materials and Methods: Fifty-four patients with HER2-negative locally advanced or metastatic gastric cancer were included in this cohort. Patients received docetaxel $60mg/m^2$ plus cisplatin $60mg/m^2$ (day 1) combined with capecitabine $1650mg/m^2$ (days 1-14) every 3 weeks. Treatment response, survival, and toxicity were retrospectively analyzed. Results: The median age was 54 years (range: 24-76). The majority of patients (70%) had metastatic disease, while 11 patients (21%) had recurrent disease and underwent curative gastrectomy, and 5 patients (9%) had locally advanced disease (LAD). The median number of DCX cycles was 4. There were 28 partial responses and 11 complete responses, with an overall response rate of 72%. Curative surgery could be performed in four patients among five with LAD. At the median follow-up of 10 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort of patients were 7.4 and 12.1 months, respectively. Dose modification was done in 12 patients due to toxicity in 8 and noncompliance in 4 patients. The most common hematological toxicity was neutropenia, which occurred at grade 3-4 intensity in 10 of 54 patients (27.7%). Febrile neutropenia was diagnosed only in two cases. Conclusions: DCX regimen offers prominent anti-tumor activity and considered to be effective first-line treatment with manageable toxicity for patients with HER2-negative advanced gastric cancer.

Keywords

References

  1. Alici S, Buyukberber S, Alkis N, et al Anatolian Society of Medical Oncology (2013). Low-dose docetaxel/cisplatinleucovorin and 46 hour infusional fluorouracil in metastatic gastric carcinoma. Asian Pac J Cancer Prev, 14, 423-7. https://doi.org/10.7314/APJCP.2013.14.1.423
  2. Bang YJ, Van Cutsem E, Feyereislova 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, 687-97. https://doi.org/10.1016/S0140-6736(10)61121-X
  3. Crew KD, Neugut AI (2006). Epidemiology of gastric cancer. World J Gastroenterol, 12, 354-62.
  4. Cunningham D, Starling N, Rao S, et al (2008). Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med, 358, 36-46. https://doi.org/10.1056/NEJMoa073149
  5. Eisenhauer EA, Therasse P, Bogaerts J, et al (2009). New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer, 45, 228-47. https://doi.org/10.1016/j.ejca.2008.10.026
  6. Field K, Michael M, Leong T (2008). Locally advanced and metastatic gastric cancer: current management and new treatment developments. Drugs, 68, 299-317. https://doi.org/10.2165/00003495-200868030-00004
  7. Glimelius B, Ekstrom K, Hoffman K, et al (1997). Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol, 8, 163-8. https://doi.org/10.1023/A:1008243606668
  8. Hong YS, Song SY, Lee SI, et al (2004). A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol, 15, 1344-7. https://doi.org/10.1093/annonc/mdh343
  9. Kang YK, Ryu MH, Yoo C, et al (2011). Phase I/II study of a combination of docetaxel, capecitabine, and cisplatin (DXP) as first-line chemotherapy in patients with advanced gastric cancer. Cancer Chemother Pharmacol, 67, 1435-43. https://doi.org/10.1007/s00280-010-1444-4
  10. Kang YK, Kang WK, Shin DB, et al (2009). Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol, 20, 666-73. https://doi.org/10.1093/annonc/mdn717
  11. Kim NK, Park YS, Heo DS, et al (1993). A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer. Cancer, 71, 3813-8. https://doi.org/10.1002/1097-0142(19930615)71:12<3813::AID-CNCR2820711205>3.0.CO;2-5
  12. Koizumi W, Saigenji K, Ujiie S, et al (2003). A pilot phase II study of capecitabine in advanced or recurrent gastric cancer. Oncology, 64, 232-6. https://doi.org/10.1159/000069313
  13. Kos FT, Uncu D, Ozdemir N, et al (2011). Comparison of cisplatin-5-fluorouracil-folinic acid versus modified docetaxel-cisplatin-5-fluorouracil regimens in the first-line treatment of metastatic gastric cancer. Chemotherapy, 57, 230-5. https://doi.org/10.1159/000327840
  14. Lorenzen S, Hentrich M, Haberl C, et al (2007). Split-dose docetaxel, cisplatin and leucovorin/fluorouracil as first-line therapy in advanced gastric cancer and adenocarcinoma of the gastroesophageal junction: results of a phase II trial. Ann Oncol, 18, 1673-9. https://doi.org/10.1093/annonc/mdm269
  15. Okines AF, Norman AR, McCloud P, Kang YK, Cunningham D (2009). Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer. Ann Oncol, 20, 1529-34. https://doi.org/10.1093/annonc/mdp047
  16. Ozdemir NY, Abali H, Oksuzoglu B, et al (2010). The efficacy and safety of reduced-dose docetaxel, cisplatin, and 5-fluorouracil in the first-line treatment of advanced stage gastric adenocarcinoma. Med Oncol, 27, 680-4. https://doi.org/10.1007/s12032-009-9268-y
  17. Polyzos A, Felekouras E, Karatzas T, et al (2012). Modified docetaxel-cisplatin in combination with capecitabine as first-line treatment in metastatic gastric cancer. a phase II study. Anticancer Res, 32, 4151-6.
  18. Pyrhonen S, Kuitunen T, Nyandoto P, Kouri M (1995). 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, 71, 587-91. https://doi.org/10.1038/bjc.1995.114
  19. Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, 2013. CA Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
  20. Sym SJ, Chang HM, Ryu MH, et al (2010). Neoadjuvant docetaxel, capecitabine and cisplatin (DXP) in patients with unresectable locally advanced or metastatic gastric cancer. Ann Surg Oncol, 17, 1024-32. https://doi.org/10.1245/s10434-009-0838-1
  21. Thuss-Patience PC, Hofheinz RD, Arnold D, et al (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, 2827-34. https://doi.org/10.1093/annonc/mds129
  22. Wagner AD, Unverzagt S, Grothe W, et al (2010). Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev, 3, 4064.
  23. Wagner AD, Grothe W, Haerting J, et al (2006). Chemotherapy in advanced gastric cancer: a systematic review and metaanalysis based on aggregate data. J Clin Oncol, 24, 2903-9. https://doi.org/10.1200/JCO.2005.05.0245
  24. Van Cutsem E, Moiseyenko VM, Tjulandin S, 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, 24, 4991-7. https://doi.org/10.1200/JCO.2006.06.8429
  25. Vanhoefer U, Rougier P, Wilke H, et al (2000). Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol, 18, 2648-57.
  26. Yoney A, Isikli L (2013). Can capecitabine be used instead of concurrent bolus 5-FU in postoperative chemoradiotherapy for gastric adenocarcinoma? Asian Pac J Cancer Prev, 14, 5127-31. https://doi.org/10.7314/APJCP.2013.14.9.5127

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