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Second-Line Capecitabine and Oxaliplatin Combination for Gemcitabine-Resistant Advanced Pancreatic Cancer

  • Bayoglu, Ibrahim Vedat (Department of Medical Oncology, Izmir Katip Celebi University Ataturk Training and Research Hospital) ;
  • Varol, Umut (Department of Medical Oncology, Izmir Katip Celebi University Ataturk Training and Research Hospital) ;
  • Yildiz, Ibrahim (Department of Medical Oncology, Izmir Katip Celebi University Ataturk Training and Research Hospital) ;
  • Muslu, Ugur (Department of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University) ;
  • Alacacioglu, Ahmet (Department of Medical Oncology, Izmir Katip Celebi University Ataturk Training and Research Hospital) ;
  • Kucukzeybek, Yuksel (Department of Medical Oncology, Izmir Katip Celebi University Ataturk Training and Research Hospital) ;
  • Akyol, Murat (Department of Medical Oncology, Izmir Katip Celebi University Ataturk Training and Research Hospital) ;
  • Demir, Lutfiye (Department of Medical Oncology, Izmir Katip Celebi University Ataturk Training and Research Hospital) ;
  • Dirican, Ahmet (Department of Medical Oncology, Izmir Katip Celebi University Ataturk Training and Research Hospital) ;
  • Cokmert, Suna (Department of Medical Oncology, Izmir Katip Celebi University Ataturk Training and Research Hospital) ;
  • Yildiz, Yasar (Department of Medical Oncology, Izmir Katip Celebi University Ataturk Training and Research Hospital) ;
  • Karabulut, Bulent (Department of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University) ;
  • Uslu, Ruchan (Department of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University) ;
  • Tarhan, Mustafa Oktay (Department of Medical Oncology, Izmir Katip Celebi University Ataturk Training and Research Hospital)
  • Published : 2014.09.15

Abstract

Background: The role of second-line therapy in metastatic pancreatic cancer is not clear. In this study, we aimed to explore the second-line efficiency of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer who have received gemcitabine-based first-line therapy. Materials and Methods: We retrospectively evaluated 47 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine-based first-line regimens. Treatment consisted of oxaliplatin $130mg/m^2$ and capecitabine $1000mg/m^2$ twice daily with a 3 week interval, until unacceptable toxicity or disease progression. Results: Median number of cycles was 4 (range, 2-10). The overall disease control rate was 38.3%. The median overall survival and progression-free survival from the start of second-line therapy were 23 weeks (95%CI: 16.6-29.5 weeks) and 12 weeks (95%CI: 9.8-14.4 weeks), respectively. The most common grade 3-4 toxicities were nausea, vomiting and hematologic side effects. Conclusions: Our result suggests that the combination of capecitabine and oxaliplatin was tolerated with manageable toxicity and showed encouraging activity as second-line treatment of advanced or metastatic pancreatic cancer patients with ECOG performance status 0-2.

Keywords

Capecitabine;oxaliplatin;advanced pancreatic cancer;second-line treatment

References

  1. Boeck S, Weigang-Kohler K, Fuchs M, et al (2007). Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter phase II trial. Ann Oncol, 18, 745-51.
  2. Burris HA, III, Moore MJ, Andersen J et al (1997). Improvements in survival and clinical benefit with gemcitabine as first- line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol, 15, 2403-13.
  3. Canyilmaz E, Serdar L, Uslu GH, et al (2013). Evaluation of prognostic factors and survival results in pancreatic carcinomas in Turkey. Asian Pac J Cancer Prev, 14, 6573-8. https://doi.org/10.7314/APJCP.2013.14.11.6573
  4. Chen WQ, Liang D, Zhang SW, et al (2013). Pancreatic cancer incidence and mortality patterns in china, 2009. Asian Pac J Cancer Prev, 14, 7321-4. https://doi.org/10.7314/APJCP.2013.14.12.7321
  5. Cheung R (2013). Racial and social economic factors impact on the cause specific survival of pancreatic cancer: a SEER survey. Asian Pac J Cancer Prev, 14, 159-63. https://doi.org/10.7314/APJCP.2013.14.1.159
  6. Choi JG, Seo JH, Oh SC, et al (2012). A Phase II Trial of Gemcitabine plus Capecitabine for Patients with Advanced Pancreatic Cancer. Cancer Res Treat, 44, 127-32. https://doi.org/10.4143/crt.2012.44.2.127
  7. Choi M, Saif MW, Kim R (2014). Is there a role for second line therapy in advanced pancreatic cancer? JOP, 15, 106-9.
  8. Conroy T, Desseigne F, Ychou M, et al (2011). FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. The New England Journal of Medicine, 364, 1817-25 https://doi.org/10.1056/NEJMoa1011923
  9. Demols A, Peeters M, Polus M, et al (2006). Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study. Br J Cancer, 94, 481-5. https://doi.org/10.1038/sj.bjc.6602966
  10. Diaz-Rubio E, Evans TR, Tabemero Jet al (2002). Capecitabine (Xeloda) in combination with oxaliplatin: a phase I, doseescalation study in patients with advanced or metastatic solid tumors. Ann Oncol, 13, 558-65. https://doi.org/10.1093/annonc/mdf065
  11. 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
  12. Faivre S, Raymond E, Woynarowski JM, et al (1999). Supraadditive effect of 2',2' difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines. Cancer Chemother Pharmacol, 44, 117-23. https://doi.org/10.1007/s002800050955
  13. Fernandez E, La Vecchia C, Porta M, et al (1994). Trends in pancreatic cancer mortality in Europe, 1955-1989. Int J Cancer, 57, 786-92 https://doi.org/10.1002/ijc.2910570605
  14. Fesinmeyer MD, Austin MA, Li CI, et al (2005). Differences in survival by histologic type of pancreatic cancer. Cancer Epidemiol Biomarkers Prev, 14, 1766-73. https://doi.org/10.1158/1055-9965.EPI-05-0120
  15. Glimelius B, Hoffman K, Sjoden PO, et al (1996). Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol, 7, 593-600. https://doi.org/10.1093/oxfordjournals.annonc.a010676
  16. Herrmann C, Abel U, Stremmel W, et al (2007). Short time to progression under first-line chemotherapy is a negative prognostic factor for time to progression and residual survival under second-line chemotherapy in advanced pancreatic cancer. Oncology, 73, 335-9. https://doi.org/10.1159/000134477
  17. Ignatiadis M, Polyzos A, Stathopoulos GP, et al (2006). A multicenter phase II study of docetaxel in combination with gefitinib in gemcitabine-pretreated patients with advanced/metastatic pancreatic cancer. Oncology, 71, 159-63. https://doi.org/10.1159/000106064
  18. Inal A, Ciltas A, Yildiz R, et al (2012). Long term survivors with metastatic pancreatic cancer treated with gemcitabine alone or plus cisplatin: a retrospective analysis of an Anatolian Society of Medical Oncology multicenter study. Asian Pac J Cancer Prev, 13, 1841-4. https://doi.org/10.7314/APJCP.2012.13.5.1841
  19. Kim ST, Choi YJ, Park KH, et al (2012). A prognostic model to identify patients with advanced pancreas adenocarcinoma who could benefit from second-line chemotherapy. Clin Oncol (R Coll Radiol), 2, 105-11
  20. Klapdor R, Fenner C (2000). Irinotecan (Campto R): efficacy as third/fourth line therapy in advanced pancreatic cancer. Anticancer Res, 20, 5209-12.
  21. Kulke MH, Blaszkowsky LS, Ryan DP, et al (2007). Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol, 25, 4787-92. https://doi.org/10.1200/JCO.2007.11.8521
  22. Luke C, Price T, Karapetis C, et al (2009). Pancreatic cancer epidemiology and survival in an Australian population. Asian Pac J Cancer Prev, 10, 369-74.
  23. Mitry E, Ducreux M, Ould-Kaci M, et al (2006). Oxaliplatin combined with 5- FU in second line treatment of advanced pancreatic adenocarcinoma. Results of a phase II trial. Gastroenterol Clin Biol, 30, 357-63. https://doi.org/10.1016/S0399-8320(06)73188-8
  24. Neoptolemos JP, Cunningham D, Friess H, et al (2003). Adjuvant therapy in pancreatic cancer: historical and current perspectives. Ann Oncol, 14, 675-92 https://doi.org/10.1093/annonc/mdg207
  25. Oken MM, Creech RH, Tormey DC, et al (1982). Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol, 6, 649-55.
  26. Pelzer U, Schwaner I, Stieler J, et al (2011). Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer, 47, 1676-81 https://doi.org/10.1016/j.ejca.2011.04.011
  27. Qureshi A, Hassan U, Azam M. (2011). Morphology, TNM staging and survival with pancreatico-duodenectomy specimens received at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Pakistan. Asian Pac J Cancer Prev, 12, 953-6.
  28. Reigner B, Blesch K, Weidekamm E (2001) Clinical pharmacokinetics of capecitabine. Clin Pharmacokinet, 40, 85-104. https://doi.org/10.2165/00003088-200140020-00002
  29. Reni M, Pasetto L, Aprile G, et al (2006). Raltitrexed-eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer. Br J Cancer, 94, 785-91. https://doi.org/10.1038/sj.bjc.6603026
  30. Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, 2013. CA Cancer J Clin, 63, 11-30 https://doi.org/10.3322/caac.21166
  31. Tokh M, Bathini V, Saif MW (2012). First-line treatment of metastatic pancreatic cancer. JOP, 13, 159-62
  32. Trotti A, Colevas AD, Setser A, et al (2003). CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol, 13,176-81. https://doi.org/10.1016/S1053-4296(03)00031-6
  33. Tsavaris N, Kosmas C, Skopelitis H, et al (2005). Second-line treatment with oxaliplatin, leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer: A phase II study. Invest New Drugs, 23, 369-75. https://doi.org/10.1007/s10637-005-1446-y
  34. Von Hoff DD, Goodwin AL, Garcia L (1998). Advances in the treatment of patients with pancreatic cancer: Improvement in symptoms and survivial time. Br J Cancer, 78, 9-13
  35. Xiong HQ, Varadhachary GR, Blais JC, et al (2008). Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as secondline therapy for patients with advanced pancreatic cancer. Cancer, 113, 2046-52 https://doi.org/10.1002/cncr.23810
  36. Zahir S, Arjmand A, Kargar S, et al (2013). Incidence and trends of malignant and benign pancreatic lesions in Yazd, Iran between 2001 and 2011. Asian Pac J Cancer Prev, 14, 2631-5. https://doi.org/10.7314/APJCP.2013.14.4.2631

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