Cancer Chemotherapy and Pharmacology

, Volume 73, Issue 4, pp 839–845 | Cite as

A phase II study of capecitabine plus docetaxel in gemcitabine-pretreated metastatic pancreatic cancer patients: CapTere

  • Heloisa P. Soares
  • Soley Bayraktar
  • Marcelo Blaya
  • Gilberto Lopes
  • Jaime Merchan
  • Jessica Macintyre
  • Carlos Mayo
  • Mark R. Green
  • Orlando Silva
  • Joe Levi
  • Gail Walker
  • Caio M. Rocha-Lima
Original Article

Abstract

Purpose

Docetaxel and capecitabine combination is synergistic in preclinical models. We investigated the efficacy and toxicity of this combination as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma (mPC), pretreated with gemcitabine-based chemotherapy.

Methods

Eligible patients were treated with capecitabine 800 mg/m2 orally PO bid on days 1–14 in combination with intravenous docetaxel 30 mg/m2 on days 1 and 8 of each 21-day cycle. The primary end point was overall response rate. Using a three-stage sequential design, two interim analyses for early stopping due to lack of efficacy were planned and conducted after 13 and 26 patients were accrued. Secondary end points included time to treatment failure, progression-free survival (PFS), overall survival (OS) and 50 % drop in CA19-9 levels.

Results

Forty-three patients were evaluable for toxicity and 42 evaluable for response, at a median age of 64 years. The majority of patients (74 %) had ECOG PS 0-1. Six patients (14 %) achieved a partial tumor response, and stable disease for ≥2 cycles was observed in 59 % of patients (n = 25). Thirty-five percent (n = 11/31) of patients had a ≥50 % decrease in CA19-9 levels. The median PFS was 3.7 months (95 % CI 2.1–4.3 months), and the median OS was 5.3 months (95 % CI 4.3–8.6 months). Treatment was generally well tolerated. Grade 3 toxicity and grade 4 toxicity were seen in 45 and 5 % of patients, respectively. One patient had a potential treatment-related mortality.

Conclusions

The combination of capecitabine and docetaxel is active and well tolerated in mPC patients pretreated with gemcitabine-based therapy.

Keywords

Pancreatic cancer Gemcitabine pretreated Second-line chemotherapy Capecitabine Docetaxel 

References

  1. 1.
  2. 2.
    Conroy T, Desseigne F, Ychou M et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825PubMedCrossRefGoogle Scholar
  3. 3.
    Von Hoff DD, Ervin T, Arena FP, Gabriela Chiorean E, Infante JR, Moore MJ et al (2013) Results of a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas with PET and CA19-9 correlates. In: ASCO annual meeting. Chicago, IL. J Clin Oncol 31: abstract 4005Google Scholar
  4. 4.
    Oettle H, Pelzer U, Stieler J et al (2005) Oxaliplatin/folinic acid/5-fluorouracil [24 h] (OFF) plus best supportive care versus best supportive care alone (BSC) in second-line therapy of gemcitabine-pretreated advanced pancreatic cancer (CONKO 003). In: ASCO annual meeting proceedings 2005. J Clin Oncol 23: abstract 4031Google Scholar
  5. 5.
    Pelzer U, Kubica K, Stieler J et al (2008) A randomized trial in patients with gemcitabine pretreated pancreatic cancer. Final results of the CONKO 003 study. In: ASCO annual meeting proceedings. J Clin Oncol 26: abstract 4508Google Scholar
  6. 6.
    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 47:1676–1681PubMedCrossRefGoogle Scholar
  7. 7.
    Fujimoto-Ouchi K, Tanaka Y, Tominaga T (2001) Schedule dependency of antitumor activity in combination therapy with capecitabine/5′-deoxy-5-fluorouridine and docetaxel in breast cancer models. Clin Cancer Res 7:1079–1086PubMedGoogle Scholar
  8. 8.
    Maher JF, Villalona-Calero MA (2002) Taxanes and capecitabine in combination: rationale and clinical results. Clin Breast Cancer 2:287–293PubMedCrossRefGoogle Scholar
  9. 9.
    O’Shaughnessy JA, Blum JL (2006) Capecitabine/taxane combination therapy: evolving clinical utility in breast cancer. Clin Breast Cancer 7:42–50PubMedCrossRefGoogle Scholar
  10. 10.
    O’Shaughnessy J, Miles D, Vukelja S et al (2002) Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 20:2812–2823PubMedCrossRefGoogle Scholar
  11. 11.
    Androulakis N, Kourousis C, Dimopoulos MA et al (1999) Treatment of pancreatic cancer with docetaxel and granulocyte colony-stimulating factor: a multicenter phase II study. J Clin Oncol 17:1779–1785PubMedGoogle Scholar
  12. 12.
    Rougier P, Adenis A, Ducreux M et al (2000) A phase II study: docetaxel as first-line chemotherapy for advanced pancreatic adenocarcinoma. Eur J Cancer 36:1016–1025PubMedCrossRefGoogle Scholar
  13. 13.
    Boeck S, Wilkowski R, Bruns CJ et al (2007) Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer. Oncology 73:221–227PubMedCrossRefGoogle Scholar
  14. 14.
    Kulke MH, Blaszkowsky LS, Ryan DP et al (2007) Capecitabine plus erlotinib in gemcitabine-pretreated advanced pancreatic cancer. J Clin Oncol 25:4787–4792PubMedCrossRefGoogle Scholar
  15. 15.
    Xiong HQ, Varadhachary GR, Blais JC et al (2008) Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer 113:2046–2052PubMedCrossRefGoogle Scholar
  16. 16.
    van Meerten ELP, Gelderblom H, Bloem JL (2010) RECIST revised: implications for the radiologist. A review article on the modified RECIST guideline. Eur Radiol 20:1456–1467CrossRefGoogle Scholar
  17. 17.
    Saif MW, Syrigos K, Penney R, Kaley K (2010) Docetaxel second-line therapy in patients with advanced pancreatic cancer: a retrospective study. Anticancer Res 30:2905–2909PubMedGoogle Scholar
  18. 18.
    Katopodis O, Polyzos A, Kentepozidis N et al (2011) Second-line chemotherapy with capecitabine (Xeloda) and docetaxel (Taxotere) in previously treated, unresectable adenocarcinoma of pancreas: the final results of a phase II trial. Cancer Chemother Pharmacol 67:361–368PubMedCrossRefGoogle Scholar
  19. 19.
    Chua YJ, Cunningham D (2006) Chemotherapy for advanced pancreatic cancer. Best Pract Res Clin Gastroenterol 20:327–348PubMedCrossRefGoogle Scholar
  20. 20.
    Fine R, Moorer G, Sherman W, Chu, Maurer KM, Chabot J et al (2009) Phase II trial of GTX chemotherapy in metastatic pancreatic cancer. Clin Oncol 27(15 Suppl): abstract 4623Google Scholar
  21. 21.
    Ulrich-Pur H, Raderer M, Verena Kornek G et al (2003) Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma. Br J Cancer 88:1180–1184Google Scholar
  22. 22.
    Jacobs AD, Burris HA, Rivkin S et al (2004) A randomized phase III study of rubitecan (ORA) vs. best choice (BC) in 409 patients with refractory pancreatic cancer report from a North-American multi-center study. J Clin Oncol 22(Suppl):Abstr 4013Google Scholar
  23. 23.
    Astsaturov IA, Meropol NJ, Alpaugh RK et al (2007) A randomized phase II and coagulation study of bevacizumab alone or with docetaxel in patients with previously treated metastatic pancreatic adenocarcinoma. J Clin Oncol 25(18S):Abstr 4556Google Scholar
  24. 24.
    Hwang JY, Yoo C, Kim T et al (2009) A randomized phase II study of FOLFOX or FOLFIRI.3 as second-line therapy in patients with advanced pancreatic cancer previously treated with gemcitabine-based chemotherapy. J Clin Oncol 27(15S):Abstr 4618Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Heloisa P. Soares
    • 1
  • Soley Bayraktar
    • 1
  • Marcelo Blaya
    • 2
  • Gilberto Lopes
    • 3
  • Jaime Merchan
    • 1
  • Jessica Macintyre
    • 1
  • Carlos Mayo
    • 1
  • Mark R. Green
    • 1
  • Orlando Silva
    • 1
  • Joe Levi
    • 1
  • Gail Walker
    • 1
  • Caio M. Rocha-Lima
    • 1
  1. 1.Division of Hematology/Oncology, Sylvester Comprehensive Cancer CenterUniversity of MiamiMiamiUSA
  2. 2.Tulane UniversityNew OrleansUSA
  3. 3.Johns Hopkins Singapore International Medical CenterSingaporeRepublic of Singapore

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