Cancer Chemotherapy and Pharmacology

, Volume 64, Issue 3, pp 455–462 | Cite as

A phase II trial evaluating capecitabine and irinotecan as second line treatment in patients with oesophago-gastric cancer who have progressed on, or within 3 months of platinum-based chemotherapy

  • Alexandra Leary
  • L. Assersohn
  • D. CunninghamEmail author
  • A. R. Norman
  • G. Chong
  • G. Brown
  • P. J. Ross
  • C. Costello
  • L. Higgins
  • J. Oates
Original Article



There is no standard second line therapy for relapsed oesophago-gastric (O-G) cancer.


We recruited 29 eligible patients with relapsed O-G cancer who had progressed during or within 3 months of prior chemotherapy to assess the efficacy and toxicity of capecitabine [2,000 mg/(m2 day) on days 1–14] and irinotecan (250 mg/m2) given every 3 weeks.


Five patients (17%) demonstrated objective response, while a further seven patients (24%) achieved disease stabilisation. Median progression-free survival and overall survival were 3.1 months (95% CI = 2.2–4.1 months) and 6.5 months (95%CI = 6–7.1 months), respectively. Among symptomatic patients, palliation of tumour-related symptoms included resolution of reflux (5/12 pts), dysphagia (3/9 pts) and weight loss (4/9 pts), improvements in anorexia (4/10 pts), nausea (3/4 pts), vomiting (4/6 pts) and pain (4/16 pts). Grade 3–4 toxicities were diarrhoea (15%), nausea and vomiting (7%), lethargy (31%), neutropenia (31%), anemia (14%) and thrombocytopenia (7%).


Capecitabine and irinotecan has anti-tumour activity as second line treatment for relapsed O-G cancer, and provides an important improvement in disease related symptoms.


Gastro-oesophageal cancer Capecitabine Irinotecan Second line chemotherapy 



We are grateful to Roche and Aventis for financial support.


  1. 1.
    International Agency for Research on Cancer (2003) World Cancer ReportGoogle Scholar
  2. 2.
    Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK et al (1997) Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15(1):261–267PubMedGoogle Scholar
  3. 3.
    Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P et al (2002) Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) with epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 20(8):1996–2004PubMedCrossRefGoogle Scholar
  4. 4.
    Thuss-Patience PC, Kretzschmar A, Repp M, Kingreen D, Hennesser D, Micheel S et al (2005) Docetaxel and continuous-infusion fluorouracil versus epirubicin, cisplatin, and fluorouracil for advanced gastric adenocarcinoma: a randomized phase II study. J Clin Oncol 23(3):494–501PubMedCrossRefGoogle Scholar
  5. 5.
    Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M et al (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355(1):11–20PubMedCrossRefGoogle Scholar
  6. 6.
    Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN et al (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345(10):725–730PubMedCrossRefGoogle Scholar
  7. 7.
    Futatsuki K, Wakui A, Nakao I, Sakata Y, Kambe M, Shimada Y et al (1994) Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group. Gan To Kagaku Ryoho 21(7):1033–1038PubMedGoogle Scholar
  8. 8.
    Saltz LB, Douillard JY, Pirotta N, Alakl M, Gruia G, Awad L et al (2001) Irinotecan plus fluorouracil/leucovorin for metastatic colorectal cancer: a new survival standard. Oncologist 6(1):81–91PubMedCrossRefGoogle Scholar
  9. 9.
    Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ et al (2000) Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 343(13):905–914PubMedCrossRefGoogle Scholar
  10. 10.
    Blanke CD, Haller DG, Benson AB, Rothenberg ML, Berlin J, Mori M et al (2001) A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with previously untreated gastric adenocarcinoma. Ann Oncol 12(11):1575–1580PubMedCrossRefGoogle Scholar
  11. 11.
    Pozzo C, Barone C, Szanto J, Padi E, Peschel C, Bukki J et al (2004) Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Ann Oncol 15(12):1773–1781PubMedCrossRefGoogle Scholar
  12. 12.
    Assersohn L, Brown G, Cunningham D, Ward C, Oates J, Waters JS et al (2004) Phase II study of irinotecan and 5-fluorouracil/leucovorin in patients with primary refractory or relapsed advanced oesophageal and gastric carcinoma. Ann Oncol 15(1):64–69PubMedCrossRefGoogle Scholar
  13. 13.
    de Gramont A, Bosset JF, Milan C, Rougier P, Bouche O, Etienne PL et al (1997) Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study. J Clin Oncol 15(2):808–815PubMedGoogle Scholar
  14. 14.
    Rea DW, Nortier JW, Ten Bokkel Huinink WW, Falk S, Richel DJ, Maughan T et al (2005) A phase I/II and pharmacokinetic study of irinotecan in combination with capecitabine as first-line therapy for advanced colorectal cancer. Ann Oncol 16(7):1123–1132PubMedCrossRefGoogle Scholar
  15. 15.
    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):205–216PubMedCrossRefGoogle Scholar
  16. 16.
    Hecht JR, Blanke CD, Benson III AB, Lenz HJ (2003) Irinotecan and paclitaxel in metastatic adenocarcinoma of the esophagus and gastric cardia. Oncology (Williston Park) 17(9 Suppl 8):13–15Google Scholar
  17. 17.
    Kang HJ, Chang HM, Kim TW, Ryu MH, Sohn HJ, Yook JH et al (2005) Phase II study of capecitabine and cisplatin as first-line combination therapy in patients with gastric cancer recurrent after fluoropyrimidine-based adjuvant chemotherapy. Br J Cancer 92(2):246–251PubMedGoogle Scholar
  18. 18.
    Kim ST, Kang WK, Kang JH, Park KW, Lee J, Lee SH et al (2005) Salvage chemotherapy with irinotecan, 5-fluorouracil and leucovorin for taxane- and cisplatin-refractory, metastatic gastric cancer. Br J Cancer 92(10):1850–1854PubMedCrossRefGoogle Scholar
  19. 19.
    Schuller J, Cassidy J, Dumont E, Roos B, Durston S, Banken L et al (2000) Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol 45(4):291–297PubMedCrossRefGoogle Scholar
  20. 20.
    Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M et al (2001) Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 19(8):2282–2292PubMedGoogle Scholar
  21. 21.
    Delord JP, Pierga JY, Dieras V, Bertheault-Cvitkovic F, Turpin FL, Lokiec F et al (2005) A phase I clinical and pharmacokinetic study of capecitabine (Xeloda) and irinotecan combination therapy (XELIRI) in patients with metastatic gastrointestinal tumours. Br J Cancer 92(5):820–826PubMedCrossRefGoogle Scholar
  22. 22.
    Baek JH, Kim JG, Jeon SB, Chae YS, Kim DH, Sohn SK et al (2006) Phase II study of capecitabine and irinotecan combination chemotherapy in patients with advanced gastric cancer. Br J Cancer 94(10):1407–1411PubMedCrossRefGoogle Scholar
  23. 23.
    Hironaka S, Zenda S, Boku N, Fukutomi A, Yoshino T, Onozawa Y (2006) Weekly paclitaxel as second-line chemotherapy for advanced or recurrent gastric cancer. Gastric Cancer 9(1):14–18PubMedCrossRefGoogle Scholar
  24. 24.
    Ajani JA, Baker J, Pisters PW, Ho L, Mansfield PF, Feig BW et al (2002) Irinotecan/cisplatin in advanced, treated gastric or gastroesophageal junction carcinoma. Oncology (Williston Park) 16(5 Suppl 5):16–18Google Scholar
  25. 25.
    Giuliani F, Molica S, Maiello E, Battaglia C, Gebbia V, Di Bisceglie M et al (2005) Irinotecan (CPT-11) and mitomycin-C(MMC) as second-line therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico dell’ Italia Meridionale (prot. 2106). Am J Clin Oncol 28(6):581–585PubMedCrossRefGoogle Scholar
  26. 26.
    Stahl M, Muller C, Koster W, Wilke H (2005) Second-line chemotherapy of advanced disseminated gastric cancer after cisplatin, infusional 5-fluorouracil, folinic acid (PLF): benefit dependent on progression-free interval after first-line therapy. Onkologie 28(10):499–502PubMedCrossRefGoogle Scholar
  27. 27.
    Borner MM, Bernhard J, Dietrich D, Popescu R, Wernli M, Saletti P et al (2005) A randomized phase II trial of capecitabine and two different schedules of irinotecan in first-line treatment of metastatic colorectal cancer: efficacy, quality-of-life and toxicity. Ann Oncol 16(2):282–288PubMedCrossRefGoogle Scholar
  28. 28.
    Koopman M, Antonini NF, Douma J, Wals J, Honkoop AH, Erdkamp FL et al (2007) Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet 370(9582):135–142PubMedCrossRefGoogle Scholar
  29. 29.
    Köhne CH, De Greve J, Hartmann JT, Lang I, Vergauwe P, Becker K et al (2007) Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015. Ann Oncol 19(5):920–926PubMedCrossRefGoogle Scholar
  30. 30.
    Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M et al (2007) Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C study. J Clin Oncol 25(30):4779–4786PubMedCrossRefGoogle Scholar
  31. 31.
    Schmiegel WH, Reinacher-Schick A, Freier W et al (2007) Comparable safety and response rate with bevacizumab in combination with capecitabine/oxaliplatin versus capecitabine/irinotecan in advanced CRC: a randomized phase II study of the AIO GI tumor study group. Proc Am Soc Clin Oncol 25:(abstract 4034)Google Scholar
  32. 32.
    Burge ME, Smith D, Topham C, Jackson DP, Anthoney DA, Halstead F et al (2006) A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma. Br J Cancer 94(9):1281–1286PubMedCrossRefGoogle Scholar
  33. 33.
    Oh SC, Sur HY, Sung HJ, Choi IK, Park SS, Seo JH et al (2007) A phase II study of biweekly dose-intensified oral capecitabine plus irinotecan (bXELIRI) for patients with advanced or metastatic gastric cancer. Br J Cancer 96(10):1514–1519PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Alexandra Leary
    • 1
  • L. Assersohn
    • 1
  • D. Cunningham
    • 1
    Email author
  • A. R. Norman
    • 1
  • G. Chong
    • 1
  • G. Brown
    • 1
  • P. J. Ross
    • 1
  • C. Costello
    • 1
  • L. Higgins
    • 1
  • J. Oates
    • 1
  1. 1.Department of MedicineRoyal Marsden HospitalLondonUK

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