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Fixed-dose-rate gemcitabine combined with cisplatin in patients with inoperable biliary tract carcinomas

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Abstract

Background

Biliary tract cancers (BTC) have a poor prognosis, and there is no consensus on the best chemotherapy regimen. This study determined the response rate for fixed-dose-rate (FDR) gemcitabine combined with cisplatin.

Methods

This multicentre phase II trial enrolled 50 patients with inoperable locally advanced or metastatic BTC. Treatment consisted of FDR gemcitabine 1,000 mg/m2 (10 mg/m2/min) and cisplatin 20 mg/m2 on days 1 and 8 of a 21-day cycle. The primary endpoint was response rate. Secondary endpoints included safety, response duration (RD), progression-free (PFS) and overall survival (OS), and cancer antigen 19-9 response.

Results

Thirteen patients (26%, 95% CI 14.6–40.4) had a partial response, and 12 (24%) had stable disease. The median RD was 8.3 months (95% CI 6.91–9.99); median PFS 4 months (95% CI 2.5–6.77); and median OS 6.8 months (95% CI 5.0–8.7). Treatment was well tolerated. Grade 3 and grade 4 nausea, vomiting, and fatigue were uncommon. Thirty-eight per cent of patients discontinued treatment because of toxicity, patient or clinician preference.

Conclusions

This treatment combination had moderate activity with acceptable toxicity, supporting previous results that this combination has a role to play. The study does not suggest that FDR gemcitabine is superior to bolus infusion.

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References

  1. Greenlee RT, Hill-Harmon MB, Murray T et al (2001) Cancer statistics, 2001. CA Cancer J Clin 51:15–36

    Article  CAS  PubMed  Google Scholar 

  2. Patel T (2002) Worldwide trends in mortality from biliary tract malignancies. BMC Cancer 2:10

    Article  PubMed  Google Scholar 

  3. Eckel F, Schmid RM (2007) Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer 96:896–902

    Article  CAS  PubMed  Google Scholar 

  4. Pasetto LM, D’Andrea MR, Falci C et al (2007) Gemcitabine in advanced biliary tract cancers. Crit Rev Oncol Haematol 61:230–242

    Article  Google Scholar 

  5. Abbruzzese JL, Grunewald R, Weeks EA et al (1991) A phase I clinical, plasma and pharmacology study of gemcitabine. J Clin Oncol 9:491–498

    CAS  PubMed  Google Scholar 

  6. Tempero M, Plunkett W, van Haperen VR et al (2003) Randomised phase II comparison of fixed dose-intense gemcitabine: thirty minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol 21:3402–3408

    Article  CAS  PubMed  Google Scholar 

  7. Poplin E, Feng Y, Berlin J et al (2009) Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the eastern cooperative oncology. J Clin Oncol 27:3778–3785

    Article  CAS  PubMed  Google Scholar 

  8. Peters GJ, Bergman AM, Ruiz van Haperen VW et al (1995) Interaction between cisplatin and gemcitabine in vitro and in vivo. Semin Oncol 22:72–79

    CAS  PubMed  Google Scholar 

  9. Van Moorsel CJ, Pinedo HM, Veerman G et al (1999) Mechanisms of synergism between cisplatin and gemcitabine in ovarian and non-small cell lung cancer cell lines. Br J Cancer 80:981–990

    Article  PubMed  Google Scholar 

  10. Valle JW, Wasan HS, Palmer DD et al (2009) Gemcitabine with or without cisplatin in patients with advanced or metastatic biliary tract cancer: results of a multicenter, randomized phase III trial (the UK ABC-02 trial). J Clin Oncol 27:15s (abstract 4503)

    Google Scholar 

  11. Ko A, Dito E, Schillinger B et al (2006) Phase II study of fixed dose rate gemcitabine with cisplatin for metastatic adenocarcinoma of the pancreas. J Clin Oncol 24:379–385

    Article  CAS  PubMed  Google Scholar 

  12. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216

    Article  CAS  PubMed  Google Scholar 

  13. Rustin GJ, Nelstrop AE, McClean P et al (1996) Defining response of ovarian carcinoma to initial chemotherapy according to serum CA 125. J Clin Oncol 14:1545–1551

    CAS  PubMed  Google Scholar 

  14. Meyerhardt JA, Zhu A, Stuart K et al (2008) Phase II study of gemcitabine and cisplatin in patients with metastatic biliary and gallbladder cancer. Dig Dis Sci 53:564–570

    Article  CAS  PubMed  Google Scholar 

  15. Lee J, Kim TY, Lee MA et al (2008) Phase II trial of gemcitabine combined with cisplatin in patients with inoperable biliary tract carcinomas. Cancer Chemother Pharmacol 61:47–52

    Article  CAS  PubMed  Google Scholar 

  16. Giuliani F, Gebbia V, Maiello E et al (2006) Gemcitabine and cisplatin for inoperable and/or metastatic biliary tree carcinomas: a multicentre phase II study of the Gruppo Oncologica dell’Italia Meridionale. Ann Oncol 17:vii73–vii77

    Article  PubMed  Google Scholar 

  17. Park BK, Kim YJ, Park JY et al (2006) Phase II study of gemcitabine and cisplatin in advanced biliary tract cancer. J Gastronenterol Hepatol 21:993–1003

    Google Scholar 

  18. Kim ST, Park JO, Lee J et al (2006) A phase II study of gemcitabine and cisplatin in advanced biliary tract cancer. Cancer 106:1339–1346

    Article  CAS  PubMed  Google Scholar 

  19. Thongprasert S, Napapan S, Charoentum C et al (2005) Phase II study of gemcitabine and cisplatin as first line chemotherapy in inoperable biliary tract carcinoma. Ann Oncol 16:279–281

    Article  CAS  PubMed  Google Scholar 

  20. Doval DC, Sekhon JS, Gupta SK et al (2004) A phase II study of gemcitabine and cisplatin in chemotherapy naïve, unresectable gallbladder cancer. Br J Cancer 90:1516–1520

    Article  CAS  PubMed  Google Scholar 

  21. Reyes-Vidal J, Gallardo J, Yanez E et al (2003) Gemcitabine and cisplatin in the treatment of patients with unresectable or metastatic gallbladder cancer: results of the phase II GOCCHI study. Proc Am Soc Clin 22:273 abstract 1095

    Google Scholar 

  22. Lee GW, Kang JH, Kim HG et al (2006) Combination chemotherapy with gemcitabine and cisplatin as first line treatment for immunohistochemically proven cholangiocarcinoma. Am J Clin Oncol 29:127–131

    Article  CAS  PubMed  Google Scholar 

  23. Ko AH, Hwang J, Venook AP et al (2005) Serum CA19–9 response as a surrogate for clinical outcome in patients receiving fixed dose rate gemcitabine for advanced pancreatic cancer. Br J Cancer 93:195–199

    Article  CAS  PubMed  Google Scholar 

  24. Harder J, Kummer O, Olschewski M et al (2007) Prognostic relevance of Carbohydrate Antigen 19.9 levels in patients with advanced biliary tract cancer. Cancer Epidemiol Biomarkers Prev 16:2097–2100

    Article  CAS  PubMed  Google Scholar 

  25. Riechelmann RP, Townsley CA, Chin SN et al (2007) Expanded phase II trial of gemcitabine and capecitabine for advanced biliary cancer. Cancer 110:1307–1312

    Article  CAS  PubMed  Google Scholar 

  26. Iyer RV, Gibbs J, Kuvshinoff B et al (2007) A phase II study of gemcitabine and capecitabine in advanced cholangiocarcinoma and carcinoma of the gallbladder. A single institution study. Ann Surg Oncol 14:3202–3209

    Article  PubMed  Google Scholar 

  27. Andre T, Tournigand C, Rosmorduc O et al (2004) Gemcitabine combined with oxaliplatin in advanced biliary tract adenocarcinoma. A GERCOR study. Ann Oncol 15:1339–1343

    Article  CAS  PubMed  Google Scholar 

  28. Verderame F, Russo A, Di Leo R et al (2006) Gemcitabine and oxaliplatin combination chemotherapy in advanced biliary tract cancers. Ann Oncol 17(suppl 7):68–72

    Google Scholar 

  29. Park SH, Park YH, Lee JN et al (2006) Phase II study of epirubicin, cisplatin and capecitabine for advanced biliary tract adenocarcinoma. Cancer 106:361–365

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Numerous individuals from many institutions participated to complete this study. The authors thank everyone involved for their efforts. This work was supported by an unrestricted educational grant from Eli Lilly, a Partnership grant from the Cancer Institute NSW, and by the National Health and Medical Research Council Clinical Trials Centre.

Conflict of interest statement

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Prince of Wales Hospital, Barker Street, Randwick, NSW, 2031, Australia

    David Goldstein

  2. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia

    M. Corona Gainford, Chris Brown, Val Gebski & Danielle Miller

  3. Austin Health, Melbourne, VIC, Australia

    Niall Tebbutt

  4. Department of Medical Oncology, Calvary Mater Newcastle Hospital, Hunter Medical Research Institute Cancer Research Program, Newcastle, NSW, Australia

    Stephen P. Ackland

  5. Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA, Australia

    Guy van Hazel

  6. Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Michael Jefford

  7. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia

    Michael Jefford

  8. Tweed Cancer Care Centre, Tweed Heads, NSW, Australia

    Ehtesham Abdi

  9. Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia

    Sid Selva-Nayagam

  10. Sydney West Cancer Network, Nepean Cancer Care Centre, Sydney, NSW, Australia

    Jenny Shannon

Authors
  1. David Goldstein
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  2. M. Corona Gainford
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  3. Chris Brown
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  5. Stephen P. Ackland
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  6. Guy van Hazel
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  7. Michael Jefford
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  8. Ehtesham Abdi
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  9. Sid Selva-Nayagam
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  10. Val Gebski
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  11. Danielle Miller
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  12. Jenny Shannon
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Corresponding author

Correspondence to David Goldstein.

Additional information

For the Australasian Gastrointestinal Trials Group.

Trial registration: ACTRN12605000001695.

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Goldstein, D., Gainford, M.C., Brown, C. et al. Fixed-dose-rate gemcitabine combined with cisplatin in patients with inoperable biliary tract carcinomas. Cancer Chemother Pharmacol 67, 519–525 (2011). https://doi.org/10.1007/s00280-010-1351-8

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  • DOI: https://doi.org/10.1007/s00280-010-1351-8

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