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A multi-center phase II study of oxaliplatin, irinotecan, and capecitabine in advanced gastric/gastroesophageal junction carcinoma

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Abstract

Background

There is no standard first-line therapy for advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma and the prognosis remains poor. Our institution conducted a phase I study of oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule. The regimen was tolerated; pharmacodynamic studies revealed no drug interactions, and there was one confirmed response in a gastric cancer patient. We performed a phase II trial in advanced gastric and GEJ adenocarcinoma to determine response rate and response duration.

Methods

This was a multi-center single treatment arm study involving six sites. Only prior adjuvant therapy was allowed. Patients had ECOG performance status of 0–2, adequate organ function, and were able to tolerate oral medications. All patients received oxaliplatin 60 mg/m2 intravenously (IV) and irinotecan 50 mg/m2 IV weekly times 4 weeks with a 2-week rest period. Capecitabine 450 mg bid orally was received on days 1 through 5 every week for 4 weeks, followed by a 2-week rest. Patients were assessed for response after the first two cycles; response duration, overall survival, and adverse events were also recorded. We estimated an improvement in historical response rate by 30% would have clinical meaning.

Results

A total of 39 patients were accrued and all were assessed for toxicity; 30 patients were evaluable for response. The median age was 57.8 years (31–79 years) and 74% were male. Two patients had a complete response, with nine patients achieving a partial response. The total response rate was 28%, with nine patients not evaluable for response. The median response duration was noted at 5.97 months and median overall survival was 8.98 months. There were no grade 5 treatment related events, with all deaths secondary to disease progression. Only five grade 4 events occurred (neutropenia, hyperkalemia, hypokalemia (2), thrombosis/embolism) without grade 4 diarrhea or sensory neuropathy.

Conclusions

Oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule does induce responses in advanced gastric and GEJ adenocarcinoma. However, the total response rate is modest and not an improvement over other regimens.

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Acknowledgments

Supported by NIH grant U01 CA62502.

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Authors and Affiliations

  1. Developmental Therapeutics Program, Case Comprehensive Cancer Center, Cleveland, OH, USA

    Joanna M. Brell, Smitha S. Krishnamurthi, Afshin Dowlati & Linda Rath

  2. Department of Medicine, University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, OH, 44106-5055, USA

    Joanna M. Brell, Smitha S. Krishnamurthi, Afshin Dowlati & Linda Rath

  3. Roswell Park Cancer Institute, Buffalo, NY, USA

    Milind Javle

  4. Lake University Ireland Cancer Center, Mentor, OH, USA

    Joel Saltzman

  5. Henry Ford Health System, Detroit, MI, USA

    Ira Wollner

  6. Cleveland Clinic Foundation, Cleveland, OH, USA

    Robert Pelley

  7. Community Health Partners, Elyria, OH, USA

    Belagodu N. Kantharaj

  8. Division of Biostatistics, Case Comprehensive Cancer Center, Cleveland, OH, USA

    Mark D. Schluchter

  9. Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, USA

    S. Percy Ivy

  10. Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, USA

    Scot C. Remick

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  1. Joanna M. Brell
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Correspondence to Joanna M. Brell.

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Brell, J.M., Krishnamurthi, S.S., Javle, M. et al. A multi-center phase II study of oxaliplatin, irinotecan, and capecitabine in advanced gastric/gastroesophageal junction carcinoma. Cancer Chemother Pharmacol 63, 851–857 (2009). https://doi.org/10.1007/s00280-008-0807-6

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  • DOI: https://doi.org/10.1007/s00280-008-0807-6

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