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Heated (37°C) oxaliplatin infusion in combination with capecitabine for metastatic colorectal carcinoma: can it reduce neuropathy?

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Abstract

Background/Purpose

Oxaliplatin-associated neuropathy remains a dose-limiting toxicity of the standard chemotherapy regimen of oxaliplatin and capecitabine for metastatic colorectal cancer. No preventive strategy has definitively been established. Because this neuropathy is triggered by cold, we hypothesized that infusing oxaliplatin at 37°C might reduce neuropathy.

Methods

In this open-label pilot feasibility trial, patients with no prior chemotherapy for metastatic colorectal cancer were included. Treatment consisted of capecitabine 1,000 mg/m2 bid on days 1–14 and oxaliplatin 130 mg/m2 on day 1 of a 21-day cycle. The oxaliplatin infusion was administered through a fluid-warming device at a constant temperature of 37°C over 2 h. The primary endpoint was feasibility and drug reactions during the infusion. Secondary endpoints included acute and chronic neuropathy as well as response rate.

Results

Twenty patients were enrolled, and a total of 95 cycles administered. Median cumulative oxaliplatin dose was 735 mg/m2. Apart from one patient with laryngeal spasm, no other infusion-related adverse events were observed. Of the patients, 35% reported grade 3/4 acute dysesthesia or paresthesia according to a patients questionnaire. Chronic neuropathy according to NCI CTC v3.0 was observed in 85% (grade 1) and 15% (grade 2), respectively. The overall response rate was 45% (95% CI 23–67%; 5% complete remission; 40% partial remission) and stable disease was achieved in another 30% of patients.

Conclusion

Administration of heated oxaliplatin in combination with capecitabine is feasible and well tolerated without additional toxicity. While we have observed a relatively low rate of chronic cumulative neuropathy with heated oxaliplatin, this procedure appears not promising enough for us to recommend its further clinical evaluation.

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Authors and Affiliations

  1. Medical Oncology, Kantonsspital Graubünden, Loestrasse 170, CH-7000, Chur, Switzerland

    Richard Cathomas, Gisela Mayer, Ulrich Mey & Roger von Moos

  2. Department of Medical Oncology, Kantonsspital St.Gallen, Rorschacher Strasse 95, CH-9007, St. Gallen, Switzerland

    Dieter Köberle, Thomas Ruhstaller & Andrea Räss

Authors
  1. Richard Cathomas
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  2. Dieter Köberle
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  3. Thomas Ruhstaller
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  4. Gisela Mayer
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  5. Andrea Räss
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  6. Ulrich Mey
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  7. Roger von Moos
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Correspondence to Richard Cathomas.

Additional information

This trial was supported by a research grant from Sanofi Aventis Suisse SA

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Cathomas, R., Köberle, D., Ruhstaller, T. et al. Heated (37°C) oxaliplatin infusion in combination with capecitabine for metastatic colorectal carcinoma: can it reduce neuropathy?. Support Care Cancer 18, 1263–1270 (2010). https://doi.org/10.1007/s00520-009-0740-1

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  • DOI: https://doi.org/10.1007/s00520-009-0740-1

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