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A Phase I Trial of Oxaliplatin for Intraperitoneal Hyperthermic Chemoperfusion for the Treatment of Peritoneal Surface Dissemination from Colorectal and Appendiceal Cancers

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 07 March 2012

Abstract

Background

Cytoreductive surgery with intraperitoneal hyperthermic chemoperfusion (IPHC) has evolved into a promising approach for peritoneal surface malignancy. A large body of literature suggests that oxaliplatin has excellent cytotoxicity against colorectal cancer. Therefore, we undertook a phase I evaluation of IPHC with oxaliplatin for peritoneal dissemination from colorectal and appendiceal cancers to establish the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD).

Methods

Cohorts of three patients underwent cytoreductive surgery followed by a 2-h IPHC with escalating doses of oxaliplatin at a target outflow temperature of 40°C. The initial peritoneal oxaliplatin dose was 200 mg/M2 with increases planned in 50 mg/M2 increments. Plasma and perfusate samples were collected during the IPHC and evaluated using emission spectrometry techniques. Normal tissue and tumor samples were collected before and after the IPHC for analysis. DLT was defined as a grade 3 toxicity lasting 5 days.

Results

Fifteen patients were enrolled at two dose levels. Peritoneal fluid areas under the curve (AUCs) were above those of plasma. Additionally, intratumoral oxaliplatin was similar to that of surrounding normal tissue. Dose-limiting toxicities at 250 mg/M2 were observed in two of three patients enrolled in this study.

Conclusion

We found that IPHC with 200 mg/M2 of oxaliplatin is well tolerated and is the MTD for a 2-h chemoperfusion. Higher doses are not feasible with this perfusion protocol given the significant toxicities associated with 250 mg/M2 oxaliplatin. Based on the data from this phase I study, we propose to conduct further studies with oxaliplatin delivered at 200 mg/M2.

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Acknowledgements

This study was supported by an Investigator Sponsored Trial grant from Sanofi–Aventis. The authors wish to acknowledge James E. Medlin, Kathryn E. Pharr, Summer N. Hanna, Jiyan Gu, Amal S. Essader, and Carl G. Young for their assistance in evaluating platinum levels in the clinical samples.

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Authors and Affiliations

  1. Surgical Oncology Service, Department of General Surgery, Medical Center Blvd, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA

    John H. Stewart IV MD, Perry Shen MD, Joyce Fenstermaker RN, Libby McWilliams BS & Edward A. Levine MD

  2. Biostatistics Section, Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Greg Russell MS

  3. Department of Physics, Wake Forest University, Winston-Salem, NC, USA

    Faith M. Coldrun MS

  4. Research Triangle Institute, Research Triangle Park, NC, USA

    Keith E. Levine PhD

  5. Department of Chemistry, Wake Forest University, Winston-Salem, NC, USA

    Bradley T. Jones PhD

Authors
  1. John H. Stewart IV MD
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  2. Perry Shen MD
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  3. Greg Russell MS
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  4. Joyce Fenstermaker RN
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  5. Libby McWilliams BS
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  6. Faith M. Coldrun MS
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  7. Keith E. Levine PhD
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  8. Bradley T. Jones PhD
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  9. Edward A. Levine MD
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Corresponding author

Correspondence to John H. Stewart IV MD.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1245/s10434-012-2308-4.

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Stewart, J.H., Shen, P., Russell, G. et al. A Phase I Trial of Oxaliplatin for Intraperitoneal Hyperthermic Chemoperfusion for the Treatment of Peritoneal Surface Dissemination from Colorectal and Appendiceal Cancers. Ann Surg Oncol 15, 2137–2145 (2008). https://doi.org/10.1245/s10434-008-9967-1

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  • DOI: https://doi.org/10.1245/s10434-008-9967-1

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