Annals of Surgical Oncology

, Volume 15, Issue 8, pp 2137–2145 | Cite as

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

  • John H. StewartIV
  • Perry Shen
  • Greg Russell
  • Joyce Fenstermaker
  • Libby McWilliams
  • Faith M. Coldrun
  • Keith E. Levine
  • Bradley T. Jones
  • Edward A. Levine
Gastrointestinal Oncology

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.

Keywords

Oxaliplatin Surgery Intraperitoneal hyperthermic chemoperfusion Carcinomatosis Phase I trial 

Notes

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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Copyright information

© Society of Surgical Oncology 2008

Authors and Affiliations

  • John H. StewartIV
    • 1
  • Perry Shen
    • 1
  • Greg Russell
    • 2
  • Joyce Fenstermaker
    • 1
  • Libby McWilliams
    • 1
  • Faith M. Coldrun
    • 3
  • Keith E. Levine
    • 4
  • Bradley T. Jones
    • 5
  • Edward A. Levine
    • 1
  1. 1.Surgical Oncology Service, Department of General Surgery, Medical Center BlvdWake Forest University School of MedicineWinston-SalemUSA
  2. 2.Biostatistics Section, Department of Public Health SciencesWake Forest University School of MedicineWinston-SalemUSA
  3. 3.Department of PhysicsWake Forest UniversityWinston-SalemUSA
  4. 4.Research Triangle InstituteResearch Triangle ParkUSA
  5. 5.Department of ChemistryWake Forest UniversityWinston-SalemUSA

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