Date of Award

January 2013

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Elena Ratner

Subject Area(s)

Medicine

Abstract

Our treatment protocol for malignant peritoneal mesothelioma (MPM) includes initial cytoreductive surgery with heated intraperitoneal chemotherapy (HIPEC), outpatient catheter-administered intraperitoneal chemotherapy (CAIPEC), and a second cytoreductive surgery with HIPEC. We hypothesized that even distribution of CAIPEC would correlate with better overall survival and fewer side effects; that the pharmacokinetics of HIPEC would be influenced by body surface area (BSA); and that tissue penetration of CAIPEC would exceed that of HIPEC due to the longer dwell time.

We analyzed CT peritoneograms from 38 MPM patients undergoing cisplatin CAIPEC for volume and surface area, and modeled overall survival and post-treatment glomerular filtration rate (GFR) with these as predictors. We collected intraoperative blood and peritoneal fluid samples from 10 patients undergoing oxaliplatin HIPEC, used mass spectrometry to determine fluid platinum levels and modeled these outcomes with BSA as a predictor. We collected intraoperative peritoneal tissue samples from 6 patients undergoing HIPEC and used x-ray fluorescence microscopy to characterize tissue platinum levels.

Decreased mortality was associated with larger surface areas (p=0.02) and smaller volumes of CAIPEC (p=0.03), controlling for age, sex, histologic subtype, and residual disease >0.5cm. Larger volumes were associated with higher post-treatment GFR, controlling for pre-treatment GFR, BSA, surface area and BSA-volume interaction (p=0.02). Higher BSA was associated with lower plasma oxaliplatin (p=0.01), and greater pharmacokinetic advantage (p=0.02). Tissue platinum was highest at second surgery post-HIPEC, lowest at first surgery post-HIPEC, and intermediate at second surgery pre-HIPEC.

CT peritoneography provides parameters associated with overall survival and post-treatment GFR in MPM patients undergoing CAIPEC. In HIPEC patients who receive a BSA-based oxaliplatin dose and carrier fluid volume titrated to achieve a desired flow rate, BSA is a predictor of systemic drug exposure. The direct tissue penetration depth of platinum attributable to multiple courses of CAIPEC is greater, and the tissue distribution of platinum more homogeneous, than that attributable to a single dose of HIPEC.

Comments

This is an Open Access Thesis.

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