title: Impact of surgical and clinical factors on the pharmacology of intraperitoneal doxorubicin in 145 patients with peritoneal carcinomatosis.
abstract: BACKGROUND
  Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a combined treatment modality considered for selected patients with peritoneal carcinomatosis from colorectal and appendiceal cancer. Doxorubicin is a drug consistently used by our group in this clinical setting. The surgical and clinical factors that modify the pharmacokinetics of HIPEC may be important for the design of future perioperative chemotherapy regimens.
  
  
  METHODS
  The patients included were 145 who had colorectal or appendiceal carcinomatosis resected using CRS prior to treatment with HIPEC with doxorubicin as part of a multidrug regimen. The effect of clinical and surgical factors on drug distribution after a single intraperitoneal bolus administration with doxorubicin was determined.
  
  
  RESULTS
  The pharmacokinetics of 145 patients treated with intraperitoneal doxorubicin showed a 78 times greater exposure to peritoneal surfaces as compared to plasma. At 90 min 12% of the drug remained in the chemotherapy solution and 88% was retained in the body. The extent of visceral resection and peritonectomy increased the clearance of doxorubicin from the peritoneal space. A major resection of visceral peritoneal surface, a contracted peritoneal space, and an incomplete cytoreduction reduced drug clearance.
  
  
  CONCLUSIONS
  Surgical and clinical factors may require modifications of chemotherapy administration. A large visceral resection and a contracted peritoneal space caused a reduced doxorubicin clearance. Total diffusion surface is an important determinant of doxorubicin pharmacokinetics.
authors.affiliation: Washington Cancer Institute, Washington Hospital Center, 106 Irving Street, NW, Suite 3900, Washington, DC 20010, USA. Paul.Sugarbaker@medstar.net
authors.forename: P H
authors.initials: PH
authors.lastname: Sugarbaker
authors.forename: K
authors.initials: K
authors.lastname: Van der Speeten
authors.forename: O
authors.initials: O
authors.lastname: Anthony Stuart
authors.forename: D
authors.initials: D
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001063:Appendiceal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D002277:Carcinoma / Q000188:drug therapy* / Q000601:surgery; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy / Q000379:methods; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D007274:Injections, Intraperitoneal; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin