title: Hyperthermic intraoperative intraperitoneal chemotherapy with cisplatin and doxorubicin in patients who undergo cytoreductive surgery for peritoneal carcinomatosis and sarcomatosis: phase I study.
abstract: BACKGROUND
  Hyperthermic intraperitoneal intraoperative chemotherapy (HIIC) combined with cytoreductive surgery (CS) has been proposed as a new multimodal treatment mainly for carcinomatosis of gastrointestinal origin. To evaluate whether this regimen could be used for other tumor types, the authors conducted a Phase I study on HIIC with doxorubicin and cisplatin in patients with peritoneal carcinomatosis or sarcomatosis.
  
  
  METHODS
  Thirty-one patients with peritoneal carcinomatosis or sarcomatosis (PCS) were enrolled for the study. After completion of CS, HIIC was administered with drug doses that were increased for each consecutive cohort following a three-patient cohort scheme. Thereafter, the accrual was stopped when Grade 4 locoregional or systemic toxicity was observed. The maximum tolerated dose (MTD) was considered the dose in the previous triplet. Drug pharmacokinetics and procedure costs also were analyzed.
  
  
  RESULTS
  After CS, residual tumors were not present or measured less than or equal to 3 mm (in dimension) in all cases. Maximum tolerated dose was 15.25 and 43.00 mg L(-1) for doxorubicin and cisplatin, respectively. The perfusate/plasma area under the curve ratios were favorable for both drugs, at 162+/-113 and 20.6+/-6.0, respectively, for doxorubicin and cisplatin. Doxorubicin levels in the peritoneum were higher than in tumor or normal tissue samples. There were no postoperative deaths. Surgery-related complications were observed in 25% of cases. Findings at cost analysis showed that the length of stay in the operation room and intensive care unit were the major cost drivers.
  
  
  CONCLUSIONS
  Cytoreductive surgery combined with HIIC is an expensive but feasible therapeutic approach for locally advanced abdominal tumors. Because our preliminary findings for local disease control are encouraging, a Phase II study is now advisable to verify the activity of this promising treatment.
authors.affiliation: Dipartimento di Scienze Oncologiche e Chirurgiche, Sezione Clinica Chirurgica Generale II, Universita' di Padova, Italy. carlor.rossi@unipd.it
authors.forename: Carlo R
authors.initials: CR
authors.lastname: Rossi
authors.forename: Mirto
authors.initials: M
authors.lastname: Foletto
authors.forename: Simone
authors.initials: S
authors.lastname: Mocellin
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Pilati
authors.forename: Simone Michele
authors.initials: SM
authors.lastname: De
authors.forename: Marcello
authors.initials: M
authors.lastname: Deraco
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavaliere
authors.forename: Pietro
authors.initials: P
authors.lastname: Palatini
authors.forename: Fabiola
authors.initials: F
authors.lastname: Guasti
authors.forename: Romano
authors.initials: R
authors.lastname: Scalerta
authors.forename: Mario
authors.initials: M
authors.lastname: Lise
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000191:economics / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003365:Costs and Cost Analysis; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007263:Infusions, Parenteral; D007430:Intraoperative Care; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000191:economics / Q000628:therapy*; D012509:Sarcoma / Q000191:economics / Q000601:surgery / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D002945:Cisplatin