title: Intraperitoneal paclitaxel: a possible impact of regional delivery for prevention of peritoneal carcinomatosis in patients with gastric carcinoma.
abstract: OBJECTIVE
  Peritoneal carcinomatosis is a common pattern of failure among gastric cancer patients. Adequate postoperative adjuvant chemotherapy could reduce the risk of this lethal recurrence.
  
  
  METHODS
  Intraperitoneal (IP) paclitaxel, a useful option for treatment of ovarian cancer, was tested in a phase I trial involving gastric carcinoma patients. The eligibility criteria included confirmed gastric carcinoma patients with uncontrollable ascites, Eastern Cooperative Oncology Group performance status < or = 2, adequate major organ functions, and clinical disease progression following prior treatment(s) with oral or intravenous anticancer drugs. The starting dose (Level 1) was 60 mg/m2 weekly for 3 weeks followed by a week of rest, and the treatment was to be continued for at least 2 cycles unless unacceptable toxicity occurred. Peritoneal and plasma samples were obtained 0 hour, 3 hours, 24 hours, and one week after the end of drug instillation for pharmacokinetic analysis
  
  
  RESULTS
  Of 4 patients enrolled, 3 were eligible and evaluable for toxicity. Three of the 4 patients failed to receive two cycles of treatment chiefly because of failure in the drug delivery, resulting in termination of the trial in the current form. Peak IP/plasma ratio of > 2000 was obtained at 3 hours after administration. Half-life of the drug ranged from 17.4 to 65.3 hours. Ascites diminished in 2 of 3 patients during the course of the treatment.
  
  
  CONCLUSIONS
  High intraperitoneal concentration was maintained following IP administration at 60 mg/m2. IP paclitaxel could be a promising component of radical or prophylactic treatment for the peritoneal disease when combined with concurrent or sequential systemic administration of other anticancer drugs.
authors.affiliation: Department of Surgery II, Nagoya University School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8580, Japan. ykodera@med.nagoya-u.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ito
authors.forename: Seiji
authors.initials: S
authors.lastname: Ito
authors.forename: Norifumi
authors.initials: N
authors.lastname: Ohashi
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yamamura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koike
authors.forename: Michitaka
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Hayao
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002277:Carcinoma / Q000517:prevention & control* / Q000556:secondary; D006801:Humans; D007263:Infusions, Parenteral; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D010534:Peritoneal Neoplasms / Q000517:prevention & control* / Q000556:secondary; D013274:Stomach Neoplasms / Q000473:pathology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel