Dual anti-cancer effects of weekly intraperitoneal docetaxel in treatment of advanced gastric cancer patients with peritoneal carcinomatosis: a feasibility and pharmacokinetic study.
This study evaluated the feasibility and pharmacology of intraperitoneal docetaxel (IP docetaxel) when administered weekly for 3 consecutive weeks, followed by 1 week without treatment. A total of 24 patients with peritoneal carcinomatosis of gastric cancer (10 preoperative, 7 postoperative and 7 recurrent) were enrolled in this study. Docetaxel was dissolved in an isotonic saline to a final 1 liter solution and was administered in a 1 h dosage of 25, 35, 45 and 60 mg/m(2) to determine the maximum tolerated dose (MTD). To measure the docetaxel concentration, blood and peritoneal fluid samples were collected 0.5, 1, 2, 3, 6 and 24 h after administering the drug to 15 patients. A total of 109 chemotherapy cycles were administered, with a median of four cycles per patient (range 2-9). The MTD of the weekly IP docetaxel was defined at 60 mg/m(2). At a docetaxel dosage of 60 mg/m(2) per week, the dose-limiting events of grade 3 abdominal pain and grade 3 diarrhea, which may be associated with local toxicity, occurred. Peak concentrations of peritoneal fluid ranged from 24.5 to 68.7 microg/ml. The mean ratio of the area under concentration (AUC) in the peritoneal fluid to the plasma concentration was 515. Furthermore, the mean of plasma AUC by IP docetaxel was 5.63 microg h/ml versus that of IV docetaxel at a dose of 60 mg/m(2). The response rate of the preoperative IP docetaxel was 80% (4 CR, 4 PR, 1 NC and 1 PD), which was judged with laparoscopy and peritoneal lavage cytology. Gastrectomy, with D2 lymph node dissection, was performed on all of the patients evaluated as CR. The weekly IP docetaxel demonstrated a low toxicity and high efficacy for peritoneal carcinomatosis with dual anti-cancer effects via the peritoneal surface and capillary blood supply due to its unique pharmacokinetic property.
Fushida
Sachio
S
Department of Gastroenterologic Surgery, Kanazawa University Hospital, Kanazawa 920-8641, Japan. fushida@surg2.m.kanazawa-u.ac.jp
Kinoshita
Jun
J
Yagi
Yasumichi
Y
Funaki
Hiroshi
H
Kinami
Shinichi
S
Ninomiya
Itasu
I
Fujimura
Takashi
T
Nishimura
Genichi
G
Kayahara
Masato
M
Ohta
Tetsuo
T
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002196:Capillaries / Q000378:metabolism; D000077143:Docetaxel; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007700:Kinetics; D008207:Lymphatic Metastasis; D008297:Male; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D012008:Recurrence; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel