Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Dual anti-cancer effects of weekly intraperitoneal docetaxel in treatment of advanced gastric cancer patients with peritoneal carcinomatosis: a feasibility and pharmacokinetic study. 1842 92

Gastric cancer is the fourth most common type of cancer globally and accounts for the second highest cancer-associated mortality rate in the world. Current treatment strategies for gastric cancer include surgery, radiotherapy, chemotherapy and targeted therapy. Intraperitoneal (IP) chemotherapy may increase the IP concentrations of chemotherapy drugs and reduce the systemic toxicity. At present, IP chemotherapy is used to treat patients with advanced gastric cancer, which has a high rate of peritoneal recurrence. The present study evaluated the feasibility of using docetaxel, cisplatin and fluorouracil (DCF) in an IP and intravenous (IV) dual chemotherapy regimen for the treatment of advanced gastric cancer. The treatment-associated adverse reactions and preliminary efficacy were reported. The first dose level utilized the full dose of DCF: Docetaxel, day one, 45 mg/m2 (IP) and day eight, 30 mg/m2 (IV); cisplatin (DDP), day one, 75 mg/m2 (IP); and fluorouracil (FU), days one to five, 750 mg/m2 (continuous IV). A total of six patients were treated at this level and two patients withdrew due to serious adverse reactions. Taking into account that the the tolerated doses used in combination regimens for Eastern populations are lower than that of the corresponding doses for Western populations, the dosages of the three drugs were all reduced by 20% in the application of the second dose level: Docetaxel, day one, 30 mg/m2 (IP) and day eight, 30 mg/m2 (IV); DDP, day two, 60 mg/m2 (IP); and FU, days one to five, 600 mg/m2 (continuous IV). A total of 26 patients were treated at this level. The main adverse reaction was bone marrow suppression, with grade III/IV neutropenia, leukopenia and febrile neutropenia accounting for 61.5, 53.8 and 19.2% of reactions, respectively, and grade III/IV anemia and thrombocytopenia accounting for 19.2 and 15.4% of reactions, respectively. Gastrointestinal adverse reactions primarily consisted of abdominal pain, with grade III/IV abdominal pain accounting for 30.8% of reactions. Only 7.7% of the patients withdrew from the treatment. The median time to progression (TTP) was five months [95% confidence interval (CI), 1.0-9.0 months], and the median overall survival (OS) was nine months (95% CI, 7.4-10.6 months). It was concluded that the DCF regimen with reduced dosage should be applied. IP and IV dual chemotherapy for the treatment of unresectable advanced gastric cancer is tolerated and demonstrated a good initial efficacy. Strategies for mitigating and reducing the adverse gastrointestinal reactions, particularly abdominal pain, may be the focus of future studies.
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PMID:DCF intraperitoneal and intravenous dual chemotherapy regimen for advanced gastric cancer: A feasibility study. 2543 15