Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluorouracil (5-FU) and cisplatin display marked therapeutic synergy in preclinical models and are effective in the treatment of a number of solid tumors when combined and administered intravenously (IV). Each drug has also been administered intraperitoneally (IP) and displays a favorable pharmacologic profile and acceptable clinical toxicity. We therefore undertook a phase I study to determine the feasibility and toxicity of combination IP chemotherapy with these agents. Thirty-one patients with histologically documented malignancy confined to the peritoneal space were treated with cisplatin 90 mg/m2 mixed with 5-FU in 2 L of lactated Ringer's solution and given IP for 4 hours every 28 days. Cohorts of at least three patients received starting 5-FU concentrations ranging from 5 mmol/L (1,300 mg in 2 L) to 20 mmol/L. The dose-limiting toxicity was neutropenia with a median granulocyte nadir of 156 cells per microliter occurring at a 5-FU dose of 20 mmol/L. Intrapatient escalation of the 5-FU dose was permitted and 15 cycles of chemotherapy were delivered at 5-FU concentrations greater than 20 mmol/L, the highest concentration being 30.7 mmol/L (8 g of 5-FU in 2L). Other toxicities included mild to moderate nausea during all cycles of therapy, vomiting in 54% of cycles, and diarrhea in 15% of cycles. Abdominal pain, renal dysfunction, peripheral neuropathy, and oral mucositis occurred infrequently and were not related to the 5-FU dose. Peritoneal fluid and plasma 5-FU concentrations were measured by high-performance liquid chromatography (HPLC) in selected patients. Mean peak plasma 5-FU concentrations ranged from 6.19 mumol/L to greater than 60 mumol/L, and peritoneal fluid to plasma 5-FU area under the curve (AUC) ratios ranged from 85 to 1,150. Nine of 15 patients with nonbulky disease had resolution of malignant ascites or at least a 50% reduction of peritoneal studding by tumor at repeat laparotomy. We conclude that combination IP chemotherapy with cisplatin and 5-FU is technically feasible and has acceptable clinical toxicity and a favorable pharmacologic profile. The recommended starting 5-FU dose for phase II trials is 3,900 mg mixed with 90 mg/m2 of cisplatin in 2 L of isotonic fluid.
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PMID:Phase I clinical and pharmacologic study of intraperitoneal cisplatin and fluorouracil in patients with advanced intraabdominal cancer. 223 Aug 97

No satisfactory treatment exists to treat or prevent malignant ascites secondary to nonovarian intraperitoneal (IP) disseminated malignancies. A Phase I/II clinical trial combining radical cytoreductive surgery (CS) and IP hyperthermic chemotherapy (IPHC) with mitomycin C is presented. Between December 9, 1992 and July 31, 1995, 39 patients (pts) were explored for IP cancer. Five pts with known liver metastases were excluded, leaving 34 pts (15 female, 19 male) of median age 53 (range, 17-76). The majority of pts had disseminated IP cancers of gastrointestinal origin (80%). Prior therapy included the following: chemotherapy, 20 pts (59%); surgery, 29 pts (85%); and radiation, 2 pts (6%). Following CS, IPHC with mitomycin C was done. At surgery, 12 pts (35.3%) had frank ascites, and 12 pts (35.3%) had positive IP cytology without ascites. The median hospital stay was 9 days (range, 5-65) with no 30-day mortality. Complications for 36 treatments included: thrombocytopenia Eastern Cooperative Oncology Group grade 3 or 4, two cases (5.6%); neutropenia requiring granulocyte colony-stimulating factor, seven cases (19.4%); sepsis, four cases (11.1%); bowel leak, two cases (5.6%); and serous wound leak, two cases (5.6%). Ascites correlated with worse resection status (P = 0.025). Ascites was controlled in 9 of 12 (75.0%) pts, with failures at 1, 4, and 14 months (median follow-up, 7.5 months). No cytology-positive ascites-negative pts developed clinical ascites (median follow-up, 9.4 months). The median survival time in pts with ascites was 10.1 months versus 32.7 for patients without ascites (P = 0.013). For the entire study population, the 1- and 2-year survival rates were 74.6 and 48.5 per cent, respectively (median follow-up, 18.2 months). In this study, malignant ascites was controlled in 75 per cent of cases and prevented in all pts with positive IP cytology. CS plus IPHC appears to be relatively well tolerated and may be effective for the treatment and prevention of malignant ascites.
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PMID:Treatment and prevention of malignant ascites associated with disseminated intraperitoneal malignancies by aggressive combined-modality therapy. 901 27

A 54-year-old woman with scirrhous gastric cancer in the upper third area was admitted to our hospital. She was diagnosed with advanced gastric cancer that was inoperable due to peritoneal metastasis, so weekly paclitaxel (PTX) therapy was carried out. After 2 courses, malignant ascites completely disappeared and bilateral hydronephrosis improved. After 4 courses, no ascites or hydronephrosis were seen. Only neutropenia (grade 2) and alopecia (grade 1) were observed as adverse events during the therapy, but no major adverse events were noted. We also investigated the concentration of paclitaxel in ascites. Two hours after intravenous injection of PTX, the concentration of PTX in ascites rose over the reported cytotoxic dose of PTX, and this available concentration was maintained after 48 hours. Weekly paclitaxel therapy is suggested to be one of the safe and useful treatments for advanced gastric cancer with malignant ascites.
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PMID:[A case of advanced gastric cancer with malignant ascites responding to weekly paclitaxel therapy]. 1710 15