ABSTRACT
A phase II study was carried out to evaluate the efficacy and toxicity of a double biochemical modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and leucovorin (LV) in patients with advanced unresectable colorectal cancer. Forty-two patients with measurable metastases of colorectal cancer were treated with 5-FU in daily doses of 600 mg/m2 given in a 6-hour intravenous (i.v.) infusion on days 1-5, LV 50 mg/m2 i.v. on days 2,3 and 5, and MTX 40 mg/m2 i.v. on days 1 and 4, every 4 weeks. Twenty-eight patients had a single metastatic site, eleven double, whereas three had more than two metastatic sites. Objective response (one complete response) was observed in 12 of 40 patients (30%) (95% confidence interval 16-48), stable disease in 19 patients (47%) and progression in 9 patients (23%). Overall median survival was 12 months. Median time to progression was 6 months. Treatment was generally well tolerated. The most frequent adverse reactions were stomatitis (38%), nausea and vomiting (35%), diarrhea (31%), leukopenia (18%), and plantar-palmar erythroderma (15%). The combination of 5-FU, LV and MTX seems to be an active regimen in advanced colorectal cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/pathology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Infusions, Intravenous , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Neoplasm Metastasis , Survival AnalysisABSTRACT
BACKGROUND: Serum cystatin C, a cysteine protease inhibitor, has been suggested as a new marker of glomerular filtration rate (GFR). This study explored the possibility of replacing the creatinine clearance (CrCl) estimation of GFR with cystatin C in early detection of renal impairment in cancer patients on chemotherapy. METHODS: Serum creatinine and cystatin C concentrations as well as 24-h CrCl were determined simultaneously in 72 cancer patients. Among them, 60 were treated with combined chemotherapy with cisplatin (CDDP). Creatinine was determined enzymatically with a spectrophotometric method. Serum cystatin C was determined by a particle-enhanced turbidimetric immunoassay. RESULTS: Cystatin C and creatinine correlated significantly (P = 0.001) with CrCl. The correlation was significantly better for cystatin C than creatinine (r = 0.84 vs 0.74; P = 0.01). Stepwise regression analysis identified no differences for the correlations between cystatin C and CrCl in patients with or without metastases (r = 0.82 and 0.84, respectively) as well as before treatment and before the fourth cycle of chemotherapy (r = 0.70 and 0.75, respectively). A cystatin C cutoff concentration of 1.33 mg/L had 87% sensitivity and 100% specificity for detecting CrCl <78 mL/min. ROC analysis indicated that cystatin C was superior to serum creatinine for predicting CrCl <78 mL/min (P <0.04). CONCLUSIONS: Serum cystatin C is superior to serum creatinine for detection of decreased CrCl and potentially for the estimation of GFR in cancer patients independent of the presence of metastases or chemotherapy.
