ABSTRACT
BACKGROUND: Irinotecan, when combined with cisplatin, is an effective treatment for advanced non-small cell lung cancer (NSCLC). This constitutes a rationale for conducting a phase I study of chemoradiotherapy including this combination for locally advanced NSCLC. PATIENTS AND METHODS: Patients with locally advanced NSCLC and a performance status of 0 or 1 were eligible. The protocol consisted of escalating doses of irinotecan on days 1 and 15, and daily low-dose cisplatin (6 mg/m(2) daily for a total dose of 120 mg/m(2)) combined with concurrent hyperfractionated accelerated thoracic irradiation (1.5 Gy twice daily for a total dose of 60 Gy). RESULTS: The maximum tolerable dose was 50 mg/m(2) of irinotecan, and the dose-limiting toxicity was esophagitis. Tumor response was observed in 50% of cases, and the median survival time of the 12 patients enrolled was 10.1 months, including two patients with 5-year disease-free survival. A pharmacokinetics study demonstrated an accumulation of total platinum, but not of free platinum, during the 26-day treatment period. CONCLUSION: The recommended dose for phase II studies was determined.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Camptothecin/pharmacokinetics , Carcinoma, Non-Small-Cell Lung/mortality , Cisplatin/administration & dosage , Combined Modality Therapy , Dose Fractionation, Radiation , Esophagitis/etiology , Female , Humans , Irinotecan , Lung Neoplasms/mortality , Male , Maximum Tolerated Dose , Middle Aged , Survival RateABSTRACT
BACKGROUND: Hepatocyte growth factor (HGF) is a growth factor with multiple biologic properties, including mitogenic, morphogenic, anti-apoptotic, and antifibrogenic activities. Long-term administration of the deletion variant of HGF (dHGF) might contribute to the prevention of chronic liver allograft dysfunction, which is attributed to immunologic and nonimmunologic reactions. METHODS: Low-dose tacrolimus was administered to rat-liver recipients after transplantation. Effects of dHGF on transplanted livers treated with low-dose tacrolimus were investigated. RESULTS: Rats receiving liver transplants treated with only low-dose tacrolimus administration showed chronic allograft dysfunction. Treatment with dHGF prolonged the survival time of rats that received liver allografts and suppressed fibrosis of liver allograft. Treatment with dHGF also suppressed the expression levels of interleukin (IL)-1beta, caspase-1, and transforming growth factor (TGF)-beta mRNAs in liver allografts. CONCLUSIONS: The findings indicate that dHGF may prevent chronic liver-allograft dysfunction and thus may become a novel treatment for chronic liver-allograft dysfunction.
Subject(s)
Graft Survival/drug effects , Hepatocyte Growth Factor/pharmacology , Liver Transplantation , Liver/physiology , Animals , Apoptosis/physiology , Caspase 1/genetics , Chronic Disease , Gene Expression/immunology , Graft Survival/immunology , Interleukin-1/genetics , Liver/drug effects , Liver/surgery , Male , RNA, Messenger/analysis , Rats , Rats, Inbred Lew , Transforming Growth Factor beta/genetics , Transplantation, HomologousABSTRACT
BACKGROUND: Although radical operation and adjuvant chemoradiotherapy improve survival in patients with advanced esophageal cancer, more than half of these patients have recurrence. The aim of this study was to explore treatment responses and prognostic factors in patients with recurrent esophageal cancer. METHODS: The operative specimens from 258 patients undergoing radical esophagectomy with extended lymphadenectomy for esophageal squamous cell carcinoma between 1990 and 1999 were analyzed. Depth of tumor invasion, and the extent and location of lymph node metastases were determined. Postoperative recurrence was identified from positive findings on successive 3-month examinations of tumor markers, 6-month examinations of ultrasonography, and annual computed tomography. Of 258 patients, 95 had recurrence by the end of 2000 (mean follow-up was 22 months, range, 2-113). Of those 95 patients, 76 received nonsurgical treatment, 7 received operative intervention, and 12 received no treatment. Clinicopathologic features of recurrent tumors were analyzed to determine prognostic values. Serum anti-p53 antibodies (S-p53-Abs), serum C-reactive protein concentration (S-CRP), and albumin concentration were also analyzed. RESULTS: The main recurrent patterns were nodal (n = 45) and organ (n = 35). Of the nonsurgical treatment group, 47 patients received chemoradiotherapy; 17, chemotherapy; and 12, radiotherapy. Overall clinical response was observed in 26 of 76 patients (34%). Treatment response was significantly associated with the type of recurrence, history of perioperative adjuvant therapy, time of recurrence, number of recurrent tumors, albumin concentration, S-CRP, and S-p53-Abs. Multivariate analysis suggested that S-p53-Abs and S-CRP were independent prognostic factors. CONCLUSION: The status of S-p53-Abs and S-CRP may predict response and outcome of patients with recurrence of esophageal cancer after radical operation.
