Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: I. A randomized dose escalation and feasibility study with bi- and tri-weekly regimens.

BACKGROUND: To determine the maximum tolerated dose of a bi- and tri-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone plus etoposide (CHOEP) regimen without stem-cell support. PATIENTS AND METHODS: Randomized phase I/II multicenter four-level (cyclophosphamide: 1000-1200-1400-1600 mg/m2; doxorubicin: 55-60-65-70 mg/m2; etoposide: 375-450-525-600 mg/m2) dose escalation study with CHOEP-14 and CHOEP-21 in young patients (18-60 years) with newly diagnosed aggressive non-Hodgkin's lymphoma. Dose-limiting toxicity was defined as thrombocytopenia <80,000/mm3 and leukocytopenia <2500/mm3 on days 16 (CHOEP-14) and 23 (CHOEP-21) or prolonged (>4 days) leukocytopenia (<1000/mm3) or thrombocytopenia (<20,000/mm3). RESULTS: One hundred and thirty-nine patients (high-CHOEP-14: 47, high-CHOEP-21: 92) were randomly allocated to the study. Maximal tolerated dose was level 2 for CHOEP-14 and level 4 for CHOEP-21. With a less favorable profile of patients in CHOEP-14, 4-year event-free survival was 47.9% after high-CHOEP-14 and 66.2% after high-CHOEP-21, 4-year overall survival 62.1% after high-CHOEP-14 and 73.4% after high-CHOEP-21, respectively. CONCLUSION: Significant dose escalations of CHOEP are possible with granulocyte colony-stimulating factor support, with different chemotherapy models favoring the maximally escalated bi- or tri-weekly regimen, respectively. Because a higher total dose can be achieved with six cycles of the tri-weekly compared with the biweekly regimen, CHOEP-21 at dose escalation level 3 was chosen for a nationwide randomized comparison with baseline CHOEP-21 in a subsequent phase III trial.

Torsades de pointes caused by Mibefradil.

We report a case of symptomatic Torsades de pointes due to QTc prolongation by Mibefradil, which potentially explains unexpected deaths related to this drug. Multiple episodes of Torsades de pointes were documented in a 76-year-old woman with significant QTc prolongation of 0.53 s. After discontinuation of Mibefradil QTc intervals normalized and no further ventricular tachyarrythmias were observed. We conclude that Mibefradil can cause QTc prolongation and life threatening ventricular dysrhythmias.

Photodynamic therapy of nonresectable cholangiocarcinoma.

BACKGROUND & AIMS: Successful treatment in nonresectable Bismuth type III and IV cholangiocarcinoma is seldom achieved. The aim of this study was to evaluate the effect of photodynamic therapy on cholestasis, quality of life, and survival in these patients. METHODS: Nine patients with advanced nonresectable cholangiocarcinomas Bismuth type III and IV, who showed no sufficient drainage (bilirubin decrease <50%) after endoscopic stent insertion, underwent photodynamic therapy. Two days after intravenous application of a hematoporphyrin derivate, intraluminal photoactivation was performed cholangioscopically. Serum bilirubin, quality of life, and survival time were assessed in two monthly intervals after photodynamic therapy. RESULTS: After photodynamic therapy, bilirubin serum levels declined from 318 +/- 72 to 103 +/- 35 micromol/L (P = 0.0039) with no significant increase during the two monthly follow-ups. Quality of life indices improved dramatically and remained stable (e.g., Karnofsky index from 32.2% +/- 8.13% to 68.9% +/- 6.1%; P = 0.0078). Thirty-day mortality was 0%, and median survival time was 439 days. CONCLUSIONS: This study provides clear evidence that photodynamic therapy is effective in restoring biliary drainage and improving quality of life in patients with nonresectable disseminated cholangiocarcinomas Bismuth type III and IV. Compared with published data, survival time seems to be prolonged.

[Causes of death and some etiologic aspects of acute and chronic pancreatitis]. / Zu Todesursachen und einigen ätiologischen Aspekten der akuten und chronischen Pankreatitis.

The study gives a survey of the causes of death of 106 patients suffering from acute pancreatitis and of 125 chronic pancreatitis cases. They account for 1.41% and 1.69% respectively of the autopsies performed by us. In 76.4% of the 106 cases of acute pancreatitis the disease was the main cause directly responsible for the death. Chronic pancreatitis was the main underlying disease or a significant secondary condition in the chronic group. The results of etiologic analysis are in acute pancreatitis: 67.9% biliary tract changes, 7.5% alcohol abuses and 20.8% postoperative damages. Alcoholism (44 cases) was important by patients with chronic pancreatitis.