[Value of sonographic diagnosis in retroperitoneal teratoma in adults]. / Zum Stellenwert der sonographischen Diagnostik beim retroperitonalen Teratom des Erwachsenen.

A 56-year old man was admitted with a tumour-like lesion located in the retroperitoneal space with adherence to the left adrenal gland. An extensive diagnostic procedure could neither establish the diagnosis nor differentiate the lesion from the adrenal gland. After tumour biopsy by ultrasound surgery was recommended and performed and the final diagnosis--mature teratoma--was established. In this article we discuss the genesis and therapeutic possibilities of mature teratoma in adults.

Tolerance, safety, and kinetics of the new antineoplastic compound dexniguldipine-HCl after oral administration: a phase I dose-escalation trial.

Dexniguldipine-HCl is a new dihydropyridine compound that exerts selective antiproliferative activity in a variety of tumor models and, in addition, has a high potency in overcoming multidrug resistance. The purpose of this trial was to determine the toxicity and pharmacokinetics of dexniguldipine and to establish a recommended dose for phase II trials. A total of 37 patients with cancer were treated with oral dexniguldipine in increasing doses for up to 7 days. The main parameters evaluated were subjective tolerance and laboratory and cardiovascular parameters (blood pressure and ECG). Blood samples were drawn for analysis of the drug's pharmacokinetics. Dizziness and nausea were the major adverse events observed in seven patients, but episodes were generally mild and not clearly dose-related. Vomiting occurred in one patient. Hypotensive effects and orthostatic dysregulation were observed in some patients but were not considered to be dose-limiting. Therefore, no dose-limiting toxicity was found and the maximally tolerable dose could not be determined. Pharmacokinetic data showed wide interindividual variation and a dose-dependent increase in steady-state serum concentrations at doses of up to 1,000 mg daily, with no clear further increase being observed at higher doses. Consistently high concentrations were achieved with the 2,500-mg dose. Despite the lack of dose-limiting toxicity, higher doses of dexniguldipine do not appear to be useful for clinical evaluation because of the pharmacokinetic properties of the compound: therefore, 2,500 mg/day is recommended as the daily dose for phase II trials.

A phase I trial of interferon alpha-2b with folinic acid and 5-fluorouracil administered by 4-hour infusion in metastatic colorectal carcinoma.

Preclinical data suggest that both folinic acid and interferon may enhance the efficacy of 5-fluorouracil (5-FU) in colorectal carcinoma. We therefore initiated a phase I trial evaluating the doses, safety, and pharmacokinetics of the combination of recombinant interferon (IFN) alpha-2b with folinic acid (FA) and 5-FU. Seventeen patients with colorectal cancer who failed local chemotherapy received 5-FU as a 4-hour infusion, preceded by a bolus of FA and IFN. The 5-FU dose was escalated over the range of 400 to 650 mg/m2/d for a period of 7 days. Folinic acid was administered as a bolus in a fixed dose of 200 mg/m2/d and IFN as 5 million U/d subcutaneously on days 1 to 7. A total of 89 courses of therapy were completed for the 17 patients, of which there were 10 paired courses with a combination of 5-FU and IFN or 5-FU alone, being performed to analyze the pharmacokinetics and modulation of 5-FU by IFN. The maximum tolerated dose of 5-FU using this combination and a 4-hour schedule was 600 mg/m2/d for 7 days. The dose-limiting toxicity of this regimen was diarrhea. Mucositis and myelosuppression was not a marked problem at dose levels of 400 and 500 mg/m2/d for 7 days. However, at a dose level of 600 to 650 mg/m2/d for 7 days, grade 3 and 4 (WHO) leukopenia occurred in 50% and mucositis occurred in 33%. At a given dose of 5 million U, IFN did not significantly influence 5-FU serum levels. Mean steady-state serum levels of 5-FU at 500 mg/m2 given as a 4-hour infusion were 16.55 +/- 9.34 mumol/L and 18.23 +/- 12.77 mumol/L with and without IFN, respectively. Mean area under the curve (mumol/L x min) was 4,008 +/- 2,133 and 5,114 +/- 2,567 with and without interferon, respectively. Objective responses were seen in one of 17 of these heavily pretreated patients and stable disease was seen in seven of 17 patients. The recommended dose of 5-FU for use of phase II studies is 500 mg/m2/d for 7 days. We conclude that the toxicity of 5-FU plus FA with and without IFN alpha-2b can be reduced by using a 4-hour infusion instead of a bolus.

A phase II trial of interferon alpha-2b with folinic acid and 5-fluorouracil administered by 4-hour infusion in metastatic colorectal carcinoma.

Preclinical data suggest that folinic acid as well as interferon alpha-2b may enhance the antitumor activity of 5-fluorouracil (5-FU). In a phase I trial, we recently showed that interferon alpha-2b (IFN), folinic acid and 5-FU can be safely administered with a 4-hour infusion of 5-FU. We therefore initiated a phase II trial evaluating the efficacy and safety of these three drugs. Forty-five evaluable patients with advanced metastatic colorectal cancer, documented progressive disease, and previously unexposed to chemotherapy were treated with sequential IFN 5 MU/d subcutaneously and folinic acid 200 mg/m2/d as bolus on days 1 to 7 followed by 5-FU in a 4-hour infusion at a dose of 500 mg/m2/d, resulting in a total dose of 3,500 mg/m2/course. This schedule was repeated on day 21. A total of 204 courses of therapy were completed. One of 45 patients (2%) achieved a complete response, and 13 of 45 patients (29%) achieved a partial response. An additional 16 patients (36%) had stable disease. The median time to disease progression was seven months (2 to 24 months). Despite the relatively high-dose intensity of 5-FU, toxicity was very mild. Grade 3 or 4 myelosuppression, stomatitis, and nausea/vomiting occurred in only three of 45 patients (7%). Four of 45 patients (9%) suffered from severe (grade 3/4) diarrhea. Neurotoxicity and infections of grade 2 to 4 did not occur. From these data we conclude that modulation of 5-FU with both folinic acid and IFN induces an overall response rate of 31% in disseminated colorectal cancer. Using a 4-hour application schedule of 5-FU, the therapeutic index can be improved even for high-dose intensity and requires further evaluation in combination with other modulators.