Trofosfamide in patients with pancreatic cancer.

BACKGROUND: In a previous phase II trial of ifosfamide (IFO) several patients with pancreatic cancer responded to therapy (1). Trofosfamide (TROFO) is an orally taken oxazaphosphorine prodrug. Metabolic products of TROFO include ifosfamide (IFO) and cyclophosphamide (CYCLO). In clinical pilot studies with TROFO against refractory malignancies mild toxicity was reported. PATIENTS AND METHODS: Since virtually all patients with advanced pancreatic cancer are symtomatic, we designed and conducted a prospective phase II trial to evaluate the activity of single agent therapy with TROFO given orally continuously (three times 50 mg daily), and to assess the toxicity, duration of remission, and overall survival of the treated patients. RESULTS: 16 patients were enrolled onto the study. In one patient a PR has been observed; the mayor response rate was 6%. The mayor toxicity was bone marrow toxicity with granulocytopenia (WHO grade II) and anemia (WHO grade II) in virtually all patients. CONCLUSION: Single agent therapy with TROFO in patients with pancreatic cancer is safe and well tolerated; however, it shows low clinical activity.

[In vitro studies of pancreatic enzyme substitution]. / In-vitro-Untersuchungen zur Pankreasenzymsubstitution.

In-vitro activity of 14 commercial pancreatin preparations, commonly used in the Federal Republic of Germany, were tested. All had been declared by their manufacturers to contain more than 6000 FIP (Fédération International Pharmaceutique) units of lipase and to be acid resistant. The declared lipase and amylase amounts were found to be present in 11 of the 14 preparations. Three of the 14 preparations, said to be acid resistant were found not to be so in buffer with falling pH values between 4.0 and 2.5, so that there occurred an, at times marked, loss of enzyme activity. Most noticeable was the poor solubility of most preparations at pH 6.6. Only three of the 14 liberated their total enzyme content within 60 minutes, as they should for theoretical reasons, based on the relatively short duodeno-cecal transit time.

[Pancreatic secretion in domestic sprue]. / Pankreassekretion bei einheimischer Sprue.

Pancreatic function was determined (using the secretin-pancreozymin test) before the use of gluten-free diet in 22 patients with endemic (celiac) sprue. Water and bicarbonate secretion were within normal limits, if anything there was a trend to high-normal values. Remarkable and apparently characteristic for celiac sprue was the only slight contraction of the gallbladder after intravenous injection of submaximal doses of cholecystokinin-pancreozymin (CCK). Secretion of the 3 enzymes amylase, lipase and trypsin was decreased in about one third of cases, the difference relating both to the concentrations and the amount secreted, compared with normal control values was significant (P greater than 0.01). But in no case was the reduced enzyme secretion so marked that one would expect maldigestion. Multivariate non-linear discriminance analysis demonstrated that pancreatic secretion in sprue is quite distinct from that in healthy subjects and those with chronic pancreatitis. It is assumed that there is a pattern of exocrine pancreatic secretion typical for sprue.

[Does alcohol enhance the toxicity of paraquat (author's transl)]. / Verstärkt Alkohol die Toxizität von Paraquat?

Oral ingestion of about 80 ml of a 20% solution of paraquat (Gramoxone) by a 44 years-old male alcoholic was followed by an acute edema of the lungs and death within 24 hrs. The administration of corticosteroids as well as the employment of forced diuresis, charcoal hemoperfusion and hemodialysis did not prevent this acute lethal outcome. The very high initial plasma concentration of 2.56 mg/l dropped quickly after hemoperfusion and dialysis to 1.19 mg/l. In mice ingesting a 5% ethanol solution for one week the LD50 of paraquat was diminished to 80 (63 - 102) mg/kg p.o. as compared to 170 (126 - 229) mg/kg p.o. in controls indicating that alcohol is able to enhance the acute toxicity of paraquat.