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Pancreatic cancer is resistant to most chemotherapeutic regimens. Based upon evidence of synergy between 5-fluorouracil (5-FU) and cisplatin (CDDP), and of enhanced 5-FU activity in the presence of leucovorin in other neoplasms, a phase II study of CDDP, 5-FU, and leucovorin was conducted to determine the efficacy of this regimen in patients with unresectable adenocarcinomas of the pancreas. Nineteen patients were enrolled, and all were evaluable for toxicity and response. One complete and two partial responses were observed (15.8%). Adverse effects were reversible and tolerable. This regimen has limited activity against pancreatic cancer, and cannot be recommended as standard therapy in this disease.

Male and female C57BL/10J mice were fed 0 or 800 ppm cyproterone acetate (CPA) in the diet for 13 weeks. 1. Body weight was reduced (P0.001 at 13 weeks) by approximately 33%. 2. Seminal vesicle weights were reduced (P0.001) and showed histological atrophy, changes consistent with the anti-androgenic activity of the compound. 3. Liver weights were increased (P0.001) by +90% of control mean weights; hepatocyte hypertrophy and increased fat and glycogen were seen by light microscopy, and hyperplasia of smooth endoplasmic reticulin by transmission electron microscopy. 4. Assessment of liver mixed function oxidase activity demonstrated induction of cytochrome P450 enzymes, and increased isozyme 2B1/2 in males and 3A1 in both sexes was confirmed by immunohistochemical staining of liver sections. 5. An increase in bromodeoxyuridine (BrdU) labelling index of the liver was seen in females only. 6. This study is the first in a programme of work with CPA designed to investigate the effects of the compound in mice. It demonstrates that the hepatic effects of the compound which have been described in the rat also occur in mice.

Metastatic colorectal cancer is generally incurable. The most active regimen available, 5-fluorouracil (5-FU) and folinic acid (Leucovorin), produces response rates of approximately 25% to 30%. Methyl-lomustine is a nitrosourea with modest activity against colorectal cancer. A randomized trial was undertaken to evaluate the impact the addition of methyl-lomustine would have on response, duration of survival, and survival rates in patients with advanced colorectal cancer.The methyl-lomustine/5-FU/Leucovorin (MFL) regimen consisted of methyl-lomustine (110 mg/m2), administered on Day 1 of each 8-week cycle with six weekly boluses of 5-FU (600 mg/m2), and Leucovorin (500 mg/m2). The FL treatment arm consisted of the administration of 5-FU and Leucovorin as described above. Patients were evaluated for response and toxicity after each 8-week cycle.Of 319 patients included in this trial, 297 (93.1%) had disease evaluable for response and toxicity: 145 received MFL, and 152 received FL. In this trial, 526 courses of MFL and 529 courses of FL were administered. Methyl-lomustine/5-FU/Leucovorin treatment resulted in 4 complete and 30 partial responses (response rate, 21.9%), and FL treatment resulted in 9 complete and 33 partial responses (response rate, 26.4%). There was no significant difference in median survival duration between patients in the two arms (MFL = 48 weeks, FL = 51 weeks). However, MFL was significantly more toxic with greater myelosuppression than was FL (Grade 3-4 neutropenia: MFL = 56 patients, FL = 27 patients, P0.001; Grade 3-4 thrombocytopenia: MFL = 49 patients, FL = 2 patients, P0.001; Grade 3-4 anemia: MFL = 15 patients, FL = 6 patients, P0.001; and more prolonged median duration of granulocytopenia: MFL = 9 days, FL = 7 days, P0.001; and thrombocytopenia: MFL = 14 days, FL = 7.5 days, P0.001).Because the addition of methyl-lomustine in the MFL schedule markedly increased the toxicity of the regimen and because the FL regimen was as effective as MFL, the authors recommend that Leucovorin and 5-FU remain the treatment choice for treating patients with metastatic colorectal cancer.

Fernmetastasen solider Tumoren sind — auch bei unilokularer Manifestation — als Hinweis auf eine systemische Tumorerkrankung anzusehen und konnen mittels Operation oder Radiotherapie nur selten kurativ behandelt werden. In einzelnen Fallen, in denen die Metastasierung in nur einem Organ bzw. einer umschriebenen anatomischen Region auftritt, ist eine regionale Therapie zur erwagen. Das Konzept einer regionalen Tumorbehandlung wurde in den fruhen 50iger Jahren von Kopp et al. [1 J und Bierman et al. [2] entwickelt, die Stickstoff-Lost intraarteriell in verschiedene Tumoren infundierten. Die arterielle Leberperfusion mittels Zytostatika wurde von Watkins und Sullivan [3, 4] entwickelt, die uber einen Teflon-Katheter 5-Fluorouracil (5-FU) oder 2’-Deoxy-5-Fluorouridin (FUDR) mit Hilfe einer externen Infusionspumpe in die Arteria hepatica communis applizierten. Obwohl diese ersten Therapieversuche in zahlreichen Komplikationen resultierten, stellt die arterielle Leberinfusion (hepatic arterial infusion; HAI) aufgrund technischer Weiterentwicklungen heute fur zahlreiche Patienten eine erwagenswerte Therapieoption dar. Die regionale Therapie hepatischer Metastasen mit Standard-Chemotherapeutika ist aus mehreren Grunden durchfuhrbar: einer zweifachen Blutversorgung der Leber; einer hohen Gewebetoleranz gegenuber den meisten chemotherapeutischen Substanzen; geeigneter Pharmakokinetik der am haufigsten fur die HAI-Therapie angewendeten Zytostatika.

Mitoxantrone is an anthraquinone derivative that has demonstrated encouraging preclinical and clinical activity against a variety of human carcinoma cell lines and malignancies. Three Phase II studies of systemically administered mitoxantrone in patients with colorectal carcinoma failed to demonstrate any therapeutic activity, as did four Phase II studies of intravenous mitoxantrone in hepatocellular carcinoma. Two additional trials demonstrated limited activity when administered intravenously to patients with hepatocellular carcinoma. However, because this drug exhibits a steep dose-response curve, a Phase I-II trial of mitoxantrone by hepatic arterial infusion was initiated.Patients with hepatocellular carcinoma and metastatic colorectal carcinoma with liver only or liver-predominant disease were eligible for therapy. All patients underwent the placement of a percutaneous hepatic arterial catheter before each course of therapy, and the first cohort of patients was treated at 10 mg/m2/course on day 1 on a 28-day cycle. Dosages were escalated in increments of 2 mg/m2/course based on side effects and tolerance.Twenty-eight patients with bidimensionally measurable unresectable, liver-predominant disease were entered into this trial. The therapy was well tolerated, with only 5 courses of 55 being complicated by neutropenia and none associated with fever. Only one patient required a dosage reduction on the basis of toxicity (neutropenia). No complete or partial responses were observed.These data are consistent with a lack of therapeutic activity of mitoxantrone when administered by hepatic arterial infusion for the treatment of hepatocellular carcinoma or metastatic colorectal cancer.

The possible usefulness of low-lactose milk for those lactose-intolerant subjects who develop symptoms from milk consumption was investigated. In the first part of the study, 16 intolerant subjects (blood glucose rise less than 25 mg/100 ml) received low-lactose skim milk containing 15 g lactose (2.5 cups) and 7.5 g lactose (2.5 cups), regular skim milk containing 30 g lactose (2.5 cups), and all three milks plus a small breakfast. The low lactose milks produced significantly fewer symptoms. The food given with the milk had no significant effect on symptomatic response. The second group of 17 subjects received 25 g lactose in water (250 ml), skim milk (500 ml) and whole milk (500 ml); 10 g lactose in lactose-reduced skim (500 ml) and whole milk (500 ml) and whole milk (500 ml); and a placebo (250 ml). There was a significant positive relationship between amount of lactose consumed and symptom response. The form in which the lactose was administered (e.g., whole versus skim milk) was not significantly related to symptoms. It is concluded that in a symptomatic subjects a significantly greater quantity of low-lactose milk than regular milks can be consumed.

The effect of meropenem on animal kidneys has been assessed in rats (5 of each sex/group), rabbits (3 of each sex/group) and monkeys (3 of each sex/group) in comparative iv studies with ceftazidime, cefotaxime, cephaloridine and imipenem (without cilastatin). Diarrhoea occurred in rabbits and monkeys dosed with imipenem or meropenem. Emesis occurred only after the administration of imipenem to monkeys. After 14 days administration to rats evidence of nephrotoxicity was seen only in males dosed with cephaloridine (850 mg/kg); no changes were seen with ceftazidime, cefotaxime or meropenem (all at 1000 mg/kg). Four days after a single dose to rabbits renal tubular necrosis was seen in all animals receiving imipenem (150 mg/kg) and cephaloridine (250 mg/kg). Minimal histopathological changes to the kidneys were seen with cefotaxime, ceftazidime and meropenem (all at 400 mg/kg). After seven days' administration to cynomolgus monkeys imipenem (180 mg/kg) caused moderate to severe tubular necrosis. No tubular damage was seen with meropenem at 180 mg/kg or with cefotaxime or ceftazidime (both at 500 mg/kg). At 500 mg/kg meropenem caused mild tubular regeneration and/or fat accumulation in 3/6 animals, with mild tubular necrosis in one of these. The data from these three species indicate that meropenem has a low nephrotoxic potential in these animal models.

A redescription ofDiplograptus penna Hopkinson 1869 is given, based largely upon three-dimensional material. The significance of the discoveries is discussed with respect to the concept ofCystograptus Hundt 1942. The so-called «vesicles» of«Orthograptus» vesiculosus Nicholson andDiplograptus penna Hopkinson are interpreted as three-vaned structures.

It is heartening to note that relatively well nourished black children in the United States, a number of whom are, in all probability, lactose intolerant and most of whom are destined to become lactose intolerant adults, are able to consume nutritionally valuable quantities of milk with meals and, on the whole, do not report suffering from any abdominal pain or discomfort. It is also encouraging that this population of over two hundred primary school children consumed, on the average, 75 per cent of the 1/2 pt. milk served with lunch, reported drinking an average of three glasses of milk daily, and the vast majority reported liking milk and a number of other dairy products which are important nutrient sources in their diets.