Phase I and pharmacological studies of the cryptophycin analogue LY355703 administered on a single intermittent or weekly schedule.

LY355703 is a synthetic derivative of the marine cryptophycins, cytotoxic agents which induce mitotic arrest by binding at the microtubule vinca binding domain. Promising preclinical features of LY355703 were the 40-400 greater potency than paclitaxel or vinca alkaloids, the broad spectrum of antitumor activity in xenografts and the antitumour activity in multidrug resistant (MDR)-expressing murine tumours. Aims of this study were to define the maximum tolerated dose (MTD) and the dose recommended for Phase II, the pattern of toxicity, the pharmacokinetic profile and to document hints of antitumour activity of LY355703 given as 2-h infusion on day 1 every 3 weeks (Study 1) or, later on, on days 1, 8 and 15 every 4 weeks (Study 2).

A population-based study on the first forty-eight breast cancer patients receiving trastuzumab (Herceptin) on a named patient basis in Sweden.

Several studies have presented data on the efficacy and tolerability of trastuzumab within clinical trials. As a minority of patients is included in these trials, we undertook this retrospective study to describe trastuzumab therapy in clinical routine and its tolerability. We reviewed the medical records of the first 48 patients in Sweden who received treatment with trastuzumab on a named patient basis with (n = 29) and without (n = 19) chemotherapy.

Phase I and pharmacokinetic study of BIBX 1382 BS, an epidermal growth factor receptor (EGFR) inhibitor, given in a continuous daily oral administration.

The pyrimido-pyrimidine BIBX 1382 BS inhibits the intracellular tyrosine kinase domain of the epidermal growth factor receptor (EGFR), thus specifically reverting the aberrant enzymatic activity from overexpressed and constitutively activated EGFR. A phase I and pharmacokinetic study of this new specific molecule was carried out. After initially performing an accelerated titration design from the first toxicities onwards, a modified Fibonacci scheme was used to escalate the daily oral dose.

Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer.

The aim of this study was to determine the patient's preference for oral UFT/leucovorin (LV) or intravenous (i.v.) 5-fluorouracil (5-FU)/LV chemotherapy in metastatic colorectal cancer and to compare 5-FU exposure with these two treatment options.

Activity of the dolastatin analogue, LU103793, in malignant melanoma.

LU103793, a synthetic analogue of dolastatin 15, showed interesting pre-clinical activity in melanoma xenografts. In this phase II multicentre trial, 80 chemotherapy-naïve patients with metastatic melanoma received a total of 218 cycles of treatment. The response rate showed one complete and three partial responses of median duration six months (range 3-9.

Phase I and pharmacological study of weekly administration of the polyamine synthesis inhibitor SAM 486A (CGP 48 664) in patients with solid tumors. European Organization for Research and Treatment of Cancer Early Clinical Studies Group.

A single-agent dose-escalating Phase I and pharmacological study of the polyamine synthesis inhibitor SAM 486A was performed. A dosing regimen of four weekly infusions followed by 2 weeks off therapy was studied. Fifty patients were entered into the study.

[Bacterial colonization of the stomach caused by acid neutralization and inhibition of stomach emptying].

Gastric bacterial overgrowth was studied in 8 healthy volunteers. Total bacterial counts, nitrate-reducing bacteria and nitrite concentration were determined in fasting gastric juice before and after 4 weeks of treatment with a strong or with a mild antacid drug, a placebo preparation and the spasmolytic agent papaverine which is known to inhibit gastric evacuation. Placebo therapy and the mild antacid did not change any of the above parameters studied.

[Dynamics of endogenous bacterial nitrite formation in the stomach. 1. Follow-up studies in humans under natural conditions].

The fasting gastric secretion was analysed both bacteriologically and chemically in 15 young, voluntary test subjects with histories of a healthy stomach and physiological gastric secretion tests (Basal Acid Output, Peak Acid Output) made at regular intervals of two and 4 weeks over a period of three and six months. Two thirds of the persons studied showed during the entire period of examination the same pH values with tolerable variations and, as a result, the same order of magnitude for the total germ count, the colony count of the nitrite-forming bacteria and for the NO2- concentration. From this the conclusion can be drawn that, depending on the acidity of the individual stomach, there is an autonomous bacterial flora, which repeated examinations have shown to remain unaltered in quality and quantity.

[Endogenous synthesis of carcinogenic N-nitroso compounds: bacterial flora and nitrite formation in the healthy human stomach].

The endogenous synthesis of cancerogenic N-nitroso compounds: Bacterial flora and nitrite formation in the human stomach. In the discussion of the endogenous nitrosamine synthesis, nitrites play a decisive role. Since in a healthy stomach the acidity important for the nitrosamine formation is present, but since this acid environment is hostile to the bacterial growth and thus counteracts bacterial endogenous nitrite formation, the oral cavity has so far been regarded as the main site of endogenous nitrite formation.