No abstract

The biochemical background of the intestinal side effects of cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (CBDCA) and cis-diisopropylamine-trans-dihydroxy-dichloro platinum (IV) (CHIP) was compared with those of cis-diamminedichloroplatinum (II) (CDDP). Biochemical investigations were carried out on mucosal cells isolated by a combined chemical-mechanical method from the total length of the small intestine. After treatment with single, equitoxic doses of Pt analogues, the activities of thymidine kinase (TK) EC 2.7.1.21, sucrase (SUC) EC 3.2.1.26, maltase (MAL) EC 3.2.1.20, and protein content showed dose-dependent decreases, whereas the activity of alkaline phosphatase (AP) EC 3.2.1.20 increased slightly. The nadir of enzyme activity changes occurred 24-48 h after treatment. For the regeneration of the mucosa more than 96 h was necessary. Of the platinum analogues studied, CHIP proved to be the most toxic to the small intestine. While the highest doses of CDDP and CBDCA (0.66 x LD50) caused significant but less than 50% decreases in TK, SUC, MAL, and protein content (PROT), the CHIP doses needed for 50% reduction were between 0.44-0.66 x LD50.

Fifty immunocompromised children with varicella who exhibited no signs of dissemination were treated with intravenous acyclovir or placebo in a double-blind, randomized study. Twelve of 25 placebo recipients were withdrawn from treatment because of their deteriorating condition and were given open acyclovir therapy; only one of 25 recipients of acyclovir was similarly withdrawn (P less than .001). Among those patients who did not receive open treatment, acyclovir significantly reduced time to full crusting (P = .01). Overall, acyclovir, as judged by the physician, significantly improved the patients' condition.

No abstract

We have performed a high-dose clinical and pharmacokinetic trial with vinorelbine administered as a bolus injection every 21 days. The aim was to evaluate a schedule with longer treatment intervals than one week and to determine the toxicity pattern of such a schedule. A total of 13 patients (pts) with solid tumors (non-small-cell lung [3 pts], unknown primary [3 pts], mesothelioma [2 pts], colon/rectum, sarcoma, thyroid, head/neck and cervix [1 pt each]) were entered [9 male, 4 female, median age: 56 years (range: 37-69)]. Dose levels were 35, 40 and 45 mg/m2 with a total of 26 cycles administered. At 40 mg/m2, 2/6 pts developed grade 4 granulocytopenia. 1/1 pt at 45 mg/m2 developed a grade 4 leuko- and granulocytopenia. Non-hematological toxicities were mild to moderate. Neurologic toxicity except for constipation was mild. Constipation occurred at 35 mg/m2 in 1/6 pts WHO grade 4, at 40 mg/m2 in 2/6 pts WHO grade 3 and at 45 mg/m2 in 1/1 pt WHO grade 4 and was due to neurotoxicity. No objective antitumor response was observed. Vinorelbine pharmacokinetics were analysed in whole blood and plasma and were similar to previously published studies using < or = 30 mg/m2. Our results confirm a high affinity of vinorelbine to corpuscular blood elements. We conclude that the MTD of vinorelbine administered once every 21 days as bolus injection is 40 mg/m2, the dose-limiting toxicities are constipation and granulocytopenia and the recommended dose for subsequent Phase II trials is 35 mg/m2.