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Aims and Background: Doxifluridine is a new fluoropyrimidine that has excellent absorption by the gastrointestinal tract when given orally. The aim of the study was to determine the disposition of doxifluridine and fluorouracil when the former is given orally for 5 days and to assess whether their pharmacokinetics are influenced by demographic or biologic parameters., Methods and Study Design: Twenty colorectal cancer patients received levo-leucovorin, 25 mg orally on days 1-5, followed 2 hrs later by doxifluridine, 1200 mg/m2; the cycle was repeated every 10 days. Doxifluridine and fluorouracil levels were measured by reverse-phase high-performance liquid chromatography during the first cycle of therapy. The lowest dose given over the first 24 hrs was 1750 mg and the highest was 2500 mg., Results: The distribution of doxifluridine parameters remained the same between days 1 and 5, with an AUC that ranged between 72.2 and 74.5 mmol h/l and a C max that remained in a narrow band of 67.1 to 68.3 mmol/l. In contrast, the variability of fluorouracil parameters increased from day 1 to day 5, with an AUC of respectively 5.46 and 7.52 mmol h/l and a C max that increased from 5.81 on day 1 to 7.34 mmol/l on day 5. A significant correlation between the AUC of doxifluridine and fluorouracil was found on day 1 and on day 5 (P < 0.001). None of the demographic or biologic parameters considered was significantly related to pharmacokinetic parameters. Fluorouracil levels remained low in comparison with levels measured after classical fluorouracil therapy, although detectable for a longer time., Conclusions: A large interpatient pharmacokinetic variability was observed without any significant correlation with the clinical parameters studied.

Aims and Background: Ondansetron, a selective serotonin type 3 receptor antagonist, has been investigated at a wide range of doses. Recent studies have demonstrated that a single dose of this drug is active, either by intravenous bolus or continuous infusion. The main aim of this study was to evaluate the efficacy of a low dose of ondansetron in a simple and feasible schedule as follows: ondansetron 8 mg i.v. and dexamethasone 8 mg i.v. given before chemotherapy on day 1. Oral ondansetron 8 mg was subsequently given in the evening of day 1, and then even 12 hours on days 2, 3 and 4., Methods: Forty-chemotherapy-naive patients receiving cisplatin, dacarbazine or other emetogenic drugs were enrolled in the study. All courses of chemotherapy were given in an outpatient setting., Results: During the first cycle, complete control of acute emesis was achieved in 88% of cases, and no delayed emesis was recorded in 76%; acute and delayed nausea were absent in respectively 78% and 69% of cases. During the second, third and fourth cycles complete control of acute emesis was achieved in respectively 92%, 80% and 86% of cases, and no delayed emesis was recorded in 71%, 82% and 82%. No severe adverse effects were observed. CONCLUSIONS; Our study shows that a single intravenous administration of low-dose ondansetron combined with intravenous dexamethasone and followed by oral ondansetron twice daily is effective in controlling emesis in patients receiving chemotherapy, and that it is feasible as an ambulatory regimen.

Aims and Background: Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue that induces the suppression of gonadal steroidogenesis, and it could therefore be a medical alternative to irreversible surgical castration. We report the clinical and endocrine results from 40 goserelin-treated premenopausal patients with advanced breast cancer., Methods: A depot formulation of the drug (3.6 mg s.c.) was administered fortnightly for the first 4 doses, and monthly thereafter. Gonadotrophins and estradiol (E2) levels were measured before and at specific times during the treatment., Results: Objective responses were observed in 17 of the 38 evaluable patients (45%), six of whom achieved complete remission. The best responses were observed on soft tissues (65%). Castration E2 levels were achieved in all of the patients., Conclusions: Our results confirm that goserelin is as effective as surgical oophorectomy in premenopausal advanced breast cancer.

Aims and Background: Interferon (IFN) and interleukin-2 (IL-2) have been proven to be active agents in the treatment of malignant melanoma, but the most effective doses of these cytokines were often associated to important side effects and poor patient compliance. Recently, the subcutaneous administration of low-dose IL-2 was found to be a well-tolerated and effective treatment for renal cancer. Since the combination of low doses of IL-2 and IFN has been hypothesized to have synergistic biologic and cytotoxic effects, we evaluated feasibility and patient compliance of a scheme that combined recombinant IFN-alpha (rIFN-alpha) (3 million units by intramuscular injection, 3 times a week) plus low-dose IL-2 (9 million IU, 3 to 5 times a week) administered subcutaneously for 2 weeks every 28 days., Results: Fifteen patients with disseminated malignant melanoma previously treated with chemotherapy entered the study. All but the first 2 self-administered the therapy at home and were followed in an out-patient setting. None of them required in-patient care for toxicity. No WHO grade 4 side effects were detected; the only grade 3 side effects were fever and asthenia in 5% of the cycles. Mild hematologic toxicity (grade 2) was observed at the highest weekly dose of IL-2. No major responses were observed in this subset of heavily pretreated patients., Conclusions: We conclude that the regimen studied is feasible and well tolerated in an out-patient setting, but it is unlikely to be effective. The good patient compliance makes this schedule eligible to evaluate whether IL-2 plus rIFN-alpha can enhance the results of chemotherapy in this disease.