ABSTRACT
BACKGROUND: The Common Toxicity Criteria adopted by the NCI in the USA for grading toxicity in cancer clinical trials have been compared to the WHO scoring system which is still in use in Europe. PATIENTS & METHODS: Sixty-six patients undergoing emetic chemotherapy at the Netherlands Cancer Institute completed questionnaires, 32 according to the WHO criteria and 34 to the Common Toxicity Criteria, on the severity, frequency and duration of gastro-intestinal toxicity. Their answers were then compared to the scores coded by research nurses and physicians. The nurses coded acute toxicity when the patients were discharged, and the doctors coded overall toxicity when the patients returned for the subsequent course of chemotherapy. To evaluate the coding systems, an estimate was made of the percentage agreement between the patients' answers and the nurses' and doctors' ratings. RESULTS: The percentage agreement of the Common Toxicity Criteria with the patients' own experiences of nausea and vomiting was considerably better than that of the WHO score. The Gamma statistic confirmed this. The Common Toxicity Criteria have now been adopted for grading toxicity in studies of the Early Clinical Trials Group of the EORTC and are recommended for use in other clinical trials.
Subject(s)
Antineoplastic Agents/adverse effects , Nausea/chemically induced , Vomiting/chemically induced , Adult , Aged , Clinical Trials as Topic , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , World Health OrganizationABSTRACT
Vintriptol, a tryptophan ester of vinblastine, is a new vinca alkaloid derivative. Preclinical studies have demonstrated its antitumour activity in a large variety of animal models. In this phase I study, 47 patients with advanced cancer were exposed to escalating doses of vintriptol, starting at 6 mg/m2 and following a modified Fibonacci schedule. The drug was administered as an intravenous push on a weekly schedule. Myelosuppression was the dose-limiting toxicity and the maximum tolerated dose was 45 mg/m2. Other toxicities consisted of mild nausea and vomiting and the occurrence of fever and dryness of the mouth immediately after drug administration. Neurotoxicity, a major side-effect of other vinca alkaloids, was insignificant. 1 partial remission in a patient suffering from colorectal cancer and 1 minor response in a patient with a metastatic tumour of the cutaneous appendagous glands were documented. Pharmacokinetics of vintriptol were evaluated at the highest dose levels. A dose schedule of 40 mg/m2 vintriptol per week is recommended for phase II studies.
Subject(s)
Antineoplastic Agents/therapeutic use , Vinblastine/analogs & derivatives , Adult , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Drug Evaluation , Female , Fever/chemically induced , Humans , Leukopenia/chemically induced , Male , Middle Aged , Neoplasms/blood , Neoplasms/drug therapy , Thrombocytopenia/chemically induced , Vinblastine/therapeutic useSubject(s)
Clinical Trials as Topic , Neoplasms/therapy , Oncology Nursing , Academies and Institutes , Humans , Netherlands , ResearchABSTRACT
Tamoxifen and N-desmethyltamoxifen plasma concentrations were found to be similar after a first single dose and during two months therapy with Tamoplex or Nolvadex in groups of 6 and 8 patients, respectively. Single dose absorption results in 10 healthy male volunteers demonstrated bioequivalence of Tamoplex and Nolvadex 10 mg tablets. A large interindividual variation in tamoxifen absorption data was observed, probably related to the dominating metabolic clearance of tamoxifen.
