Annals of oncology : official journal of the European Society for Medical Oncology
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This state-of-the-art review describes the development, over the past 12 years, of new agents for the control of chemotherapy- and radiotherapy-induced emesis. While the mechanism of chemotherapy-induced nausea and vomiting is still not fully understood, significant progress in prevention of the symptoms has been achieved. The discovery that high-dose metoclopramide was very effective in antiemetic control ultimately led to the development of a new class of antiemetics, the 5-HT3 receptor antagonists, of which tropisetron is the most recent to be introduced. ⋯ The new 5-HT3 receptor antagonists do not demonstrate any of the distressing extrapyramidal reactions so frequently encountered with conventional antiemetics acting at dopamine receptor sites. Mild headache is the most characteristic side effect of this class of agents. The major advantages of the newer 5-HT3 receptor antagonists, such as tropisetron, over the conventional antiemetic regimens are convenience, flexibility and, above all, single-dose usage.
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Tropisetron is a 5-HT3 receptor antagonist which suppresses nausea and vomiting induced by cancer chemotherapeutic agents. In this study, tropisetron was evaluated on a compassionate-need basis in 545 cancer patients who had either proved refractory to antiemetic treatment during previous chemotherapy or who were at high risk of emesis as a result of current therapy. Tropisetron (5 mg or 10 mg) was administered as a 15-minute infusion prior to chemotherapy, with the further possibility of an additional dose, either orally or parenterally, on one or more subsequent days. ⋯ More than 80% of patients with a complete response in Course 1 had a complete response in Course 2 and of the partial responders in Course 1, 37% achieved a complete response in Course 2. Of the 7.6% failures in Course 1, a further 26% achieved a complete response in Course 2. Tropisetron was well tolerated, with adverse effects recorded in only 45 (8%) patients.
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Multicenter Study Clinical Trial
Tropisetron in the prevention of chemotherapy-induced nausea and vomiting: the Nordic experience.
An open, non-comparative, Nordic multicenter study was performed during 1991-1992 to evaluate the new 5-HT3 receptor antagonist tropisetron, as an antiemetic agent in various types of cancer chemotherapy. More than 600 patients were recruited from 16 cancer centers in Sweden, Finland and Denmark. In this report an interim analysis on 231 patients is presented. ⋯ Sex and age were significant prognostic factors with regard to antiemetic response. Adverse events were recorded in 19%-36% of the cases during long-term follow-up. Headache (16%) and constipation (5%) were most frequent.(ABSTRACT TRUNCATED AT 250 WORDS)
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Comparative Study
The fate of abstracts submitted to a cancer meeting: factors which influence presentation and subsequent publication.
Abstracts that are published in the proceedings of meetings receive minimal peer-review, but may be referenced or used to make decisions about management of patients. We have studied factors which influence the probability of acceptance for presentation, and of subsequent publication of articles, from abstracts included in the Proceedings of the American Society of Clinical Oncology (ASCO). From a random sample of 197 abstracts submitted to the 1984 meeting, 81 were accepted for presentation and a Cancerline computer search revealed 103 papers that were published subsequently in peer-reviewed journals. ⋯ There were no significant differences in the frequency of citation of abstracts that did or did not lead to subsequent publications. We made detailed comparisons of abstracts and subsequent papers for 18 randomized phase III trials. For 15 studies (83%), there was good correlation between the conclusions of the article and of the abstract.(ABSTRACT TRUNCATED AT 250 WORDS)
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Two murine tumour models, the L1210 leukaemia and the ADJ/PC6 plasmacytoma, have featured prominently in the preclinical development of platinum drugs. Mindful of the unequivocal need to discover new platinum-based drugs exhibiting activity in cisplatin/carboplatin refractory and relapsed cancers, and to devise clinically-predictive screening models, we have generated resistance in vivo in the ADJ/PC6 plasmacytoma to cisplatin (19- to 21-fold), to carboplatin (25-fold), iproplatin (greater than 14-fold) and tetraplatin (10-fold). The chemo-sensitivity profiles of these tumours have been compared with L1210 leukaemia lines resistant to either cisplatin (10-fold) or tetraplatin (34-fold). ⋯ In particular, the L1210/cisplatin resistant model exhibited cross-resistance to carboplatin and iproplatin, whereas the diaminocyclohexane (DACH)-containing complex, tetraplatin, was even more active in the cisplatin resistant tumour than in the 'wild-type' tumour. The ADJ/PC6/cisplatin resistant tumour, however, was cross-resistant, not only to carboplatin and iproplatin, but also to tetraplatin. These data provide an important caveat on the adoption of single acquired resistant animal tumour models for platinum drug development.