European journal of cancer : official journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
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Treatment of cancer in childhood is an expensive undertaking for the health-care system and for the affected families. As there is a substantial burden of treatment-related morbidity, it is important to determine whether the effects of treatment are worth these monetary costs, especially from a societal perspective. Economic evaluation affords a comparison of the costs and consequences (effects) of relevant therapeutic alternatives. ⋯ Economic evaluation provides estimates of incremental discounted costs per discounted QALY gained. By almost any interpretative standard this appears attractive with respect to cancer in childhood. Examples are provided with the encouragement that economic evaluation be undertaken in more clinical trials in paediatric oncology.
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Randomized Controlled Trial Comparative Study Clinical Trial
Prevention of oral mucositis in paediatric patients treated with chemotherapy; a randomised crossover trial comparing two protocols of oral care.
This study compared the efficacy of two protocols for oral care using either chlorhexidine or benzydamine as oral rinses to alleviate mucositis in children undergoing chemotherapy. Eligible participants were randomised to receive either protocol for 3 weeks in a two-period crossover design. ⋯ According to this sequential analysis, the study could be terminated at the 34th within subject comparison, with a statistically significant reduction in ulcerative lesions (P<0.05) and severity of mucositis (P<0.05) in children on the chlorhexidine protocol. These findings suggest that chlorhexidine together with oral care might be helpful in alleviating mucositis when given prophylactically to children on chemotherapy, but the therapeutic benefit needs to be confirmed in a larger trial.
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The identification of genetic factors associated with either responsiveness or resistance to 5-fluorouracil (5-FU) chemotherapy, as well as genetic factors predisposing patients to the development of severe 5-FU-associated toxicity, is increasingly being recognised as an important field of study. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). Although the role of tumoral levels as a prognostic factor for clinical responsiviness has not been firmly established, there is ample evidence that a deficiency of DPD is associated with severe toxicity after the administration of 5-FU. ⋯ To date, 39 different mutations and polymorphisms have been identified in DPYD. The IVS14+1G>A mutation proved to be the most common one and was detected in 24-28% of all patients suffering from severe 5-FU toxicity. Thus, a deficiency of DPD appears to be an important pharmacogenetic syndrome.
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Pre-clinical toxicology studies in rodents and Phase I clinical trial data are summarised for 14 novel anticancer therapies. With only one exception, an antifolate antimetabolite, rodent toxicology predicted a safe Phase I trial starting dose and the majority of the dose limiting toxicities, in particular haematological toxicity. For targeted agents with well-defined pharmacodynamic markers, illustrated in the current study by 3 anti-endocrine drugs and one resistance modifier, the definition of a maximum tolerated dose can be avoided. Together with earlier data, the current study confirms that pre-clinical toxicology studies in a non-rodent species are not routinely needed for the safe conduct of early clinical trials with new cancer chemotherapies.
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Human tumour xenografts implanted subcutaneously (s.c.) into immunosuppressed mice have played a significant role in preclinical anticancer drug development for the past 25 years. Their use as a predictive indicator of probable clinical activity has been validated for cytotoxics. A retrospective analysis for 39 compounds where both extensive xenograft testing and Phase II clinical data were available, performed by the National Cancer Institute (NCI), has shown that 15/33 agents (45%) with activity in more than one-third of xenografts showed clinical activity (P=0.04). ⋯ Dependent upon the drug target, a slowing of xenograft tumour growth (cytostatic effect) rather than tumour shrinkage might be the major observed effect. Human tumour xenografts are also particularly useful in determining pharmacodynamic markers of response for subsequent clinical application. Nevertheless, it needs to be kept in mind that the use of xenografts is relatively time-consuming and expensive, raises animal ethical issues and there are instances where the model is inappropriate as a likely predictor of clinical outcome (e.g. inhibitors of the metastatic process and anti-angiogenic strategies as the vasculature is of murine origin).