Annals of oncology : official journal of the European Society for Medical Oncology
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The primary goal of phase I studies is to efficiently and accurately determine the recommended dose of a new agent for further investigation. Issues of concern ranging from the ethics of these trials to selection of starting dose and rapidity of dose escalation, have led to suggested modifications of the traditional phase I design. We wanted to assess the frequency with which these new approaches are being applied to recent phase I trials and, if possible, their impact. ⋯ Despite proposed new methodologies (particularly dose escalation) for phase I trials, very few are being employed in practice. A concerted effort should be made to prospectively evaluate these to determine which provides the best combination of safety and efficacy. In addition, the lack of standardization in the definition of limiting toxicity is surprising. Those involved in drug development should strive for agreement on the acceptable degree of toxicity for phase II dose selection.
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Methadone is a very useful drug in cancer pain because of its low cost, lack of active metabolites, high oral availability, and the rapid onset of its analgesic effect. It seems to be well tolerated in patients with difficult pain syndromes who are receiving high doses of opioids, and it may deter the development of tolerance, but a high individual variation in terminal elimination half-life can result in different rates and extents of drug accumulation. For this reason, oral patient-controlled analgesia with methadone was used in 24 advanced-disease patients with pain. ⋯ Patient-administered analgesia with oral methadone appears to be a simple, cheap and relatively safe technique for controlling cancer pain, permitting individualization by the patient him- or herself and avoiding the risk of accumulation. Continuous assessment is necessary.