Annals of oncology : official journal of the European Society for Medical Oncology
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The problems related to requests for euthanasia by terminal patients; the variations in attitude of palliative care physicians and the possibility that availability of the best palliative care might obviate the problem by eliminating requests for euthanasia, are under discussion. ⋯ The attitudes of physicians practising palliative care in Italy are not different from those reported by previous studies which investigated the attitude of other health professionals. There was no agreement about whether the best palliative care might reduce requests for euthanasia by terminal patients.
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Randomized Controlled Trial Clinical Trial
Treatment of metastatic melanoma with combined chemotherapy containing cisplatin, vinblastine and dacarbazine (CVD) and biotherapy using interleukin-2 and interferon-alpha.
Metastatic melanoma is commonly treated with chemotherapy and/or biological agents used separately. In this study we have investigated the efficacy of combined chemotherapy using cisplatin, vinblastine, DTIC (CVD) and biological therapy using interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) in patients with metastatic melanoma. ⋯ The sequential combination of CVD with IL-2 + IFN-alpha appears to have produced an increase in the number of durable responses in patients with metastatic melanoma. The toxicity of this program, although severe, was manageable. The biochemotherapy regimen produced an apparent increase in the median survival compared to that observed with the CVD regimen. However, a prospective comparison of these two regimens will be required to confirm these observations.
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Clinical Trial
Rationale for the dosage and schedule of CPT-11 (irinotecan) selected for phase II studies, as determined by European phase I studies.
CPT-11 (irinotecan), a camptothecin-derived anticancer agent with DNA topoisomerase 1 inhibitory activity, has demonstrated a broad spectrum of in vitro and in vivo activity in solid tumour models including multidrug-resistant tumours. This review details the rationale for the dosage schedule of CPT-11 selected for phase II studies, based on the results of 3 European phase I dose-escalating trials in patients with solid tumours. ⋯ CPT-11 350 mg/m2 administered as an intravenous infusion once every 3 weeks was chosen for further evaluation in early phase II studies, since this dosage regimen allowed the highest dose intensity with the least toxicity and was convenient for outpatient use. The place of higher doses (with intensive antidiarrhoeal support) and other administration schedules (e.g., protracted infusion) warrant further investigation.
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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.