European journal of cancer & clinical oncology最新文献

Nausea and vomiting occur in all patients following high-dose cisplatin chemotherapy, unless an effective anti-emetic is administered. Early clinical studies therefore examined ondansetron treatment to establish an optimal dosing schedule for acute emesis. Pilot studies suggested that a daily dose of 32 mg ondansetron, given as a continuous intravenous infusion or intermittently on a mg/kg basis, gives optimum control of emesis, and was therefore selected for comparative studies. Efficacy was confirmed in two randomised, double-blind, crossover studies comparing ondansetron and metoclopramide. Ondansetron was superior to high-dose metoclopramide in controlling acute emesis and nausea, and there was a significant patient preference for ondansetron. These effects may be related to ondansetron's greater potency as a competitive 5-HT3 antagonist. In addition, ondansetron did not induce any extrapyramidal reactions, confirming the absence of any dopamine antagonist activity.

Amphotericin B remains the treatment of choice for systemic fungal infections, but amphotericin B is toxic and is often not effective in treating disseminated infections. Liposome intercalation of amphotericin B reduces the toxicity associated with amphotericin B and targets reticuloendothelial tissues most heavily involved in fungal infections. The targeted delivery and reduced toxicity of liposomal amphotericin B improves the therapeutic index of amphotericin B. Although liposomes have been shown to effectively treat a variety of experimental and human fungal infections, the optimal composition of liposomal amphotericin has not been established. Vesicle type, lipid content, size, and conditions of storage markedly affect toxicity, therapeutic efficacy, and tissue distribution. In vitro studies have been poor predictors of in vivo efficacy and toxicity. Animal models can be used to evaluate in vivo the optimal liposome preparation. Liposomal amphotericin B appears to be an improved means of amphotericin B delivery and may improve the treatment of patients with systemic fungal infections.

Ondansetron tablets contain ondansetron base as the hydrochloride dihydrate, lactose, microcrystalline cellulose, starch and magnesium stearate. Tablets sampled at the beginning and end of the compression process have good content uniformity and drug content, showing that there is no segregation or loss of the drug substance during tabletting. The release of drug substance is related to the tablet disintegration time. Tablets with disintegration times of 3 and 10 min release 85% of the drug substance in approximately 6 and 20 min respectively. Satisfactory bioavailability has been demonstrated. The tablets have good stability, and have a shelf life of 2 years when stored below 30 degrees C.

Although significant advances have been made in the treatment of malignant diseases, many agents cause nausea and vomiting severe enough to cause patients to be hospitalised or to refuse further treatment. Several classes of anti-emetics are currently used, but are only partially effective and are often associated with side effects such as extrapyramidal reactions. Ondansetron, a specific 5-HT3 antagonist, has been fully evaluated in the clinic, both as an intravenous and oral presentation, and in open studies in patients receiving non-cisplatin chemotherapy regimens it was highly effective in controlling acute and delayed emesis -- more than 90% of patients had a complete or major response to treatment. In three randomised, double-blind studies comparing ondansetron and metoclopramide, ondansetron was found to be superior in the control of both emesis and nausea. Ondansetron was also shown to be safe and well tolerated; in particular, no extrapyramidal reactions were reported.

Recent studies indicate that different types of antitumour lymphocytes (T and non-T) can be generated in vitro and in vivo after exposure to recombinant interleukin-2 (rIL-2). In vitro it is possible to selectively expand the CD3 cells by using anti-CD3 monoclonal antibody and rIL-2. Adherence can select a minor subpopulation of lymphokine-activated killer (LAK) cells (A-LAK) endowed with a higher lytic activity. We have investigated whether melanoma-specific T-lymphocytes can be obtained to be used for therapy or endogenously expanded in vivo by the appropriate use of limited amounts of rIL-2. Clonal analysis of lymphocytes obtained either from tumour lesions or from blood indicated the existence of melanoma-restricted T-lymphocytes, both with cytotoxic or helper function. Though a minority, these cells can be generated and expanded with low amounts of rIL-2 (3-30 Cetus U/ml) in the presence of autologous melanoma and B-cells. The use of rIL-1 and rIL-4, together with rIL-2 at certain phases of T-lymphocyte growth, can help in expanding more selectively the melanoma-specific cells. These T-cells are major histocompatibility complex-restricted in their killing but they also need to see adhesion molecules (ICAM-1) on the target cells. New clinical protocols can thus be conceived on the basis of some of these results.

Evaluating response in cancer is a well established practice, depending on the recognition of complete response, partial response, stable disease and progressive disease. For chemotherapeutic drugs, only those patients achieving a complete response experience an increase in survival. Partial response merely indicates that the drug has some activity in that disease. What the patient wants is not active drugs but prolonged survival with good quality of life. It is well recognised that tumours may remain dormant for many years, and that even those patients with complete responses to chemotherapy usually have minimal residual disease. It is assumed that such minimal disease is controlled and held in check by a biological process. The principal aim of biological response modifiers is to enhance this effect so as to control an even larger tumour load. It therefore follows that removal of all tumour is not the only benefit, and that stable disease and even slower progression might translate to longer survival. Survival curves are the acid test and we should expect longer survival even for those patients failing to achieve complete response if we are to establish that life imprisonment is as effective in cancer treatment as capital punishment.