We assessed the impact of prophylaxis with the oral itraconazole solution and amphotericin B solution on fungal colonization and infection in a randomized study among patients with hematological malignancies and neutropenia. Infecting and colonizing Candida strains of patients suffering from candidiasis were genotyped by random amplification of polymorphic DNA (RAPD) analysis. A total of 106 patients were evaluated in this study: 52 patients in the itraconazole and 54 in the amphotericin B arm. During neutropenia fungal colonization in the oropharynx occurred in 11 (19.6%) and 24 (40.6%) and in the rectum in 11 (19.6%) and 23 (38.9%) courses in the itraconazole and amphotericin B groups ( P<0.05), respectively. Candida albicans was the most prevalent species in both study groups. Mixed fungal colonization with Candida krusei and Candida glabrata was increased in the amphotericin B group, yet without clinical importance since infections were due to C. albicans. The occurrence of invasive candidiasis was significantly increased in multicolonized compared to monocolonized patients. In the amphotericin B group 20 and in the itraconazole group 2 neutropenic patients showed multicolonization with Candida spp. ( P<0.05). Overall fungal infections were 3.8% in the itraconazole and 14.8% in the amphotericin B group ( P<0.05). RAPD typing showed oropharynx strains involved in superficial infections in four of five patients. In all four patients with deep fungal infections, it appears that the colonizing rectum strains were identical to infecting strains of Candida spp. Itraconazole solution significantly reduced Candida colonization and infection compared to amphotericin B solution. Most patients remained infected with the colonized strains for the entire study period, irrespective of antifungal prophylaxis.

We performed a randomized trial to compare the safety and efficacy of itraconazole with fluconazole in preventing fungal infections in patients undergoing allogeneic stem cell transplantation (SCT). Itraconazole (intravenous 200 mg daily, or oral solution 2.5 mg/kg 3 times daily) and fluconazole (intravenous or oral, 400 mg daily) were administered with the start of conditioning therapy, until at least 120 days after SCT. After enrollment of the first 197 patients, a data and safety monitoring board reviewed potential drug-related toxicities. Patients who received itraconazole developed higher serum bilirubin and creatinine values in the first 20 days after SCT, with highest values in patients who received itraconazole concurrent with cyclophosphamide (CY) conditioning. Analysis of CY metabolism in a subset of patients demonstrated higher exposure to toxic metabolites among recipients of itraconazole compared with fluconazole. These data suggest that azole antifungals, through differential inhibition of hepatic cytochrome P-450 isoenzymes, affect CY metabolism and conditioning-related toxicities.

Although all first-generation 5-HT(3) receptor antagonists demonstrate efficacy in preventing acute chemotherapy-induced nausea and vomiting (CINV), effective prevention of delayed CINV has not yet been achieved. This study compared the efficacy and tolerability of palonosetron, a novel, second-generation 5-HT(3) receptor antagonist, with ondansetron.

HER-2/neu oncogene expression is modulated by an estrogen-sensitive binding site in the HER-2/neu promoter. Utilizing the circulating antigen of HER-2/neu in serum (sHER-2/neu) as a surrogate marker we investigated whether ovarian ablation by adjuvant therapy leads to an upregulation of HER-2/neu in breast cancer patients.

Clinical observations suggest that prolonged treatment with megestrol can lead to Cushing-like symptoms, while withdrawal of prolonged treatment with megestrol may result in adrenal insufficiency. However, only little is known about the acute effects of megestrol on the hypothalamic-pituitary-adrenal (HPA) axis. As part of an endocrine study, we evaluated the acute effects of megestrol, hydrocortisone and placebo on morning cortisol and ACTH levels.

To determine the acceptability of short term neo-adjuvant maximal androgen deprivation (MAD) to patients treated with external beam radiation for locally advanced prostate cancer.

Many orange-coloured fruits contain beta-cryptoxanthin in its non-esterified as well as its esterified form. Information concerning the absorption of beta-cryptoxanthin, especially with regard to the metabolism of its fatty acid esters, is rather scarce. The present study assessed the plasma concentration reached after consumption of a single dose of native beta-cryptoxanthin esters from papaya (Carica papaya L.) or non-esterified beta-cryptoxanthin in equal total amounts. In a randomized, single-blind crossover study, twelve subjects were served a portion of yoghurt containing esterified or non-esterified beta-cryptoxanthin (1.3 mg absolute) together with a balanced breakfast. Between the two intervention days, there was a 2-week depletion period. After a fasting blood sample had been taken, futher samples were taken from the subjects at 3, 6, 9, 12 and 24 h. The concentration of non-esterified beta-cryptoxanthin in the whole plasma was determined by HPLC; beta-cryptoxanthin identification was confirmed by liquid chromatography-atmospheric pressure chemical ionization-MS analyses. Irrespective of the consumed diet, the plasma beta-cryptoxanthin concentrations increased significantly (P=0.05) and peaked after 6-12 h. The concentration curves, as well as the areas under the curves, were not distinguishable according to two-sided F and t tests (P=0.05). Standardization of beta-cryptoxanthin concentrations to plasma triacylglycerol and cholesterol had no impact on the results. Thus, the present study indicates comparable bioavailability of both non-esterified beta-cryptoxanthin and mixtures of beta-cryptoxanthin esters. The results support the existence of an effective enzymatic cleavage system accepting various beta-cryptoxanthin esters.

The authors present the Hungarian interim analysis and experience with the BCIRG 001 randomized, multicentric, phase III clinical trial comparing TAC (docetaxel, doxorubicin, cyclophosphamide) and FAC (5-fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant treatment of node positive breast cancer patients. The results are presented according to international data.

To investigate the population pharmacokinetics of daunorubicin in children after administration of liposomal daunorubicin (Daunoxome).

This dose-finding, placebo-controlled study evaluated the safety and efficacy of darbepoetin alfa administered every 3 weeks (Q3W) to anaemic patients receiving chemotherapy. In part A, patients (haemoglobin </=110 g/l) were randomised in a 1:4 ratio to receive 1 of 6 doses of darbepoetin alfa (4.5, 6.75, 9.0, 12.0, 13.5 and 15.0 microg/kg) or placebo Q3W for 12 weeks. In part B, patients received open-label darbepoetin alfa. Patients (n=249) were evaluated for safety, haemoglobin endpoints and red blood cell (RBC) transfusions. Darbepoetin alfa given at doses ranging from 4.5 to 15.0 microg/kg Q3W was well tolerated and comparable to placebo in terms of safety. No neutralising antibodies were detected. All doses (from 4.5 to 15 microg/kg) reduced transfusions compared with placebo, and resulted in >50% of patients achieving a haematopoietic response. Administration of darbepoetin alfa Q3W has a tolerable safety profile and effectively ameliorates anaemia due to chemotherapy.

This phase III study compared the efficacy of the new potent bisphosphonate, ibandronate, with placebo as intravenous (i.v.) therapy in metastatic bone disease due to breast cancer.

Women with hormone-responsive metastatic breast cancer (MBC) may respond to or have stable disease with a number of hormone therapies. We explored the efficacy and safety of the steroidal aromatase inactivator exemestane as first-line hormonal therapy in MBC in postmenopausal women.

This randomized, double-blind, phase II study assessed two doses of the selective estrogen receptor modulator arzoxifene in women with advanced breast cancer. The primary end point was to choose the best of two doses of arzoxifene based on the response rate or the clinical benefit rate (CBR). Pharmacokinetics and toxicities were also assessed.

The objective was to evaluate the efficacy and safety of a novel intratumoral cisplatin/epinephrine injectable gel (CDDP/epi gel) for local control and palliation of tumor-related symptoms in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

To determine single-and multiple-dose pharmacokinetics of liposomal-all- trans -retinoic acid (Atragen) following intravenous and oral ATRA (Vesanoid) administration in healthy volunteers.

The standard treatment for patients with clinically resectable rectal cancer is surgery. Postoperative radiochemotherapy (RCT) is recommended for advanced disease (pT3/4 or pN+). In recent years, encouraging results of pre-operative radiotherapy have been reported. This prospective randomized phase-III-trial (CAO/ARO/AIO-94) compares the efficacy of neoadjuvant RCT to standard postoperative RCT. We report on the design of the study and first results with regard to toxicity of RCT and postoperative morbidity.

To investigate the effects of Nasea on prevention of gastrointestinal side effects caused by chemotherapeutic drugs.