The purpose of this study was to evaluate whether radiotherapy with carboplatin would result in longer survival than radiotherapy alone in elderly patients with unresectable stage III non-small cell lung cancer (NSCLC).

Although intravenous (IV) 5-fluorouracil (5-FU) and uracil/futraful (UFT) have comparable antitumour efficacy in the treatment of metastatic colorectal cancer (MCC), we wanted to assess which of these two regimens would be preferred by our patients. We randomized 20 previously untreated patients with MCC at our centre to receive oral UFT or bolus IV 5-FU both associated with leucovorin. After the first cycle patients were crossed over to the other arm. Before the third cycle we left patients to choose one of the regimens to continue their treatment until disease progression. Two patients chose 5-FU and 18 chose UFT (P < 0.001). Fewer side effects (50%) and convenience of home treatment (40%) were the main reasons for their choice for the oral regimen. UFT induced less mucositis (P = 0. 02) and diarrhoea (P = 0. 01). We conclude that convenience and lower toxicity may explain the observed preference for oral UFT.

To evaluate plasma cystatin level as a covariate to predict topotecan pharmacokinetics. Cystatin C, a member of the cystatin superfamily of cysteine proteinase inhibitors, has been recently proposed as an alternative endogenous marker of glomerular filtration. Renal function is known as a key factor of topotecan clearance.

The primary objectives of this study were to characterize the absolute bioavailability of azacitidine after subcutaneous (SC) administration and to compare the single-dose pharmacokinetics of azacitidine following SC and intravenous (IV) administration. Six patients with myelodysplastic syndromes were randomly assigned according to a crossover design to treatment A, consisting of azacitidine administered as a single 75-mg/m(2) SC dose, or treatment B, consisting of azacitidine administered as a single 75-mg/m(2) IV infusion dose over 10 minutes. A minimum of 7 days and a maximum of 28 days were permitted between treatments. The study demonstrated good bioavailability of a SC azacitidine dose compared to an IV infusion treatment. The exposure profiles following SC drug administration illustrate measurable azacitidine levels with bioavailability (AUC) values within 89% of those measured following IV administration (range, 70%-112%). The median IV half-life was 0.36 +/- 0.02 hours compared to 0.69 +/- 0.14 hours for SC administration. Regardless of the route of administration, a single dose of azacitidine, 75 mg/m(2), was generally well tolerated.

Gender-related aspects in chronic myeloid leukemia (CML) have not been studied well. We therefore analyzed 856 patients with Ph/BCR-ABL-positive CML from the German randomized CML-studies I (interferon alpha (IFN) vs hydroxyurea (HU) vs busulfan) and II (IFN+HU vs HU alone). The median observation time was 8.6 years. A total of 503 patients (59%) were male. Female patients were older (51 vs 46 years; P<0.0001), presented with lower hemoglobin (11.7 vs 12.5 g/dl; P<0.0001), higher platelet counts (459 vs 355 x 10(9)/l; P<0.0001), smaller spleen size (3 vs 4 cm below costal margin; P=0.0097), a lower rate of additional cytogenetic aberrations (9 vs 15%; P=0.018) and a less favorable risk profile (P=0.036). The transplantation rate was 14% for female (n=48) and 22% for male patients (n=113). Median survival was longer in female patients (58 vs 49 months; P=0.035) mainly attributable to better survival in the low- and intermediate-risk groups and, independent from risk groups, in the HU group. These results were confirmed by matched-pair analyses based on German population data (n=496, 59 vs 45 months; P=0.0006). This is the first analysis of gender aspects in CML using randomized trials. It demonstrates the relevance of analyses of gender differences in CML and in malignant disease at large.

Cigarette smoking is thought to contribute to carcinogenesis by formation of DNA adducts of tobacco smoke constituents leading to genotoxic damage. The dithiolethione, oltipraz, is a putative cancer chemopreventive agent that induces phase II detoxifying enzymes in preclinical models and reduces aflatoxin adducts in humans living in areas with high dietary levels. To determine if oltipraz could reduce adduct levels of tobacco smoke constituents in the lungs and other target organs, chronic smokers were enrolled to one of three arms: 400 or 200 mg/wk oral oltipraz or placebo. Endobronchial tissue and bronchoalveolar lavage were done before and after 12 weeks of drug treatment; peripheral blood, urine, and oral saline rinse were also collected. Toxicity was assessed every 4 weeks. Fifty-nine of the 77 enrolled subjects completed the study. Of those receiving oltipraz, 15% experienced grade 2/3 toxicity, which was predominantly gastrointestinal. All subject withdrawals occurred in the oltipraz groups. There was no significant difference between pre- and post-polycyclic aromatic hydrocarbon-DNA adduct levels in lung epithelial cells measured by immunoperoxidase staining between treatment and placebo groups. Likewise, no significant differences were found in polycyclic aromatic hydrocarbon or benzo(a)pyrene-7,8-diol-9,10-epoxide adducts measured in blood, oral lining cells, or bladder lining cells. There was also no increase in mRNA or enzymatic activity of phase II enzymes and no change in glutathione levels. Thus, despite moderate drug-related toxicity, there was no significant effect on pharmacodynamic or surrogate risk biomarkers. Other agents with lower toxicity and greater activity to induce phase II enzymes are needed to definitively test the detoxification-induction paradigm in smokers.

To evaluate the effectiveness of gonadotropin-releasing hormone agonists (GnRH-a) with or without coadministration of tibolone in women with menstrual cycle-related irritable bowel syndrome (IBS).

Lymph node status is one of the decisive prognostic factors of breast cancer. Chemotherapy targeting regional lymphatic tissues has emerged as a promising therapy for malignancies with high tendency to disseminate lymphatically. This study was to detect drug concentration in axillary lymph nodes of patients with breast cancer after lymphatic chemotherapy (LC), and to investigate effect of LC on accumulation of antitumor drugs in regional lymph nodes through comparing with the effect of intravenous chemotherapy (VC).

Prolongation of chemotherapy duration, usually referred to as maintenance chemotherapy, has been considered as an approach to improve survival of patients with advanced non-small-cell lung cancer (NSCLC). If the maintenance regimen differs from the induction regimen, patients will receive not only higher total doses of chemotherapy but also earlier delivery of non-cross-resistant agents. We conducted a randomized trial to compare maintenance vinorelbine therapy with observation in previously untreated patients who responded to induction treatment with mitomycin-ifosfamide-cisplatin (MIC).

Although low dietary intakes of antioxidant vitamins and minerals have been associated with higher risks of cancer, results of trials testing antioxidant supplementation for cancer chemoprevention have been equivocal. We assessed whether supplementation with antioxidant vitamins could reduce the incidence of second primary cancers among patients with head and neck cancer.

To determine if granulocyte colony-stimulating factor (G-CSF) with empirical antibiotics accelerates febrile neutropenia resolution compared with antibiotics without it.

Orally disintegrating tablet (ODT) of ondansetron is a new formulation, which instantaneously disintegrates and disperses in the saliva without need for ingestion of a liquid. This makes the formulation suitable for administration in children. The objective of this study was to compare the relative efficacy and cost of ODT and intravenous (IV) formulation of ondansetron in controlling nausea and vomiting in children receiving chemotherapy regimens without cisplatin. This prospective randomized trial was performed in a single institution to compare ODT and IV formulation of ondansetron for the prevention of acute emesis in a group of 22 children. Study agents were administered 30 min before chemotherapy and 12 hourly after chemotherapy (5 mg/m2 IV or 4-8 mg oral according to body surface area in 56 and 39 courses, respectively). After randomization, IV formulation was administered to some children instead of ODT due to unavailability of this formulation. Complete and major control of emesis was obtained in 92% of patients in the IV group and 93% of patients in the ODT group. In 56 courses with grade III-IV emetogenicity, complete response rates were not different between the two treatment arms. In the courses without corticosteroids complete response rates were not also different between the two arms. The mean costs per successfully controlled courses were 121.3 USD for the IV formulation whereas 63.2 USD for the ODT formulation. The results of this study confirmed that ODT formulation of ondansetron is a safe, well-tolerated, and cost-effective antiemetic for children during non-cisplatin-containing moderately and highly emetogenic chemotherapy.

5-HT3 receptor antagonists, including granisetron and ondansetron, are widely used in the prophylactic treatment of chemotherapy-induced nausea and vomiting. Although the cardiac safety of granisetron and ondansetron has been investigated in several adult studies, there is no report investigating the effects of those agents on electrocardiography (ECG) in children. The effects of intravenously infused (over 30 seconds) 0.1 mg/kg ondansetron and 40 microg/kg granisetron on ECG were assessed in 22 children receiving high-dose methotrexate therapy for acute lymphoblastic leukemia. The ECG recording was obtained at before and just after the infusion, and repeated at 1, 3, 6, and 24 hours of treatment. Granisetron administration resulted in a statistically significant decrease of mean heart rate at 1 and 3 hours, and significant prolongation of mean QT and QTc dispersions at 1 hour of infusion. In patients treated with ondansetron, no meaningful change was observed. In conclusion, intravenous granisetron but not ondansetron causes clinically asymptomatic and transient changes on ECG measurements in children receiving high-dose methotrexate therapy.

Surgery remains the standard treatment for glioma, followed by radiotherapy (RT) with or without chemotherapy. Despite multidisciplinary approaches, the median survival time for patients with glioblastoma multiform (GBM) remains at less than 1 year from initial diagnosis. Temozolomide (TMZ), an oral alkylating agent, has shown promising activity in the treatment of malignant gliomas. We conducted a multicenter randomized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM.

This article reports the results of a pooled analysis of six randomized trials conducted to study the efficacy of uracil and tegafur (UFT) in the adjuvant treatment of node-negative breast cancer patients.

Endocrine therapies that profoundly decrease estrogen levels potentially have a detrimental effect on the cardiovascular system. This study evaluated the effect on lipid metabolism of one such agent, the new generation aromatase inhibitor anastrozole, compared with tamoxifen, when used as adjuvant treatment in postmenopausal Japanese women with early breast cancer. All patients had completed primary surgery and were randomized to anastrozole 1 mg once daily (n=22) or tamoxifen 20 mg once daily (n=22). Anastrozole significantly reduced levels of triglycerides and remnant-like particle cholesterol, whereas tamoxifen significantly increased these. Activity of lipoprotein lipase and levels of high-density lipoprotein cholesterol significantly increased after anastrozole treatment. In contrast, activity of hepatic triglyceride lipase, also a key enzyme of triglyceride metabolism, significantly decreased following treatment with tamoxifen. We thus conclude that in our study anastrozole had a beneficial effect on lipid profiles of postmenopausal women with early breast cancer after 12 weeks of treatment.

Oral administration with acyclic retinoid, a synthetic vitamin A analog, for a limited period of 12 months (48 weeks) prevented the development of second primary hepatocellular carcinoma (HCC) and also improved the survival of patients who underwent curative treatments of the initial tumor. Following that randomized controlled study reported in 1996 and 1999, we have continued to follow up the patients by medical imaging and blood chemical analyses, and found that the preventive effect of acyclic retinoid lasted up to 199 weeks after randomization (or 151 weeks after completion of retinoid administration). The retinoid's effect was not mediated by reduction in hepatic necro-inflammation since no significant decrease in serum aminotransferase activity was seen in the retinoid group. Such observation seems quite distinct from the cancer-preventive mechanism of interferon, a potent immunopreventive agent for HCC. We have also shown here the reduction by the retinoid in serum levels of lectin-reactive alpha-fetoprotein (AFP-L3) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), both of which indicate the presence of latent HCC cells. These results suggest that acyclic retinoid may delete such malignant clones before they expand to clinically detectable tumors and thereby inhibited second primary HCC. Once such latent clones are eradicated, it may well take at least several years for the next cancer clone to arise clinically. This may possibly explain a reason for the long-term effect of the retinoid even after the limited period of administration.

Pre-exposure to an environment in which a nausea-inducing body rotation will subsequently be given constitutes a latent inhibition procedure that might act to reduce anticipatory and postrotation nausea.

To study the reasonable dosage for paraplatin according to different dosage calculations.