9-Cis-retinoic acid (aliretinoin) is a pan-retinoid receptor agonist and has been demonstrated in preclinical models to have potent chemoprevention effects. The purpose of this study was to determine the utility of using aliretinoin as a chemoprevention agent in cervical dysplasia. Patients with histological evidence of cervical intraepithelial neoplasia (CIN) 2/3 were randomized in a double-blind manner to receive high-dose aliretinoin (50 mg), low-dose of aliretinoin (25 mg), or placebo daily for 12 weeks. Compliance and side effects were monitored at various time points during therapy. At the completion of therapy, all of the patients underwent a loop procedure. Histology of pretreatment biopsies was compared with that of loop specimens. One-hundred and fourteen patients with CIN 2/3 were enrolled in the study. In the 112 patients evaluable for toxicity, headache was the most common clinical side effect and was experienced more frequently (74%) in the high-dose aliretinoin group. Eight patients withdrew from the study before completion of study medication because of unacceptable side effects. In the 104 patients evaluable for efficacy, there was no statistical difference in the rate of regression among the placebo (32%), the low-dose aliretinoin (32%), and the high-dose aliretinoin (36%) groups. (P = not significant; power 0.06). Aliretinoin at these dosages and this schedule does not appear to result in significant regression rates in CIN 2/3 patients when compared with placebo. Headache is encountered frequently and may thwart efforts to increase the dose or duration of aliretinoin in future cervical cancer chemoprevention studies. The rate of histological regression in biopsied CIN 2/3 patients is high even over a short time interval, and emphasizes the importance of having a placebo arm and an adequate sample size in cervical dysplasia chemoprevention studies.

Loss of retinoic acid receptor beta (RAR-beta) expression in the bronchial epithelium is considered a biomarker of preneoplasia. Retinoids can restore expression of this receptor and, presumably, halt the progression of carcinogenesis. This study was designed to investigate whether either of two retinoid-based regimens, 9-cis-retinoic acid (RA) or 13-cis-RA plus alpha-tocopherol (AT), could reverse RAR-beta expression loss in former smokers after 3 months of treatment.

Aim of this study was to characterize the difference in pharmacokinetics (PK) of paclitaxel (PAC) after 1-h and 3-h infusion in humans and to define a pharmacodynamic relationship between PAC PK and myelotoxicity.

Health-related quality of life (HrQOL) assessments are gaining importance as outcome measures in cancer clinical trials. A recently published clinical trial reported statistically significant (P<0.001) increases in haemoglobin (Hb) levels and significantly (P<0.01) increased HrQOL scores following the administration of recombinant human erythropoietin (r-HuEPO, epoetin alfa) versus placebo to anaemic cancer patients who received non-platinum chemotherapy. This study employed five cancer-specific HrQOL instruments. Hb and HrQOL data from this trial were analysed to estimate the minimally important difference (MID) in HrQOL measures that could be interpreted as clinically meaningful, with Hb level selected as the best external standard. Patients were assigned to two groups: improved (Hb increases of >/=1 g/dL) or stable (change in Hb of-1 g/dL to <1 g/dL). The MID was first determined as the difference between the mean changes in HrQOL in the improved group versus the stable group. By this analysis, the differences in HrQOL scores between the epoetin alfa group and the placebo group were clinically important for all Hb-sensitive, cancer-specific HrQOL evaluations. Linear regression analyses performed to provide estimates of the MID for specific values of Hb change confirmed that the differences in HrQOL scores between patient groups were clinically significant. These analyses were repeated using a data set from a separate clinical trial, which further supported the conclusion that observed HrQOL changes demonstrated in the multicentre, double-blind study were clinically important. These methods provide one means for interpreting the clinical relevance of changes in HrQOL evaluated in clinical trials.

More efficacious and safer hormonal agents are needed for breast cancer treatment and prevention. Idoxifene is a novel selective estrogen receptor modulator (SERM) that, in preclinical models, has greater antiestrogenic but lower estrogenic activity than tamoxifen.

To examine the development of antiandrogen-induced gynecomastia and breast tenderness in the first 253 patients in a randomized Scandinavian trial (SPCG-7/SFUO-3) with a 12-month complete follow-up evaluation performed by both doctors and patients.

Osteoprotegerin (OPG) is a decoy receptor for OPG ligand (OPGL), or receptor activator of NF-kappaB ligand (RANKL). RANKL/RANK interaction is important in terminal differentiation and activation of osteoclasts. In binding to RANKL, OPG blocks differentiation and activation of osteoclasts. AMGN-0007 is a recombinant OPG construct developed as a potential therapeutic agent in the treatment of bone disease.

The effect of different dose intensities of 5-fluorouracil (5-FU) in advanced colorectal cancer was investigated. A total of 312 patients were randomized to receive 400 mg/m2 (group A), 500 mg/m2 (group B) or 600 mg/m2 (group C) of 5-FU with leucovorin 60 mg/m2 on two consecutive days every second week. Treatment continued to progression. Pharmacokinetic analyses with calculation of the area under the concentration (AUC) were performed in 91 patients. The primary endpoint was survival, and secondary endpoints were time to disease progression, toxicity and, if the disease was measurable, tumour response. The study was well balanced in the three groups with respect to a number of patient characteristics. Crude survival as estimated by Kaplan-Meier plots was not statistically significantly different (p = 0.07) but tended to show the best results in the intermediate dose group (median survival 10, 12.5 and 10 months, respectively). Analyses of time to progression or death showed significant differences among the three groups (p = 0.02) with the longest progression-free interval in the intermediate group receiving 500 mg/m2. The objective response rates were 23%, 39% and 28%, respectively (p = 0.02). The actual/projected dose intensity (mg/m2/week) was 92%, 92% and 84%, respectively. AUC did not correlate with response or survival. The frequency of severe side effects in group C was significantly higher than that of groups A and B. The study indicated that an increase from 800 to 1000 mg/m2 of bolus 5-FU fortnightly improved the treatment results but a further increase only worsened the toxicity.

Conventional therapy for childhood acute lymphoblastic leukemia (ALL) includes prednisone and oral 6-mercaptopurine. Prior observations suggested potential advantages for dexamethasone over prednisone and for intravenous (IV) over oral 6-mercaptopurine, which remain to be validated. We report the results of a randomized trial of more than 1000 subjects that examined the efficacy of dexamethasone and IV 6-mercaptopurine. Children with National Cancer Institute standard-risk ALL were randomly assigned in a 2 x 2 factorial design to receive dexamethasone (6 mg/m(2)/d) for 28 days in induction, plus taper, compared with prednisone (40 mg/m(2)/d). The second randomized assignment was for daily oral or weekly IV 6-mercaptopurine during consolidation. During maintenance, 5 days of the randomized steroid was given monthly, at the same dose, and all patients received daily oral 6-mercaptopurine. During delayed intensification, all patients received a dexamethasone dosage of 10 mg/m(2)/d for 21 days, with taper. Intrathecal (IT) methotrexate was the sole central nervous system-directed therapy. Patients randomly assigned to receive dexamethasone had a 6-year isolated central nervous system-relapse rate of 3.7% +/- 0.8%, compared with 7.1% +/- 1.1% for prednisone (P =.01). There was also a trend toward fewer isolated bone marrow relapses with dexamethasone. The 6-year event-free survival (EFS) was 85% +/- 2% for dexamethasone and 77% +/- 2% for prednisone (P =.002). EFS was similar with oral or IV 6-mercaptopurine; however, patients assigned to IV 6-mercaptopurine had decreased survival after relapse.

A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of a sucralfate mouthwash in preventing and alleviating oral mucositis induced by 5-fluorouracil (5FU). A total of 81 patients with colorectal cancer were enrolled. Patients were studied during their first cycle of chemotherapy with 5FU and leucovorin (LV) daily for 5 days every 4 weeks (Mayo Clinic schedule). Patients were randomly allocated to receive either a sucralfate suspension or a placebo suspension that was identical in appearance. Patients were instructed to use the suspension as a mouthwash four times daily from the beginning of the chemotherapy cycle. All patients received oral cryotherapy. Patients graded the severity of their own symptoms on a daily basis, and this was the primary outcome measure. There was no difference in the frequency or severity of oral mucositis between the sucralfate- and the placebo-treated group. Some mucositis was reported by 79% of the patient group. Assessment of mucositis by trial staff underestimated the incidence of this problem. Results of this trial do not support the hypothesis that a sucralfate mouthwash can prevent or alleviate oral mucositis induced by 5FU. Patient reporting of mucositis is a more sensitive instrument for assessment of mucositis than review by medical staff.

Despite dose calculation using body-surface area (BSA), pharmacokinetics of most anticancer drugs show wide interindividual variability. In this study, we evaluated the role of BSA in paclitaxel disposition.

The aim of this study was to observe the efficacy and the side effects of nedaplatin in treatment of non-small cell lung cancer (NSCLC).

In this prospective, randomized, double-blind study, we evaluated the effects of tibolone therapy in association with preoperative gonadotropin releasing hormone agonist (GnRHa) therapy on the reduction of myoma volume. Twenty patients with myoma uteri were divided into two groups. Group I was given monthly triptoreline (3.75 mg every 28 days IM) treatment for six months. As for group II, tibolone was added on to this treatment. For all of the patients, physical examinations, pelvic ultrasonography, and hormone analyses were carried out and the myoma volume was measured by ultrasonography. The patients were called every month and physical examination, ultrasonography and hormone analyses were repeated. Side-effects were recorded. The SPSS/PC 6.0 program was used for statistical analysis. Statistical significance was defined as a p < 0.05. The results are expressed as means +/- SD. While the average volume of myoma was 72.97 +/- 68.5 cm3 in group I, 78.83 +/- 74.1 cm3 in group II before treatment; it was reduced to 29.91 +/- 27.8 cm3 in group I at the end of six months of treatment. Reductions of 59.6% in group I and 63.9% in group II were determined, however the difference was not statistically significant (p > 0.05). At the beginning the level of serum estradiol was 65.4 +/- 22.3 pg/ml in group I which decreased to 37.2 +/- 4.2 pg/ml by the end of the first month. Amenorrhea occurred in six patients after the second injection and four patients after the third injection in group I. Whereas the level of estradiol was 60.9 +/- 19.5 pg/ml in group II at the beginning, it was reduced to 40.5 +/- 6.2 pg/ml by the end of the first month. Amenorrhea occurred in four patients after the second injection and four patients after the third injection in group II. In group I the patients had the problem of flushing (80%), vaginal dryness (50%), and night sweats (30%). In group II these rates were 30%, 20%, and 20%, respectively. Triptoreline is a GnRHa which has been found to be effective in reducing myoma volume, but this effect could not be deactivated with tibolone. However, a decrease was observed in the side-effects resulting from hypoestrogenism.

To compare fluorouracil (FU) alone with FU plus cisplatin (FP) and with uracil and tegafur plus mitomycin (UFTM) for patients with advanced gastric cancer in a prospective, randomized, controlled trial.

The efficacy and safety of a new 0.5% fluorouracil topical cream were compared with vehicle control for the treatment of actinic keratosis (AK). Active treatment applied once daily for 1, 2, or 4 weeks was more effective than vehicle control in achieving reduction from baseline in lesion counts and lesion clearance. Active treatment also resulted in significantly better global assessments of overall improvement. Treatment was effective regardless of the number of baseline lesions. Although longer treatment duration correlated with greater efficacy, treatment for 1, 2, or 4 weeks was effective. This new microsphere-based fluorouracil formulation was generally well tolerated; adverse events were primarily limited to facial irritation that resolved quickly after treatment. This new treatment provides a safe alternative to the topical fluorouracil formulations currently available for the 1-, 2-, or 4-week treatment of AK.

The objective of the study was to develop and validate a population pharmacokinetic model for irinotecan and 2 of its metabolites, SN-38 and SN-38 glucuronide (SN-38G).

Adjuvant combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil plus vincristine and prednisone (CMFVP) was compared with single-agent L-phenylalanine mustard (L-PAM) for the treatment of patients with axillary lymph node positive primary breast carcinoma over 20-years of follow-up.

Docetaxel (Taxotere) is a potent anticancer agent, with proven efficacy as first-line therapy in non-small-cell lung cancer (NSCLC). The aim of this large randomised multicentre phase III study was to evaluate docetaxel in the neoadjuvant (pre-operative) setting.

To compare the efficacy, safety and tolerability of letrozole, an advanced non-steroidal aromatase inhibitor, and fadrozole hydrochloride, an older-generation drug in this class, we conducted a randomised double-blind trial in postmenopausal women with advanced breast cancer.

To evaluate the efficacy and safety of nausea oral, disintegrating buccal tablet (DBT) in the prevention of gastrointestinal reaction induced by anticancer drugs (cisplatin DDP 30 - 50 mg/m(2) or adramycin ADM >/= 40 mg/m(2)), as compared with those of kytril tablets.