To determine the effect of estrogen (E) alone (without the influence of testosterone (T)) on cognitive function in older men, using 17-beta micronized estradiol versus placebo in older men rendered hypogonadal (low T and E) by treatment for prostate cancer.

Radiochemotherapy (RCT) is an effective treatment for locally advanced non-small cell lung cancer, but can be limited by acute and late toxicities (esophagitis, pneumonitis, and myelosuppression). This trial investigated whether pretreatment with amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD), a radioprotector, could reduce the incidence of RCT-induced acute and late toxicities. Between October 1997 and August 1999, 73 patients with previously untreated stage IIIa-IIIb non-small cell lung cancer were randomized to treatment with RCT alone or RCT plus amifostine (300 mg/m(2) daily intravenous infusion). Chemotherapy consisted of either paclitaxel (60 mg/m(2)) or carboplatin (area under the concentration-curve of 2) once weekly during a 5- to 6-week course of conventional radiotherapy given as 2 Gy daily fraction, 5 days a week to a total dose of 55 to 60 Gy. Esophagitis and acute lung toxicity were evaluated during treatment; late lung toxicity was assessed at 3 and 6 months after RCT and was graded from 0 to 4 according to the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer criteria. Esophageal endoscopy was performed the fourth week during RCT and 1 month after the end of RCT. Endoscopic findings of radiation esophagitis were scored from 0 to 3. There was no significant difference between treatment arms in baseline patient characteristics. A total of 68 patients were evaluable for toxicity and efficacy (RCT group, n = 32; RCT plus amifostine, n = 36). The incidence of grade >or= 3 esophagitis during RCT was significantly lower for patients receiving amifostine than for those receiving RCT alone (38.9% v 84.4%; P <.001). The incidence of grade >or= 3 acute pulmonary toxicity was also significantly reduced in amifostine-treated patients (19.4% v 56.3%; P =.002). At 3 months following RCT, patients treated with amifostine had a significantly lower incidence of pneumonitis than those who received RCT alone (P =.009). Endoscopic grade >or= 2 esophagitis was observed in eight of 15 patients in the RCT group and in three of 18 patients in the RCT plus amifostine group (P =.061). No significant differences in response rates were noted between patients receiving RCT with or without amifostine (P =.498). Amifostine is effective in reducing the incidence of both acute and late toxicities associated with RCT in patients with locally advanced non-small cell lung cancer without compromising antitumor efficacy.

Idoxifene is a novel selective oestrogen receptor modulator (SERM) which had greater binding affinity for the oestrogen receptor (ER) and reduced agonist activity compared with tamoxifen in preclinical studies. In a randomized phase II trial in 56 postmenopausal patients with progressive locally advanced/metastatic breast cancer we assessed whether idoxifene showed evidence of activity compared with an increased 40 mg/day dose of tamoxifen in patients who had previously demonstrated resistance to the standard 20 mg/day dose of tamoxifen. Of 47 patients eligible for response (25 idoxifene, 22 tamoxifen), two partial responses and two disease stabilizations (SD) for >6 months were seen with idoxifene (overall clinical benefit rate 16%, 95% CI 4.5-36.1%). The median duration of clinical benefit was 9.8 months. In contrast, no objective responses were seen with the increased 40 mg/day dose of tamoxifen, although two patients had SD for 7 and 14 months (clinical benefit rate 9%, 95% CI 1.1-29.2%). Idoxifene was well tolerated and the reported possible drug-related toxicities were similar in frequency to those with tamoxifen (hot flushes 13% vs 15%, mild nausea 20% vs 15%). Endocrine and lipid analysis in both groups showed a similar significant fall in serum follicle-stimulating hormone and luteinizing hormone after 4 weeks, together with a significant rise in sex hormone binding globulin levels and 11% reduction in serum cholesterol levels. In conclusion, while idoxifene was associated with only modest evidence of clinical activity in patients with tamoxifen-resistant breast cancer, its toxicity profile and effects on endocrine/lipid parameters were similar to those of tamoxifen.

A prospective randomized study was conducted in our department of Radiotherapy, Regional Institute of Medical Sciences, Imphal to evaluating the role of chemoradiation in the management of advanced inoperable cervical cancer (stage IIB-IIIB) taking only radiation treatment as control spanning the period 1996-1999. Of the fifty patients accumulated in the study group, three patients did not complete treatment, one expired due to other causes and three were lost to follow up. Likewise, of the forty-six patients in the control group, one patient did not complete treatment and 4 were lost to follow up. Thus only 43 and 41 patients were available for the result analysis for the study and control groups respectively. The early treatment response as assessed after two months of treatment conclusion were 79.1%, 13.9%, 93.0% and 58.5%, 31.7%, 90.2% as complete response (CR), partial response (PR), and total response (TR) respectively for the study and control groups. Our patients included in this study had a median follow up of 35 months and 33 months for study and control groups respectively. For this follow up, the disease-free survival, survival with disease and overall survival were 67.4%, 7.0%, 74.4% and 43.9%, 12.2%, 56.1% for study and control groups respectively. There was an increase in early side-effects in the chemoradiation group but the difference was not significant. Because of the early side effects, treatment delays ensued in 7 patients (16.3%) and in 3 patients (7.3%) in the study and control groups respectively. There was no significant increase in the late treatment toxicities in both the groups.

Ovarian cancer is the most frequent cause of death due to gynecologic malignancy in both the United States and in Europe. A phase III investigation compared second line treatment Caelyx with topotecan in patients with advanced epithelial ovarian carcinoma who failed a first-line platinum-containing regimen. A total of 474 patients were enrolled Although no significant advantage of Caelyx over topotecan with regards to overall survival and progression was found, there were fewer adverse events in the Caelyx arm and Caelyx had significantly better quality of life profile. We conducted a cost minimization analysis of both treatment arms. Costs were estimated from the viewpoint of the hospital, over the duration of the study period (12 weeks). The frequency of adverse events was derived from the trial's CRF, the treatment patterns of adverse events was estimated for each type of adverse event and each grade for a given type of adverse event. Costs included that of the drug and management of adverse events. Because of uncertainty on actual time spent in French hospitals, administration costs were not valued. Adverse events valued in the analysis were: stomatitis/ pharyngitis, PPE, nausea/vomiting diarrhea, anemia, thrombocytopenia, neutropenia, sepsis, fever. Drug costs and costs of blood products were valued using the purchase price by the hospital, costs of tests and hospital days were estimated from the hospital's accounting system. The drug cost per patient was 8,735 euros for Caelyx and 6,196 euros for topotecan, the cost of adverse events were 528 and 3,632 euros for Caelyx and topotecan respectively, due to the high rate of adverse events in patient treated with topotecan. The total costs were 9,279 and 9,938 for Caefyx and topotecan respectively.

To compare the efficacy and safety of ramosetron and granisetron in prevention of gastrointestinal reaction induced by cisplatin or adramycin.

To evaluate the efficacy of TACE (transcatheter arterial chemoembolization) with use of low-dose versus conventional-dose anticancer drugs in hepatocellular carcinoma patients with cirrhosis and to analyze their prognostic factors.

It is important to get high quality autologous peripheral blood stem cell (APBSC) for successful peripheral blood stem cell transplantation. Cyclophosphamide (CTX) plus recombined human granulocyte colony-stimulating factor (rhG-CSF) is standard regimen for APBSC mobilization. Etoposide plus rhG-CSF is another regimen for mobilization in recent years. The purpose of this study was to observe and compare the effects of these two regimens in APBSC mobilization for the patients with malignant lymphoma and germ cell tumors.

Intrinsic estrogenicities of the selective estrogen receptor modulators (SERMs) toremifene 60 mg daily or 200 mg daily and tamoxifen 20 mg daily (TOR60, TOR200 and TAM20) were compared in a randomized clinical study in postmenopausal women with advanced breast cancer. The study was open label in three parallel groups. Variables for analysis were serum follicle stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin (SHBG), estradiol (E2), antithrombin III (AT III), aspartate aminotransferase (ASAT) and vaginal cytology. Clinical efficacy and safety have been reported earlier. A total of 648 patients were randomized (221 to TOR60, 212 to TOR200 and 215 to TAM20). Sera were available for the analysis from 148, 165 and 156 and for vaginal cytology from 98, 93 and 86 patients, respectively. All treatment regimens showed tissue-specific and dose-dependent estrogen agonist effect. In the primary measure of in vivo estrogenicity, effect on hypothalamus-pituitary-axis, all three treatment regimens decreased serum FSH (p < 0.001). TOR200 was more potent than the two other treatments (p < 0.05), but surprisingly, TAM20 was more estrogenic than TOR60 (p < 0.001). As could be expected in postmenopausal women, the treatments had no effect on mean serum E2 concentrations and decrease of serum LH was similar to that of FSH. Estrogenic effect on the liver was seen as dose-dependent increase of SHBG with statistically significant differences between the treatment groups (p < 0.001). Trends of transient ASAT elevations in TOR200 group (p = 0.07) and in all treatment groups AT III decrease (p = 0.1) were seen in the beginning of the treatment. TOR60 or TAM20 did not have an effect on mean ASAT values, and AT III decreased in TAM20 group more than in the two other groups (p = 0.1 compared to TOR60 and p < 0.05 compared to TOR200). Estrogenic effects on vaginal superficial cells were higher in TOR60 and TOR200 groups when compared to TAM20 (p < 0.05). Toremifene and tamoxifen had tissue-specific and partially dose-dependent estrogenic effects in hypothalamus-pituitary-axis, in the liver and in the vaginal epithelium of postmenopausal women. In some tissues tamoxifen 20 may be more estrogenic than toremifene 60 mg/day.

Treatment with zoledronic acid (Zol) was compared with a dose of 90 mg of pamidronate (Pam) in breast carcinoma (BC) patients with at least 1 osteolytic lesion based on data from a Phase III, randomized trial.

Although chemotherapy and ovarian function suppression are both effective adjuvant therapies for patients with early-stage breast cancer, little is known of the efficacy of their sequential combination. In an International Breast Cancer Study Group (IBCSG) randomized clinical trial (Trial VIII) for pre- and perimenopausal women with lymph node-negative breast cancer, we compared sequential chemotherapy followed by the gonadotropin-releasing hormone agonist goserelin with each modality alone.

We have continued to monitor the survival of patients randomised in a previously reported multicentre phase III study of topotecan versus paclitaxel in patients with advanced epithelial ovarian cancer who had failed one prior platinum-based regimen.

A prospective randomized clinical trial was implemented to assess whether the concomitant or the sequential addition of tamoxifen to chemotherapy provides improved clinical benefit in the adjuvant treatment of breast cancer in postmenopausal patients.

To evaluate the efficacy and safety of treatments for advanced non-small-cell lung cancer in elderly patients aged 75 years or older, we conducted a phase II study of cisplatin and docetaxel administered in three consecutive weekly infusions.

The survival benefit associated with first-line chemotherapy in advanced lung cancer led to the need for second-line chemotherapy. Docetaxel (Taxotere) has proven efficacy in both settings. This study evaluated the safety and efficacy of two doses of docetaxel in patients with non-small-cell lung cancer who had failed first-line platinum-based chemotherapy.

Trastuzumab provides significant clinical benefits in HER2-positive metastatic breast cancer patients when administered in combination with chemotherapy. Chemotherapy has also been shown to be beneficial in some patients with advanced non-small-cell lung cancer (NSCLC). The present randomized phase II trial examined the effect of adding trastuzumab to a standard chemotherapeutic combination (gemcitabine-cisplatin) in patients with HER2-positive NSCLC.

A prospective randomized trial was conducted to study the timing of high-dose intravenous melphalan and autologous stem cell transplantation (HDM/SCT) in AL amyloidosis. In all, 100 newly diagnosed patients were randomized to receive HDM/SCT, either as initial therapy (Arm-1) or following two cycles of oral melphalan and prednisone (Arm-2). The objectives of the trial were to compare survival and hematologic and clinical responses. With a median follow-up of 45 months (range 24-70), the overall survival was not significantly different between the two treatment arms (P=0.39). The hematologic response and organ system improvements after treatment did not differ between the two groups. Fewer patients received HDM/SCT in Arm-2 because of disease progression during the oral chemotherapy phase of the study, rendering them ineligible for subsequent high-dose therapy. This affected patients with cardiac involvement particularly, and led to a trend for an early survival disadvantage in Arm-2. Hence, newly diagnosed patients with AL amyloidosis eligible for HDM/SCT did not benefit from initial treatment with oral melphalan and prednisone, and there was a survival disadvantage for patients with cardiac involvement if HDM/SCT was delayed by initial oral chemotherapy.

Serotonin receptor antagonists are recommended by the American Society of Clinical Oncology for the prevention of acute and delayed chemotherapy-induced emesis. However, the most effective agent in this class of antiemetic drugs for preventing emesis has not been clearly defined. We therefore performed a double-blind, crossover, randomized, controlled trial comparing the efficacy of granisetron and ramosetron, using patient preference as the primary endpoint.

To evaluate low-dose extended duration interferon alfa-2a as adjuvant therapy in patients with thick (> or = 4 mm) primary cutaneous melanoma and/or locoregional metastases.

To establish whether the combination of a corticosteroid (dexamethasone) and the newer serotonin-3 (5-HT(3)) receptor antagonist ramosetron is superior to ramosetron alone in controlling cisplatin-induced emesis.