Little information exists on the functional impact of effective antiemetic protection. In the present study, the Functional Living Index-Emesis (FLIE), was used to assess patient-reported impact of chemotherapy-induced nausea and vomiting (CINV) after administration of a new NK-1 receptor antagonist (aprepitant). Cisplatin-treated patients in a double-blind randomised trial received either aprepitant+dexamethasone+ondansetron on day 1 and aprepitant+dexamethasone on days 2-5 or standard antiemetic therapy (dexamethasone and ondansetron on day 1 and dexamethasone on days 2-5). Emetic events, nausea ratings and rescue medications were recorded in a 5-day diary and the FLIE was completed on day 6. Compared with standard therapy, significantly more patients treated with the high dose aprepitant regimen achieved a Complete Response (71 vs 44%, P<0.001) and also reported no impact on daily life as indicated by the FLIE total score (84 vs 66%, P<0.01). Use of the FLIE demonstrated that improved control of emesis was highly effective in reducing the impact of CINV on patients' daily lives.

ZD9331 is a novel antifolate inhibitor of thymidylate synthase (TS). This multicentre, randomised, phase II/III study compared the efficacy and safety of ZD9331 with gemcitabine in 55 patients with chemonai;ve, locally advanced or metastatic pancreatic cancer. Patients received intravenous (i.v.) ZD9331 (n=30), on days 1 and 8 of a 3-week cycle or i.v. gemcitabine (n=25), once a week for 7 weeks followed by a 1-week rest, then on days 1, 8 and 15 of a 4-week cycle. Objective tumour response and clinical benefit response (CBR) were similar for both groups. More ZD9331 patients were alive at the data cut-off point compared with gemcitabine patients (13 and 8%, respectively). Median survival (152 versus 109 days, respectively) and time to progression (70 versus 58 days, respectively) were longer in the ZD9331 group. Nausea and vomiting (grade 1/2) were the most common toxicities in both groups. These results suggest that, in pancreatic cancer, ZD9331 is equivalent to gemcitabine and may offer a promising alternative to current therapies.

Androgens are involved in the development of prostate cancer. Finasteride, an inhibitor of 5alpha-reductase, inhibits the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate, and may reduce the risk of prostate cancer.

Numerous experimental data have documented the oncostatic properties of melatonin. In addition to its potential direct antitumor activity, melatonin has proved to modulate the effects of cancer chemotherapy, by enhancing its therapeutic efficacy and reducing its toxicity. The increase in chemotherapeutic efficacy by melatonin may depend on two main mechanisms, namely prevention of chemotherapy-induced lymphocyte damage and its antioxidant effect, which has been proved to amplify cytotoxic actions of the chemotherapeutic agents against cancer cells. However, the clinical results available at present with melatonin and chemotherapy in the treatment of human neoplasms are generally limited to the evaluation of 1-year survival in patients with very advanced disease. Thus, the present study was performed to assess the 5-year survival results in metastatic non-small cell lung cancer patients obtained with a chemotherapeutic regimen consisting of cisplatin and etoposide, with or without the concomitant administration of melatonin (20 mg/day orally in the evening). The study included 100 consecutive patients who were randomized to receive chemotherapy alone or chemotherapy and melatonin. Both the overall tumor regression rate and the 5-year survival results were significantly higher in patients concomitantly treated with melatonin. In particular, no patient treated with chemotherapy alone was alive after 2 years, whereas a 5-year survival was achieved in three of 49 (6%) patients treated with chemotherapy and melatonin. Moreover, chemotherapy was better tolerated in patients treated with melatonin. This study confirms, in a considerable number of patients and for a long follow-up period, the possibility to improve the efficacy of chemotherapy in terms of both survival and quality of life by a concomitant administration of melatonin. This suggests a new biochemotherapeutic strategy in the treatment of human neoplasms.

To observe the efficacy of exemestane for postmenopausal advanced metastatic breast cancer, and to assess its side effects.

Methotrexate is postulated to enhance mercaptopurine activation to thioguanine (INN, tioguanine) nucleotides, but the interaction has never been studied in vivo in cancer cells.

Midgut carcinoid tumours often present with widespread disease making curative surgery impossible. Medical treatment therefore plays a major role in the treatment of these patients.

Luteinising hormone releasing hormone (LHRH) analogues are routinely used in the treatment of patients with advanced prostate cancer. This randomised crossover trial was conducted to compare patient comfort and tolerability between two commonly used LHRH analogues: goserelin acetate and leuprorelin acetate. A total of 50 patients were randomised into two groups, each receiving 6-monthly injections of leuprorelin acetate (a liquid presentation) and goserelin acetate (a depot pellet) and crossing over between treatments. Patients completed a simple visual analogue score for the discomfort felt from the injections. An analysis of variance model was used, and the results found that patients do tolerate leuprorelin acetate (0.589) better than goserelin acetate (1.343) (P < 0.001, CI = 95%).

Zevalin (ibritumomab tiuxetan) radioimmunotherapy is a novel treatment for non-Hodgkin's lymphoma (NHL). The Zevalin regimen includes 5 mCi (111)In-labeled Zevalin on Day 1, followed by serial anterior and posterior planar gamma images for imaging or dosimetry. On Day 8, patients receive 0.4 mCi/kg (90)Y Zevalin for radioimmunotherapy. Both Zevalin doses are preceded by 250 mg/m(2) rituximab to clear peripheral B cells and improve biodistribution of the radiolabeled antibody. In a 143-patient, Phase III, randomized study, the Zevalin regimen produced a significantly higher overall response rate than rituximab for relapsed or refractory, low-grade, follicular, or transformed NHL (80% versus 56%, p = 0.02). Fifteen patients from the Zevalin arm of this study were randomly selected for additional radiation dosimetry. (90)Y residence times were calculated from (111)In image analysis data. MIRDOSE3.1 radiation absorbed dose estimates to normal tissues were highest for spleen, testes, and liver, with considerably lower doses reaching heart, lung, intestines, red marrow, and kidneys. Radiation absorbed doses to organs and marrow were within a safe range following administration of 0.4 mCi/kg (90)Y Zevalin.

A phase I study of carboplatin (Paraplatin) administered in two different dosing schedules (single dose every 4 weeks and weekly dosing) in combination with weekly irinotecan (CPT-11, Camptosar) was conducted in patients with relapsed or refractory advanced malignancies. Fifty-three patients with a variety of tumor types were randomly enrolled on the two different treatment regimens and have received a total of 163 cycles of treatment to date. Twenty-six patients received weekly irinotecan in combination with a single fixed dose of every-4-week carboplatin (arm 1). Initially, patients received irinotecan on days 1, 8, and 15, in combination with fixed-dose carboplatin at an area under the concentration-time curve (AUC) of 5.5 (Calvert formula) on day 1 every 28 days. Due to dose-limiting toxicities encountered at the first two dose levels, the protocol was amended to decrease the fixed dose of carboplatin to an AUC of 4.0 every 4 weeks. Dose-limiting toxicity was again encountered, so the day-15 dose of irinotecan was eliminated from the dosing regimen. The recommended phase II dose for heavily pretreated patients is irinotecan at 60 mg/m2 on days 1 and 8 in combination with carboplatin at AUC 4.0 on day 1 with cycles repeated every 28 days. Twenty-seven patients were treated with weekly irinotecan in combination with fixed-dose weekly carboplatin (arm 2). The initial dosing regimen consisted of irinotecan in combination with fixed-dose carboplatin at an AUC of 1.8 on days 1, 8, and 15, with treatment cycles repeated every 28 days. Due to the development of dose-limiting toxicities at the first two dose levels, the dosing regimen was subsequently amended to weekly irinotecan in combination with fixed-dose carboplatin at AUC 2.0 on days 1 and 8 only, and the dosing interval was shortened to every 21 days. With this amended regimen, the recommended phase II doses are irinotecan at 90 mg/m2 in combination with carboplatin at AUC 2.0 on days 1 and 8, with treatment cycles repeated every 21 days.

We performed a multicentre randomised trial to compare the efficacy and toxicity of 12 weeks of 5-fluorouracil (5-FU) delivered by protracted intravenous infusion (PVI 5-FU) against the standard bolus regimen of 5-FU and folinic acid (5-FU/FA) given for 6 months as adjuvant treatment in colorectal cancer. A total of 716 patients with curatively resected Dukes' B or C colorectal cancer were randomised to 5-FU/FA (5-FU 425 mg m(-2) i.v. and FA 20 mg m(-2) i.v. bolus days 1-5 every 28 days for 6 months) or to PVI 5-FU alone (300 mg m(-2) day for 12 weeks). With a median follow-up of 19.8 months, 133 relapses and 77 deaths have been observed. Overall survival did not differ significantly (log rank P=0.764) between patients receiving 5-FU/FA and PVI 5-FU (3-year survival 83.2 vs 87.9%, respectively). Patients in the 5-FU/FA group had significantly worse relapse-free survival (RFS, log rank P=0.023) compared to those receiving PVI 5-FU (3-year RFS, 68.6 vs 80%, respectively). Grades 3-4 neutropenia, diarrhoea, stomatitis and severe alopecia were significantly less (P<0.0001) and global quality of life scores significantly better (P&<0.001) for patients in the PVI 5-FU treatment arm. In conclusion, infused 5-FU given over 12 weeks resulted in similar survival to bolus 5-FU and FA over a 6 month period, but with significantly less toxicity.

The treatment of advanced melanoma is still disappointing. In a multicenter randomized clinical trial to compare a chemotherapy (CT) with or without low doses of IL-2 and IFN (Bio-CT), the participating centers chose whether or not to add a nitrosourea, carmustine (BCNU) to the therapy. The aim of the present paper is to report the clinical results of the patients (pts) treated in both arms with BCNU. One hundred and seventy-six pts with advanced melanoma were enrolled in the study from 27 centers and a total of 18 pts also received BCNU in 3 centers. No further changes to the protocol criteria were allowed. One patient refused the treatment. No complete responses were observed. Irrespectively of the treatment arm, 9/17 pts showed a partial response to therapy (53%) (5/9 in the CT and 4/8 in the BioCT arm). The most important adverse events observed were hematological: 12 pts presented grade 3 (6 pts) or grade 4 (6 pts) leukocytopenia and 9 pts had grade 4 thrombocytopenia, all of which resolved spontaneously. The addition of a nitrosourea to CT or Bio-CT appears to improve response rates compared to the same regimens without nitrosourea. Patient tolerability is acceptable. Further studies using this combination are warranted.

Aprepitant is a novel neurokinin 1 (NK(1)) antagonist that has been shown to improve control of chemotherapy-induced nausea and vomiting (CINV) when added to a standard antiemetic regimen of a 5-hydroxytriptamine-3 antagonist plus a corticosteroid. The authors sought to evaluate further the efficacy and tolerability of aprepitant plus standard therapy in a large clinical trial.

The purpose of this study was to assess whether the administration of recombinant human erythropoietin (rHuEPO) would correct anemia and improve the quality of life (QOL) in cancer patients receiving chemotherapy. One hundred twenty-two patients with hemoglobin </=11.0 g/dl were randomized to receive rHuEPO 10,000 U three times weekly (n = 61) or no additional treatment (n = 61). Response was assessed by measuring changes in hemoglobin level and QOL. QOL was evaluated before each cycle of chemotherapy at baseline, Week 4, and Week 12 using two separate self-report questionnaires. The analyses indicated that the rHuEPO-treated patients experienced significantly less fatigue (P < 0.05) than their control group counterparts, and reported significantly higher scores on energy level (P < 0.05), ability to perform daily activities (P < 0.01), and overall QOL (P< 0.05). The overall change in hemoglobin level was significantly greater in the rHuEPO group than in the control group (1.7 g/dl versus 0.3 g/dl, P < 0.001). rHuEPO effectively corrects anemia and significantly improves QOL in patients with solid tumors receiving chemotherapy.

Quality of life (QOL) outcomes in patients with chronic myeloid leukemia (CML) were evaluated in an international phase III study.

Doxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug. A large-scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7% of patients developed doxorubicin-related congestive heart failure (CHF) after a cumulative dose of 550 mg/m(2). To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting, the authors evaluated data from three prospective studies to determine both the incidence of doxorubicin-related CHF and the accumulated dose of doxorubicin at which CHF occurs.

In two large, randomized prevention trials, supplementation with beta-carotene increased the risk of lung cancer. Subjects in these studies were predominantly cigarette smokers, and the adverse effects were concentrated among those who also drank alcohol. Although beta-carotene supplementation appeared not to increase the risk of cancer generally, it is not clear if smoking and/or alcohol use alters the effect of beta-carotene on carcinogenesis at sites outside the lung.

Tamoxifen has been the gold standard adjuvant therapeutic agent for postmenopausal women with hormone-sensitive breast cancer for > 25 years. Although it continues to play an important role in treating premenopausal women, tamoxifen's association with some serious safety and tolerability issues, including increased incidence of endometrial cancer and thromboembolic events, may be cause to limit its use in postmenopausal women. Anastrozole was the first drug to show improved efficacy and safety compared with standard therapies for first- and second-line therapy of hormone-sensitive advanced breast cancer in postmenopausal women. This article provides a review of the results of the first major analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) early-stage breast cancer trial, initiated in 1996, and discusses the implications for the use of anastrozole in the adjuvant setting. This randomized, double-blind, multicenter trial compared tamoxifen (20 mg once daily) with anastrozole (1 mg) alone and in combination with tamoxifen, as adjuvant endocrine treatment for postmenopausal patients with operable, invasive, early-stage breast cancer. The results of the ATAC trial show anastrozole to be more effective and better tolerated than tamoxifen in this group of patients, and an updated follow-up suggests the therapeutic index for anastrozole will continue to remain superior to that of tamoxifen. Anastrozole is now emerging as a new standard for the adjuvant treatment of postmenopausal women with hormone-sensitive early-stage breast cancer. New adjuvant trials are currently using anastrozole in the control arm.

It has been demonstrated that the hematopoiesis is under a neuroendocrine control, namely mediated by the pineal gland. The pineal indole melatonin (MLT) has appeared to exert thrombopoietic and lymphopoietic activity, whereas it has no relevant effect on red cell differentiation. The present study was performed to evaluate the influence of another pineal indole, the 5-methoxytryptamine (5-MTT) on red cell line and hemoglobin production.