Randomized trial of intravenous iron supplementation in patients with chemotherapy-related anemia without iron deficiency treated with darbepoetin alpha.

PURPOSE: Unresponsiveness to erythropoiesis-stimulating agents, occurring in 30% to 50% of patients, is a major limitation to the treatment of chemotherapy-related anemia. We have prospectively evaluated whether intravenous iron can increase the proportion of patients with chemotherapy-related anemia who respond to darbepoetin. PATIENTS AND METHODS: Between December 2004 and February 2006, 149 patients with lung, gynecologic, breast, and colorectal cancers and >or= 12 weeks of planned chemotherapy were enrolled from 33 institutions. Patients were required to have hemoglobin or= 12 g/dL or >or= 2 g/dL increase). RESULTS: Hematopoietic response by intention-to-treat analysis was 76.7% (95%CI, 65.4% to 85.8%) in the darbepoetin/iron group and 61.8% (95%CI, 50.0% to 72.7%) in the darbepoetin group (P = .0495). Among patients fulfilling eligibility criteria and having received at least four darbepoetin administrations, hematopoietic responses in the darbepoetin/iron group (n = 53) and in the darbepoetin-only group (n = 50) were 92.5% (95% CI, 81.8% to 97.9%) and 70% (95% CI, 55.4% to 82.1%), respectively (P = .0033). Increase of hemoglobin during treatment period showed a time profile favoring darbepoetin/iron with statistically significant effect from week 5 on. The safety profile was comparable in the two arms. CONCLUSION: In patients with chemotherapy-related anemia and no iron deficiency, IV iron supplementation significantly reduces treatment failures to darbepoetin without additional toxicity.

Randomised, open-label, phase II trial of paclitaxel, gemcitabine and cisplatin versus gemcitabine and cisplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium.

The purpose of the study was to evaluate the antitumor activity and the safety of paclitaxel combined with gemcitabine and cisplatin in patients affected by advanced transitional cell carcinoma of the urothelium (TCC). Eighty-five patients affected by advanced TCC and measurable disease were randomized to receive either paclitaxel at dosage of 70 mg/m2, gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks (GCP) or gemcitabine 1000 mg/m2 on days 1, 8, 15 and cisplatin 70 mg/m2 on day 2 every 4 weeks (GC). All enrolled patients were considered evaluable for response and toxicity (intention to treat). The observed response rate was 43% for GCP and 44% for GC combination, respectively. Median time to treatment failure was 32 weeks for GCP and 26 weeks for GC and overall survival 61 vs 49 weeks, respectively (p-value not significant). Grade 3-4 neutropenia was observed in 49% of patients treated with GCP vs 35% of those treated with GC (P=0.05) and grade 3-4 thrombocytopenia was observed in 36% of GCP treated patients as compared to 21% of those treated with GC (P=0.01). Seven patients over 70 years old or with poor PS were removed from the study: 6 patients from GCP group (2 toxic deaths, 2 grade 4 myelotoxicity and 2 grade 3 asthenia) and 1 from GC group was lost to follow-up after the first cycle. The combination of paclitaxel, gemcitabine and cisplatin is effective in the treatment of TCC. However, the addition of paclitaxel to the combination of gemcitabine plus cisplatin seems to increase toxicity, therefore it seems not suitable for poor PS patients and those over 70 years old. Larger and more powered studies are needed to exactly define the role of paclitaxel in this combination.

A phase I study of capecitabine in combination with vinorelbine in advanced breast cancer.

A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the combination of vinorelbine and capecitabine in patients affected with metastatic breast cancer. Eighteen patients with histologically confirmed advanced breast cancer, who had failed =1 prior chemotherapy regimen, were enrolled. The median age was 56 years (range, 39-70 years). All but 1 had previously received a combination of anthracyclines and taxanes; performance status (Eastern Cooperative Oncology Group) was 0/1 or 2 in 13 and 5 patients, respectively. Vinorelbine was administered at a fixed dosage of 25 mg/m2 on days 1 and 8 every 3 weeks. Capecitabine was administered orally, at an escalated dose ranging from 1400 mg/m2 to 2250 mg/m2 for 14 consecutive days starting on day 1 of the cycle, divided into 2 daily doses delivered half an hour after eating at 12-hour intervals. Three patients were treated at each dose level: if 1 patient developed a DLT, an additional 3 patients were treated at the same dose level. If 2 additional patients experienced DLT, no further escalation was allowed and the previous dose level was declared MTD. Dose-limiting toxicity was reached at 2250 mg/m2 of capecitabine with 3 out of 3 patients experiencing grade 4 neutropenia plus grade 3 diarrhea and grade 3 oral mucositis in 1 patient). Thus, MTD was defined at 2000 mg/m2 capecitabine. Other observed grade 2 side effects were: 1 patient with neutropenia, 1 with hand-foot syndrome, 2 with mucositis, 1 with cutaneous rash, and 1 with thrombocytopenia. With regard to response rate, we observed 1 complete response (5.5%), 6 partial responses (33%), and 4 disease stabilizations (22%). The median time to progression was 12 weeks and the median survival 41 weeks. The MTD of capecitabine in combination with vinorelbine at 25 mg/m2 dosage on days 1 and 8 of a 3-week schedule is 2000 mg/m2/day for 14 consecutive days. Moreover, this regimen showed interesting activity with 61% overall disease control (complete plus partial response plus disease stabilization) in patients pretreated with anthracyclines and taxanes warranting further investigations in a large, multicenter phase II study.

Amifostine as chemoprotectant in metastatic breast cancer patients treated with doxorubicin.

Amifostine has shown to selectively protect normal tissues against cytotoxic and mutagenic effects of several anti-neoplastic drugs, such as alkylating agents, organoplatinum compounds, anthracyclines, taxanes, and ionising radiation. This cytoprotection is broad-spectrum and selective, without loss of therapeutic efficacy. In this study we have treated 31 patients affected with inoperable or metastatic breast cancer, not previously submitted to chemotherapy for advanced disease, with amifostine 910 mg/m(2) followed by doxorubicin 75 mg/m(2). The overall response rate was 52% with a median response duration of 13 months (range 6-53+) and a median overall survival of 21 months (range 3-59+). With regard to toxicity, 14 patients (45%) experienced transient g4 neutropenia which was febrile only in one case (3%). Grade 3-4 thrombocytopenia was not recorded. Nausea and vomiting occurred in 14% of cycles. Grade 3 mucositis was observed in only 1 patient, whereas 2 patients (6%) developed an asymptomatic drop of left ventricular ejection fraction (LVEF) >10% below basal value. In conclusion, this study suggests that amifostine can reduce doxorubicin related toxicity, thus improving the patients' quality of life and the efficacy/toxicity ratio of this drug.

Current status and future potential role of exemestane in the treatment of early and advanced breast cancer (Review).

Exemestane is a new oral steroidal aromatase inactivator, active in postmenopausal women with hormonal sensitive breast carcinoma. This drug, at a dosage of 25 mg once daily, was shown to suppress in vivo aromatase activity by 97.9%, with a subsequent reduction superior to 85% of circulating oestrogen level. It exhibits definite antitumor activity at a relatively low daily dose, and is highly potent, highly selective, and well-tolerated. Moreover, for postmenopausal women with metastatic breast cancer, exemestane demonstrated a higher activity and lower toxicity profile when compared to megestrol acetate and tamoxifen in second- and first-line therapy, respectively. New data on exemestane are forthcoming both in the adjuvant and neoadjuvant setting, which could improve the management of early breast cancer in the future.

AIDS-related non-Hodgkin's lymphoma: clinico-pathological characteristics and therapeutic strategies (review).

High-grade B-cell non-Hodgkin's lymphoma (NHL), a diagnostic disease for the acquired immunodeficiency syndrome (AIDS), is a late manifestation of HIV infection and is generally related to severe lymphopenia. We reviewed the main clinico-pathological features of this disease and analysed its pathogenetic mechanisms with potential therapeutic implications.

The role of letrozole (Femara(R)) in breast cancer therapy: A clinical review.

Letrozole is a third-generation aromatase inhibitor for use in postmenopausal women with hormonal-sensitive breast cancer. This drug was found to reduce or effectively shrink tumors in a significant number of such patients. It exhibits antitumor activity at a relatively low daily dose, and is highly potent and selective and well tolerated. Results from recent phase III clinical studies have confirmed the efficacy and the key role of this drug in the therapy of advanced breast cancer in postmenopausal women. Moreover, letrozole demonstrated higher activity and lower toxicity compared to tamoxifen in the first-line therapy of postmenopausal women affected with advanced breast cancer. However, it also represents a valid option in second-line therapy after tamoxifen failure. New data on this agent in adjuvant or neoadjuvant treatment also suggest efficacy in the treatment of early breast cancer. This article reviews the clinical data on letrozole in all settings and its future potential in chemoprevention. (c) 2001 Prous Science. All rights reserved.