Evaluation of clinical use and effectiveness of darbepoetin alfa in cancer patients with chemotherapy-induced anemia.

PURPOSE: To investigate the patterns of use of darbepoetin alfa in Spanish centers, and to evaluate its effectiveness in the treatment of chemotherapy-induced anemia under clinical practice conditions. METHODS: This was an observational, retrospective, multicenter study in adult patients with non-myeloid malignancies who initiated chemotherapy and darbepoetin alfa. Data was collected for up to 16 weeks or until treatment discontinuation. RESULTS: A total of 685 patients (72.7% with solid tumors and 27.3% with hematologic malignancies) were included in the study. Median age was 64.7 years (range 18.5-88.9 years), 50.7% were women, 82.4% had ECOG status 0-1 and 80.5% had stage III/IV cancer. At darbepoetin initiation, mean hemoglobin (Hb) was 100 g/L (SD 10), with 11.0% and 23.1% of patients below 90 g/L in solid and hematologic malignancies, respectively. A decrease in transfusion requirements was observed between weeks 5-16 with respect to weeks 0-16 (13.3% [95% CI: 10.7 to 15.9] versus 19.0% [95% CI: 16.0 to 22.0]). Hb levels were significantly increased during the treatment (mean change of 10.4 g/L for solid tumors [p < 0.001], and 16.6 g/L for hematologic malignancies [p < 0.001]). The percentage of patients with baseline Hb level <110 g/L who achieved an Hb level ≥110 g/L during the study was 66.5% (95% CI: 62.5% to 70.5%). Six serious adverse reactions were considered related to darbepoetin alfa (thromboembolic events, 1.0%). CONCLUSIONS: With the limitation of a retrospective design, our results suggest that darbepoetin alfa is a well tolerated treatment that increases hemoglobin levels and reduces the need for transfusion in cancer patients receiving chemotherapy in clinical practice.

Biweekly vinorelbine and tegafur/uracil in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: GEICAM 2000-02 phase II study.

INTRODUCTION: To assess the efficacy and safety profile of biweekly vinorelbine and tegafur/uracil (UFT) as treatment in patients with metastatic breast cancer previously treated with anthracyclines and taxanes. PATIENTS AND METHODS: Patients with histologically confirmed breast cancer, measurable disease, no more than one prior chemotherapy regimen for metastatic disease, an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and adequate bone marrow, renal and liver function were eligible. Patients received vinorelbine (30 mg/m(2) on day 1) and UFT (250 mg/m(2) daily) every two weeks for 12 cycles unless progression or unacceptable toxicity was observed. RESULTS: Thirty-seven patients were included and received 311 cycles of chemotherapy. Efficacy and toxicity analyses were carried out on an intention-to-treat basis. The overall response rate was 35% (95% CI: 20-53). With a median follow-up of 18.6 months (95% CI: 1.0-74.3), the median time to progression was 7.0 months (96% CI: 5.2-8.9) and the median overall survival was 19.4 months (95% CI: 11.1-27.8). The most common severe toxicities were neutropenia (38% of patients) and asthenia (11% of patients). CONCLUSION: The combination of biweekly vinorelbine and UFT in patients with metastatic breast cancer pretreated with anthracyclines and taxanes is a well tolerated and effective regimen. AEMPS Trial Registration No.: 00-0534.

Adjuvant docetaxel for high-risk, node-negative breast cancer.

BACKGROUND: A regimen of docetaxel, doxorubicin, and cyclophosphamide (TAC) is superior to a regimen of fluorouracil, doxorubicin, and cyclophosphamide (FAC) when used as adjuvant therapy in women with node-positive breast cancer. The value of taxanes in the treatment of node-negative disease has not been determined. METHODS: We randomly assigned 1060 women with axillary-node-negative breast cancer and at least one high-risk factor for recurrence (according to the 1998 St. Gallen criteria) to treatment with TAC or FAC every 3 weeks for six cycles after surgery. The primary end point was disease-free survival after at least 5 years of follow-up. Secondary end points included overall survival and toxicity. RESULTS: At a median follow-up of 77 months, the proportion of patients alive and disease-free was higher among the 539 women in the TAC group (87.8%) than among the 521 women in the FAC group (81.8%), representing a 32% reduction in the risk of recurrence with TAC (hazard ratio, 0.68; 95% confidence interval [CI], 0.49 to 0.93; P=0.01 by the log-rank test). This benefit was consistent, regardless of hormone-receptor status, menopausal status, or number of high-risk factors. The difference in survival rates (TAC, 95.2%; FAC, 93.5%) was not significant (hazard ratio, 0.76; 95% CI, 0.45 to 1.26); however, the number of events was small (TAC, 26; FAC, 34). Rates of grade 3 or 4 adverse events were 28.2% with TAC and 17.0% with FAC (P<0.001). Toxicity associated with TAC was diminished when primary prophylaxis with granulocyte colony-stimulating factor was provided. CONCLUSIONS: As compared with adjuvant FAC, adjuvant TAC improved the rate of disease-free survival among women with high-risk, node-negative breast cancer. (Funded by GEICAM and Sanofi-Aventis; ClinicalTrials.gov number, NCT00121992.).

Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer.

UNLABELLED: Treatment with fluororacil, epirubicin, and cyclophosphamide followed by weekly paclitaxel (FEC-P) yielded superior disease-free survival than FEC in the adjuvant breast cancer trial GEICAM 9906. We evaluate molecular subtypes predictive of prognosis and paclitaxel response in this trial. Two molecular subtype classifications based on conventional immunohistochemical and fluorescent in situ hybridization determinations were used: #1: Four groups segregated according to the combination of hormone receptor (HR) and HER2 status; #2: Intrinsic subtype classification (Triple Negative (TN), HER2, Luminal B and Luminal A). RESULTS: Both subtype classifications yielded prognostic and predictive information. HR +/HER2- patients (and Luminal A patients) had a significantly better outcome than the other subgroups of patients. The superiority of FEC-P over FEC was clearly more marked in HR-/HER2- patients (TN patients), particularly in the subset with basal phenotype (TN and either EGFR+ or cytokeratins 5/6+). The Luminal A subtype also achieved a significant benefit with FEC-P. The molecular-defined subgroup of TN was clearly predictive of better response to treatment with FEC-P. Luminal A patients had the best prognosis and also have a better outcome with weekly paclitaxel.

Docetaxel/gemcitabine administered every other week as first-line treatment for metastatic breast cancer: final results of a phase II trial.

BACKGROUND: The purpose of this study was to assess the toxicity and efficacy of the combination of docetaxel and gemcitabine every 2 weeks as first-line therapy in metastatic breast cancer. PATIENTS AND METHODS: We selected patients between the ages of 18 years and 70 years with a Karnofsky performance status of > or = 60 to receive docetaxel 65 mg/m(2) followed by gemcitabine 2500 mg/m(2) on day 1 every 14 days for 10 cycles. Patients could receive more cycles at the discretion of investigator. RESULTS: Of the 52 patients entered, 48 were evaluable for efficacy and toxicity. The overall response rate was 75% (95% confidence interval, 60%-86%), with 8 patients (17%) exhibiting a complete response. The median time to progression was 10.7 months, and the median survival was 32.2 months. The predominant grade 3/4 hematologic toxicity was neutropenia (44% of patients), and the predominant grade 3/4 nonhematologic toxicity was asthenia (15% of patients). Other grade 3/4 toxicities, such as anemia, nausea/vomiting, and diarrhea, were present but infrequent (< or = 10% of patients). The relative dose intensities of both drugs were > 88%. CONCLUSION: The combination of docetaxel/gemcitabine once every 2 weeks is active and well tolerated in patients with untreated advanced breast carcinoma. This chemotherapy regimen might be useful in advanced breast cancer when anthracycline combinations are not preferred, such as cases previously treated with adjuvant anthracycline chemotherapy.

Gemcitabine plus docetaxel administered every other week as first-line treatment of metastatic breast cancer: preliminary results from a phase II trial.

The purpose of this study was to assess the toxicity and efficacy of gemcitabine and docetaxel administered every other week as first-line therapy in metastatic breast cancer. Fifty-one patients with histologically confirmed metastatic breast cancer were enrolled. Patients received docetaxel 65 mg/m(2) followed by gemcitabine 2,500 mg/m(2), both on day 1 of a 14-day cycle, for 10 cycles without granulocyte-colony stimulating factor support. Thirty-five patients were evaluable for toxicity and 32 for efficacy. Median age was 65 years (range, 37 to 72 years), and median performance status was 90 (range, 60 to 100). The number of disease sites was 2 or > or =3 in 39% and 44% of patients, respectively, with visceral involvement in the liver and/or lung in 44% of patients. A total of 45% had received prior adjuvant chemotherapy. So far, 267 cycles have been administered. Twenty-five percent of the docetaxel and gemcitabine doses were reduced or delayed due primarily to neutropenia, giving a median dose intensity of 90% of the planned dose for both drugs. Grade 3/4 toxicities were mainly hematologic, with neutropenia in 46% of patients (two patients experienced neutropenic fever). Other toxicities were asthenia, diarrhea, transaminase elevation, and nausea. Overall response rate was 66% (four complete responses, 17 partial responses), with 22% of patients achieving stable disease. Responses were observed in all disease sites, including lung (60%) as well as liver (37.5%). In conclusion, preliminary evaluation from our phase II study shows that the combination of docetaxel and gemcitabine given every 2 weeks is a tolerable and highly active combination in patients with metastatic breast cancer. These data compare favorably with those obtained with other docetaxel schedules.

Weekly docetaxel as neoadjuvant chemotherapy for stage II and III breast cancer: efficacy and correlation with biological markers in a phase II, multicenter study.

PURPOSE: This is one of the first reports of weekly docetaxel (Taxotere) in the neoadjuvant treatment of stage II and III breast cancer. We evaluated docetaxel's efficacy and safety and analyzed correlations between response and the expression of c-erbB2, ER status, and Ki-67 labeling index. EXPERIMENTAL DESIGN: Patients with previously untreated, stage II and III breast cancer were entered into the study. Docetaxel (40 mg/m(2)) was given i.v. once weekly for the first 6 weeks of an 8-week cycle for 2 cycles. RESULTS: A total of 56 patients were evaluated by intention-to-treat analysis for efficacy and safety. The overall clinical response rate was 68% (complete and partial response, 29 and 39%, respectively). Nine patients (16%) achieved a pathological complete response. There was no correlation between response to docetaxel and the expression of molecular markers, however, the majority of the pathological complete responses were observed in patients with c-erbB2-negative tumors. Nonhematological toxicity was more common than hematological toxicity, with alopecia and asthenia the most frequently reported adverse events (89 and 77% of patients, respectively). Severe hematological toxicity was rare. CONCLUSIONS: Weekly docetaxel appears to be very effective in the neoadjuvant setting. A high pathological response rate was achieved with tolerable toxicity.