[Show abstract][Hide abstract] ABSTRACT: Breast cancer is a burden for western societies, and an increasing one in emerging economies, because of its high incidence and enormous psychological, social, sanitary and economic costs. However, breast cancer is a preventable disease in a significant proportion. Recent developments in the armamentarium of effective drugs for breast cancer prevention (namely exemestane and anastrozole), the new recommendation from the National Institute for Health and Care Excellence to use preventative drugs in women at high risk as well as updated Guidelines from the US Preventive Services Task Force and the American Society of Clinical Oncology should give renewed momentum to the pharmacological prevention of breast cancer. In this article we review recent major developments in the field and examine their ongoing repercussion for breast cancer prevention. As a practical example, the potential impact of preventive measures in Spain is evaluated and a course of practical actions is delineated.
[Show abstract][Hide abstract] ABSTRACT: Febrile neutropenia (FN) is associated with disruption of planned chemotherapy and increased management costs. However, the economic impact of FN in Spanish clinical practice has not been documented hitherto.
A multicenter, retrospective chart review of adults with breast or lung cancer or non-Hodgkin's lymphoma (NHL) who had > or = 1 FN episode during chemotherapy. Resource use, direct costs, and FN effect on planned chemotherapy were assessed.
238 episodes of FN were analyzed in 194 patients. The mean + or - SD length of FN-related hospitalization was 8.7 + or - 6.9 days (median [p(25)-p(75)] = 7 [5-11] days). At least one transfusion was needed in 77 (32.3%) FN episodes, blood tests were done in 233 (97.9%) and blood cultures in 207 (87.0%). Antibiotics were used in all episodes (100%), other drugs in 186 (78.2%) episodes and the granulocyte colony-stimulating factor (G-CSF) in 161 (67.7%) episodes. The distribution of costs per episode of FN were: hospitalization 79%, antibiotics 10%, G-CSF 5%, complementary tests 4%; other drugs 1%, blood transfusions 1%. The estimated mean (95% CI) cost per FN episode was euro3841 (95% CI: euro3476-4206). FN management was costlier in NHL patients euro4514 (95% CI: euro3805-5223) than in breast or lung cancer patients (euro3519 [95% CI: euro2976-4061] and euro3311 [95% CI: euro2817-3805] respectively) (P < 0.05 both comparisons). Planned chemotherapy was disrupted in 139 (58.4%) episodes (dose reductions in 75 [34.9%], dose delays in 60 [28.0%] and withdrawal in 33 [14.7%]).
FN substantially affects healthcare resource use and costs in breast cancer, lung cancer and, NHL. In this study, hospitalization and antibiotics were the main drivers of cost. A limitation of the analysis was that it did not include the indirect costs associated with FN episodes.
Current Medical Research and Opinion 09/2009; 25(10):2533-42. DOI:10.1185/03007990903209563 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Febrile neutropenia (FN), a dose-limiting event for many myelosuppressive chemotherapy (CT) regimens, often causes subsequent CT dose delays (DD) and reductions (DR), lengthens hospital stay and increases monitoring, diagnostic and treatment costs. No studies are known to date on economic costs of FN in common clinical practice in Spain. Methods: This is a multicentre, retrospective, observational chart review of adult patients with breast cancer, lung cancer or non-Hodgkin’s lymphoma (NHL) who suffered from at least one FN episode related to cytotoxic CT from 16 Spanish hospitals. Resource use and subsequent costs including days of hospitalization, number of RBC transfusions, number and type of complementary tests, use of colony-stimulating factors (CSF), antibiotics and other drugs to manage FN were assessed. Potential impact of FN on planned CT dose and/or schedule was also analysed. P-value was obtained by one-way ANOVA using the Bonferroni correction. Results: A total of 194 medical charts including 238 documented FN episodes were reviewed. Women, 59.8%; age > 60 yrs, 49.5%; breast cancer, 43% (83% treated with taxane or anthracycline-based CT); lung cancer, 22% (95.5% treated with platinum-based CT); NHL, 35% (58.2% treated with CHOP-like CT). Hospitalization due to FN lasted a median of 7 days. During the episode, 32.3% of pts needed 1 or more RBC transfusions, 97.9% required a blood test and 87% a blood culture. CSFs were used in 67.6% of pts. All pts were treated with antibiotics and 78.2% with other drugs. 58.4% of FN episodes had an impact on planned CT dose and/or schedule: DR was observed in 34.9% of cases, DD in 28% and CT withdrawal in 14.7%. Conclusions: Main drivers of cost of FN are hospitalization and antibiotic treatment. FN is more costly in NHL pts than breast or lung pts (statistically significant in lung pts). FN episodes have a relevant impact on planned CT dose and/or schedule. In each row statistically significant differences ( p<0.05) were obtained between values with the same letter.
[Show abstract][Hide abstract] ABSTRACT: 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.
Four-hundred and eighty-five patients with node-positive operable disease were randomized to receive tamoxifen (20 mg/day) concomitantly (CON) or sequentially (SEQ) to EC chemotherapy (epirubicin 75 mg/m(2) + cyclophosphamide 600 mg/m(2) on day 1, every 21 days for four cycles).
In the 474 fully evaluable patients there were 96 events; eight being second neoplasms and 88 being related to the breast cancer. Of these, 48 of 88 occurred in the CON arm and 40 of 88 in the SEQ arm. The Kaplan-Meier estimation of disease-free survival (DFS) at 5 years was 70% in the CON and 75% in the SEQ group (log-rank test, P = 0.43). Adjusted hazard ratio for treatment was 1.11 (95% confidence interval 0.71-1.73; P = 0.64).
This study fails to show an advantage of one treatment arm over the other, but a trend, albeit non-significant, appears to favor the sequential addition of tamoxifen to epirubicin + cyclophosphamide and, as such, warrants further investigation.
Annals of Oncology 02/2004; 15(1):79-87. DOI:10.1093/annonc/mdh016 · 7.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this multicentre phase II study, the efficacy and safety profile of the combination of docetaxel and epirubicin as first-line chemotherapy for metastatic breast cancer (MBC) were evaluated.
Epirubicin (75 mg/m(2)) and docetaxel (75 mg/m(2)) were given intravenously once every 3 weeks for six cycles to 133 patients with MBC.
The overall clinical response rate was 67% (complete and partial responses were 23% and 44%, respectively). The median time to progression was 10.8 months (95% CI 9.7-12.6) and the median overall survival was 19.5 months. Granulocyte colony-stimulating factor support was administered to 32% of patients and in 22% of cycles. Grade 3/4 neutropenia occurred in 35% of patients and febrile neutropenia in 19%. The most frequent grade 3/4 non-haematological toxicities (as percent of patients) were asthenia (6%), vomiting (5%) and nausea (5%). No patients developed congestive heart failure.
The combination of docetaxel and epirubicin was highly active as first-line treatment for MBC and showed a manageable toxicity profile.
Cancer Chemotherapy and Pharmacology 02/2004; 53(1):75-81. DOI:10.1007/s00280-003-0690-0 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study compared the efficacy and safety of 5-fluorouracil (5-FU) monotherapy to that of 5-FU combined with natural human interferon-beta (IFN-beta) in patients with unresectable, advanced colorectal carcinoma. Forty-nine chemotherapy-naive patients were randomized to 5-FU alone or to the combination. All patients received 750 mg m(-2) day(-1) 5-FU for 5 days by continuous intravenous (i.v.) infusion, followed after day 15 by a weekly i.v. bolus of 750 mg m(-2). IFN-beta was injected intramuscularly three times weekly at 9 M IU. Treatment continued for 52 weeks, or until disease progression or intolerable toxicity. Clinical endpoints were tumor response, time to progression, survival and toxicity. The addition of IFN-3 to 5-FU significantly improved response rate (33.3% vs 4.5% for evaluable patients; P = 0.021), time to progression (median 7.2 vs 4.2 months; P = 0.0435), and survival time (median 15.9 vs 7.2 months; P = 0.038) without significantly increasing toxicity compared to 5-FU alone. Cumulative 5-FU dose was higher with combined therapy (P < 0.001): more patients receiving monotherapy discontinued treatment because of disease progression. Fever was more frequent with combined therapy (P = 0.008); there were no other differences in toxicity. The only grade IV toxicity observed was neutropenia (two patients per group). A randomized phase III trial has been initiated to confirm the synergy between 5-FU and IFN-beta.
British Journal of Cancer 05/1999; 80(5-6):786-91. DOI:10.1038/sj.bjc.6690422 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Forty-six patients were included in a phase II study to evaluate the response rate and toxicity of a combination of ifosfamide and vinorelbine in metastatic breast cancer patients previously treated with one or more regimens of chemotherapy. Treatment consisted of ifosfamide 1.6 g/m(2) IV days 1-3 (with mesna) and vinorelbine 25 mg/m(2) IV days 1 and 8, every 3 weeks up to 6 cycles. The median age was 55 years (range 40-76), the World Health Organization (WHO) performance status was 0-1 in 93% of the patients and 2 in the remaining 7%. In all, 43% had received two or more previous lines of chemotherapy, and 91% had been treated with anthracyclines. Forty-four patients were evaluable for response, and all patients for toxicity. The overall response rate was 36.4% [95% confidence interval (CI) 22.4-52.2]. Stabilization was observed in 20.4% and progression in 43.2%. The median time to progression was 25 weeks (95% CI 14-36). Median relative dose intensity (=actual received dose intensity/planned dose intensity) was 0.99 for ifosfamide and 0. 80 for vinorelbine. The main toxicity was hematological, with 63% of the patients experiencing grade 3-4 neutropenia. With a moderate toxicity, this is an active regimen that may be taken into consideration in pretreated metastatic breast cancer patients when further chemotherapy is indicated.
Cancer Chemotherapy and Pharmacology 02/1999; 44 Suppl(7):S5-8. DOI:10.1007/s002800051108 · 2.77 Impact Factor