National expert consensus on home-administered oncologic therapies in Spain.

The diagnosis and treatment of cancer impose a significant emotional and psychological burden on patients, families, and caregivers. Patients undergo several interventions in a hospital setting, and the increasing number of patients requiring extended care and follow-up is driving the demand for additional clinical resources to address their needs. Hospital at Home (HaH) teams have introduced home-administered oncologic therapies that represent a new model of patient-centered cancer care. This approach can be integrated with traditional models and offers benefits to both patients and healthcare professionals (HCPs). Home-administered treatment programs have been successfully piloted globally, demonstrated as a preferred option for most patients and a safe alternative that could reduce costs and hospital burden. The document aims to establish the minimum recommendations for the home administration of oncologic therapies (ODAH) based on a national expert agreement. The expert panel comprised seven leading members from diverse Spanish societies and three working areas: clinical and healthcare issues, logistical and administrative issues, and economic, social, and legal issues. The recommendations outlined in this article were obtained after a comprehensive literature review and thorough discussions. This document may serve as a basis for the future development of home-administered oncologic therapy programs in Spain. .

Observational study of HR+/HER2- metastatic breast cancer patients treated with abemaciclib in Spain in the Named Patient Use Program (AbemusS).

INTRODUCTION/OBJECTIVES: To describe abemaciclib use in patients with hormone receptor-positive, human epidermal growth factor receptor-negative (HR+/HER2-) metastatic breast cancer (mBC) who participated in the Named Patient Use program (NPU) in Spain. MATERIAL AND METHODS: This retrospective study was based on medical record review of patients across 20 centers during 2018/2019. Patients were followed up until death, enrolment in a clinical trial, loss of follow-up or study end. Clinical and demographic characteristics, treatment patterns and abemaciclib effectiveness were analyzed; time-to-event and median times were estimated using the Kaplan-Meier (KM) method. RESULTS: The study included 69 female patients with mBC (mean age 60.4 ± 12.4 years), 86% of whom had an initial diagnosis of early BC and 20% had an ECOG ≥ 2. Median follow-up was 23 months (range 16-28). Metastases were frequently observed in bone (79%) and visceral tissue (65%), with 47% having metastases in > 2 sites. Median number of treatment lines before abemaciclib was 6 (range 1-10). Abemaciclib monotherapy was received by 72% of patients and combination therapy with endocrine therapy by 28% of patients; 54% of patients required dose adjustments, with a median time to first adjustment of 1.8 months. Abemaciclib was discontinued in 86% of patients after a median of 7.7 months (13.2 months for combination therapy and 7.0 months for monotherapy) mainly due to disease progression (69%). CONCLUSION: These results suggest that abemaciclib is effective, as monotherapy and in combination, for patients with heavily pretreated mBC, consistent with clinical trial results.

The role of immunotherapy in non-clear cell renal cell carcinoma.

The category of non-clear cell renal cell carcinoma (nccRCC) includes several clinically, histologically, and molecularly diverse entities. Traditionally, they comprise type 1 and type 2 papillary, chromophobe, unclassified, and other histologies (medullary, collecting duct carcinoma, and translocation-associated). Molecular knowledge has allowed the identification of some other specific subtypes, such as fumarate hydratase-deficient renal cell carcinoma (RCC) or succinate dehydrogenase-associated RCC. In addition, it has recognized some alterations with a possible predictive role, e.g., MET proto-oncogene receptor tyrosine kinase (MET) alterations in papillary tumors. Standard therapies for the management of advanced clear cell RCC (ccRCC), i.e., vascular endothelial growth factor receptor (VEGFR) pathway inhibitors and mammalian target of rapamycin inhibitors, have shown poorer results in nccRCC patients. Therefore, there is a need to improve the efficacy of the treatment for advanced nccRCC. Immunotherapy, especially immune checkpoint inhibitors (ICIs) targeting programmed death 1/programmed death ligand 1 and cytotoxic T-lymphocyte associated protein 4 (CTLA-4), has demonstrated a significant survival benefit in several malignant neoplasias, including ccRCC, with a proportion of patients achieving long survival. The combinations of ICI or ICI + VEGFR tyrosine kinase inhibitors (TKIs) are the standard of care in advanced ccRCC. Unfortunately, major pivotal trials did not include specific nccRCC populations. In recent years, several studies have retrospectively or prospectively evaluated ICIs alone or in combination with another ICI or with TKIs in nccRCC patients. In this article, we review data from available trials in order to elucidate clinical and molecular profiles that could benefit from immunotherapy approaches.

Palbociclib and ribociclib in breast cancer: consensus workshop on the management of concomitant medication.

Drug-drug interactions are of significant concern in clinical practice in oncology, particularly in patients receiving Cyclin-dependent kinase (CDK) 4/6 inhibitors, which are typically exposed to long-term regimens. This article presents the highlights from the 'First Workshop on Pharmacology and Management of CDK4/6 Inhibitors: Consensus about Concomitant Medications'. The article is structured into two modules. The educational module includes background information regarding drug metabolism, corrected QT (QTc) interval abnormalities, management of psychotropic drugs and a comprehensive review of selected adverse effects of palbociclib and ribociclib. The collaborative module presents the conclusions of the five working groups, each of which comprised five experts from different fields. From these conclusions positive lists of drugs for treating common comorbid conditions that can be safely administered concomitantly with palbociclib and/or ribociclib were developed.

Frequency of breast cancer with hereditary risk features in Spain: Analysis from GEICAM "El Álamo III" retrospective study.

PURPOSE: To determine the frequency of breast cancer (BC) patients with hereditary risk features in a wide retrospective cohort of patients in Spain. METHODS: a retrospective analysis was conducted from 10,638 BC patients diagnosed between 1998 and 2001 in the GEICAM registry "El Álamo III", dividing them into four groups according to modified ESMO and SEOM hereditary cancer risk criteria: Sporadic breast cancer group (R0); Individual risk group (IR); Familial risk group (FR); Individual and familial risk group (IFR) with both individual and familial risk criteria. RESULTS: 7,641 patients were evaluable. Of them, 2,252 patients (29.5%) had at least one hereditary risk criteria, being subclassified in: FR 1.105 (14.5%), IR 970 (12.7%), IFR 177 (2.3%). There was a higher frequency of newly diagnosed metastatic patients in the IR group (5.1% vs 3.2%, p = 0.02). In contrast, in RO were lower proportion of big tumors (> T2) (43.8% vs 47.4%, p = 0.023), nodal involvement (43.4% vs 48.1%, p = 0.004) and lower histological grades (20.9% G3 for the R0 vs 29.8%) when compared to patients with any risk criteria. CONCLUSIONS: Almost three out of ten BC patients have at least one hereditary risk cancer feature that would warrant further genetic counseling. Patients with hereditary cancer risk seems to be diagnosed with worse prognosis factors.

Nab-Paclitaxel in Metastatic Breast Cancer: Defining the Best Patient Profile.

Around 40% of patients with breast cancer will present with a recurrence of the disease. Chemotherapy is recommended for patients with recurrent hormone-independent or hormone-refractory breast cancer and almost all patients with metastatic breast cancer (MBC) receive chemotherapy during their medical history. Nanoparticle albuminbound (nab)-paclitaxel is a solvent-free, 130-nanometer particle formulation of paclitaxel. Nab-paclitaxel can be administered to all patients for whom the treatment choice is a taxane. In this review, 6 patient profiles for which nabpaclitaxel may be particularly useful are described and analyzed: (i) as first-line treatment of MBC, (ii) as second-line treatment of MBC after oral chemotherapy, (iii) after a standard taxane, (iv) as third-line treatment after a standard taxane and oral chemotherapy, (v) for patients with HER2-positive MBC and (vi) for patients with intolerance to standard taxanes. Nab-paclitaxel is a rational treatment choice for patients with MBC in different settings, as well as for those with prior exposure to a standard taxane.

Genomic profile of breast cancer: cost-effectiveness analysis from the Spanish National Healthcare System perspective.

BACKGROUND: Cost-effectiveness analysis of MammaPrint(®) (70-gene signature) in the diagnosis of early breast cancer as a prognosis assay to study the risk of tumor recurrence to administer adjuvant chemotherapy. METHODS: Markov model assuming a cohort of 60-year-old women with breast cancer. Treatment costs and effects were assessed by comparing the 5-year, 10-year and lifetime risk of recurrence using Adjuvant! Online(®) (online algorithm), 70-gene signature or Oncotype DX(®) (21-gene assay). RESULTS: 70-gene signature showed a life expectancy of 23.55 years at lifetime. Life expectancy was lower for 21-gene assay and online algorithm, with associated quality-adjusted life year gains up to 0.23 and 0.75, respectively, with 70-gene signature. At year 5, the mean cost of 21-gene assay, 70-gene signature and online algorithm was €7100, €6380 and €4580, respectively. 70-gene signature was dominant versus 21-gene assay at any time horizon and would be cost-effective from year 7 versus online algorithm (lifetime: €1457 per quality-adjusted life years gained). CONCLUSIONS: 70-gene signature was a dominant strategy over 21-gene assay and was highly cost-effective versus online algorithm.

Bone turnover markers as predictive indicators of outcome in patients with breast cancer and bone metastases treated with bisphosphonates: results from a 2-year multicentre observational study (ZOMAR study).

BACKGROUND: We evaluated the evolution and predictive value of bone turnover markers (BTMs) and circulating tumor cells (CTCs) with respect to mortality, disease progression (DP) and skeletal-related events (SREs), in patients with bone metastatic breast cancer (BmBCa). The correlation between BTMs and CTCs was also studied. METHODS: In a 2-year observational, multicenter study, the levels of three BTMs (N- and C-terminal telopeptides of collagen I [NTX and αα-CTX], and bone-specific alkaline phosphatase [BSAP]) and CTCs were analyzed every three months. Patients received zoledronic acid (4mg every 28days) from the baseline visit. RESULTS: 234 patients were analyzed. The levels of the BTMs were increased at baseline and significantly decreased after 3months (P<0.05). In the Cox regression univariate analyses significant hazard ratios (HRs) for death were found for pathological BSAP values at baseline (5.03 [95% CI: 1.214-20.839; P=0.0259]) and at 3months (3.41 [95% CI: 1.367-8.498; P=0.0085]). HRs >2 were found for increased baseline and 3-month levels of NTX and CTC (P<0.05). Only increased baseline BSAP levels were associated with DP (HR=2.25 [95% CI: 1.391-3.626; P=0.0009]). No biomarker was associated with SREs. In the multivariate analysis, pathologic levels at 3months of NTX and BSAP were significantly associated with mortality (HRs=3.59 [95% CI: 1.375-9.382; P=0.0091] and 3.25 [95% CI: 1.293-8.189; P=0.0120], respectively). CTC and BSAP were correlated during all study timepoints (P<0.05). CONCLUSIONS: Baseline levels of NTX, BSAP and CTCs, and changes after treatment initiation with bisphosphonates, may be useful for the prognostic assessment of patients with BmBCa. BSAP showed the strongest prognostic value.

Treatment innovations for metastatic breast cancer: nanoparticle albumin-bound (NAB) technology targeted to tumors.

In spite of recent advances in the treatment of metastatic breast cancer, this disease remains essentially incurable. Anthracyclines and taxanes have been widely demonstrated to be the most active cytotoxic drugs for the treatment of breast cancer. Paclitaxel and docetaxel are both hydrophobic drugs that need to be administered with detergent-like substances as solvents. In contrast, nanoparticle albumin-bound (nab) paclitaxel uses the natural characteristics of albumin to reversibly bind paclitaxel, transport it across endothelial cells and concentrate the active ingredient within the tumor. Several trials have demonstrated that nab-paclitaxel results in superior efficacy, with more complete responses, prolonged time to recurrence and survival, than paclitaxel and docetaxel in MBC. As second-line treatment, the novel formulation has almost doubled overall response rate, increased time to progression and overall survival in comparison with paclitaxel. Due to these results, to date nab-paclitaxel stands out as a promising treatment of metastatic breast cancer.

Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis.

INTRODUCTION: Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification. METHODS: We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003-02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype. RESULTS: Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype. CONCLUSIONS: Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes.

Cost-utility analysis of nanoparticle albumin-bound paclitaxel versus paclitaxel in monotherapy in pretreated metastatic breast cancer in Spain.

AIM: The COSTABRAX study evaluated the cost-effectiveness of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) versus polyethylated castor oil-based standard paclitaxel (sb-paclitaxel) in the treatment of patients with previously treated metastatic breast cancer in Spain. MATERIALS & METHODS: Efficacy data were obtained from the CA012 trial (nab-paclitaxel administered every 3 weeks [q3w] and sb-paclitaxel q3w) and indirect comparison (sb-paclitaxel administered weekly), and were modeled to a time horizon of 5 years using a Markov model. The analysis was performed from the National Health Service perspective. Use of resources and key assumptions of the model were validated by a panel of 22 local oncologists. RESULTS: Compared with sb-paclitaxel q3w, nab-paclitaxel q3w was cost effective, with a cost per life year gained of €11,088 and a cost per quality-adjusted life year of €17,808. Compared with sb-paclitaxel administered weekly, it showed savings of €711 per patient. CONCLUSION: The COSTABRAX study showed that nab-paclitaxel q3w is a cost-effective alternative compared with sb-paclitaxel q3w and a cost-saving alternative to sb-paclitaxel administered weekly in Spain.

PAM50 breast cancer subtyping by RT-qPCR and concordance with standard clinical molecular markers.

BACKGROUND: Many methodologies have been used in research to identify the "intrinsic" subtypes of breast cancer commonly known as Luminal A, Luminal B, HER2-Enriched (HER2-E) and Basal-like. The PAM50 gene set is often used for gene expression-based subtyping; however, surrogate subtyping using panels of immunohistochemical (IHC) markers are still widely used clinically. Discrepancies between these methods may lead to different treatment decisions. METHODS: We used the PAM50 RT-qPCR assay to expression profile 814 tumors from the GEICAM/9906 phase III clinical trial that enrolled women with locally advanced primary invasive breast cancer. All samples were scored at a single site by IHC for estrogen receptor (ER), progesterone receptor (PR), and Her2/neu (HER2) protein expression. Equivocal HER2 cases were confirmed by chromogenic in situ hybridization (CISH). Single gene scores by IHC/CISH were compared with RT-qPCR continuous gene expression values and "intrinsic" subtype assignment by the PAM50. High, medium, and low expression for ESR1, PGR, ERBB2, and proliferation were selected using quartile cut-points from the continuous RT-qPCR data across the PAM50 subtype assignments. RESULTS: ESR1, PGR, and ERBB2 gene expression had high agreement with established binary IHC cut-points (area under the curve (AUC) ≥ 0.9). Estrogen receptor positivity by IHC was strongly associated with Luminal (A and B) subtypes (92%), but only 75% of ER negative tumors were classified into the HER2-E and Basal-like subtypes. Luminal A tumors more frequently expressed PR than Luminal B (94% vs 74%) and Luminal A tumors were less likely to have high proliferation (11% vs 77%). Seventy-seven percent (30/39) of ER-/HER2+ tumors by IHC were classified as the HER2-E subtype. Triple negative tumors were mainly comprised of Basal-like (57%) and HER2-E (30%) subtypes. Single gene scoring for ESR1, PGR, and ERBB2 was more prognostic than the corresponding IHC markers as shown in a multivariate analysis. CONCLUSIONS: The standard immunohistochemical panel for breast cancer (ER, PR, and HER2) does not adequately identify the PAM50 gene expression subtypes. Although there is high agreement between biomarker scoring by protein immunohistochemistry and gene expression, the gene expression determinations for ESR1 and ERBB2 status was more prognostic.

Cost-effectiveness analyses of docetaxel versus paclitaxel once weekly in patients with metastatic breast cancer in progression following anthracycline chemotherapy, in Spain.

OBJECTIVES: Our aim was to evaluate the cost-effectiveness of docetaxel versus weekly paclitaxel regimen in patients with metastatic breast cancer previously treated with anthracycline from the Spanish National Health Service (NHS) perspective. METHODS: A Markov model with a 21-day cycle duration was developed to estimate total treatment-related costs and clinical benefits over 5 years of docetaxel (100 mg/m²) and weekly paclitaxel (80 mg/m²). Patient data were obtained from the Randomized Phase III Study of Docetaxel Compared with Paclitaxel in Metastatic Breast Cancer (TAX- 311) and Anglo-Celtic IV trials. Utilities were obtained from literature, and unitary costs (€2009) from a Spanish health-cost database and the Catalogue of Medicines. Cost and benefits [life-years gained (LYG) and quality-adjusted life years (QALY)] were discounted at 3%. Sensitivity analyses were performed. RESULTS: Docetaxel yields higher health benefits (1.83 LYG; 1.08 QALY) than paclitaxel (1.46 LYG; 0.84 QALY). Global costs (treatment, concomitant medication, adverse events management, progression, best supportive care, and end of life phase) per patient were €20,052 and €9,982 with docetaxel and paclitaxel, respectively. Incremental cost-effectiveness ratio (ICER) of docetaxel versus paclitaxel was €190/LYG and €295/QALY. Based on a €30,000/QALY threshold, docetaxel has 99% probability of being cost-effective. ICER was mostly sensitive to hazard ratio (HR) (when varied from 1.46 to 1.09; €3,517/ QALY), discount over the ex-lab price of Taxol® (75%; €6,396/QALY) and granulocyte colony-stimulating factor (G-CSF) prophylactic treatment (when administered in 60% of cycles instead of 100%; cost saving). Variations in other inputs, such as time horizon (3-10 years), discount rate (0-5%), or adverse event cost (± 25%) were shown not to have relevant influence on the results. CONCLUSION: Compared to weekly paclitaxel, docetaxel therapy is cost effective for treating metastatic breast cancer patients.

Current perspectives of treatment of ductal carcinoma in situ.

DCIS is a genetically diverse group of diseases with different prognosis. The similarities between DCIS and ductal infiltrating carcinoma (DIC) suggest that the key step in tumorigenesis is the transformation from high grade ductal hyperplasia to DCIS. The prognostic factors of DCIS include anatomo-pathologic factors, age and molecular factors. The key questions for DCIS management include: which patients are more likely to present an invasive failure; in which an excision is sufficient and who can be spared from radiation therapy. The role of post operative radiation therapy to reduce by 50-60% ipsilateral invasive and non-invasive local failure has been established in four randomized clinical trials. The question whether radiation therapy can be avoided in some patients remains controversial. Treatment with tamoxifen should be recommended to patients with estrogen receptor positive tumors who have been treated with conservative surgery. However, data from randomized trials suggest that addition of tamoxifen to locoregional treatment decreases the recurrence rate of invasive cancer as well as contralateral tumors. Sentinel lymph node biopsy is recommended for patients with clinically palpable, large DCIS in which the risk of microinvasion is high as well as in extensive DCIS requiring mastectomy. Mammography continues to be the best method to detect DCIS. Newer digital mammography improves the detection of microcalcifications. Current ultrasound can detect associated invasive cancer. MRI is also useful in DCIS. Combined with mammography, MRI increases the diagnoses of DCIS. Current trend includes the use of radiology guided-vacuum assisted-large bore needles that allow obtaining larger amounts of tissue, improving diagnostic yield.

Supportive care for patients with early breast cancer.

Breast cancer treatment currently requires the joint efforts of a multidisciplinary team to effectively combine chemotherapy, hormone therapy, biological agents, surgery and radiation therapy when needed. To develop such a treatment plan, it is important to know the benefits as well as the potential toxic effects of each therapy. Thus, many patients with early breast cancer complain of collateral adverse events such as fatigue, nausea, vomiting, loss of libido, hot flashes, night sweats or neuropathy due to the complex therapies they are receiving. To date, the treatment of such symptoms is an important issue that greatly affects the quality of life of these patients. In this review, we report the content of a multi-expert meeting where the incidence of and medical approach to some of the most common adverse events encountered during the treatment of patients with early breast cancer were analysed.

Evaluation of international treatment guidelines and prognostic tests for the treatment of early breast cancer.

The clinical decision to treat early-stage breast cancer with adjuvant chemotherapy is sometimes a difficult one because 70-80% of patients who receive chemotherapy would probably have survived without it. To help clinicians in this decision-making process, different tools or 'decision aids' have been developed for the treatment of early breast cancer over the years. Some of these tools include clinical treatment guidelines and computer-based programs as well as different prognostic and/or predictive tests such as those based on gene expression profiles or the presence minimum invasive disease. All of these tools try to individualize as much as possible the estimation of the risk of breast cancer relapse and death and to facilitate the clinical decision about giving additional treatment, and ultimately the most appropriate treatment to be given. Thus, it is important for clinicians to be aware of not only the existence of these tools or 'decision aids', but also to know how they have been developed, how frequently there are revised and if they have been validated. In order to address all these concerns, we have carried out a critical review of the most important prognostic tests and clinical guidelines for the treatment of early breast cancer. Information regarding their development process as well as frequency of revision, validations that have been performed and main limitations of each tool were gathered and critically analyzed.

Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by Paclitaxel for early breast cancer.

BACKGROUND: Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. METHODS: After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. RESULTS: Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. CONCLUSIONS: Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.

The use of taxanes in the neoadjuvant treatment of breast cancer: a review of randomized phase II/III trials.

This review examines all randomized studies that evaluated the role of taxanes in the neoadjuvant treatment of breast cancer and have reported results in terms of efficacy and tolerance. The primary objective of this review was to evaluate whether, at this point in time, there is sufficient evidence to support the routine use of taxanes in the neoadjuvant treatment of breast cancer. Other objectives were to determine the optimal schedule in which to administer taxanes and anthracyclines and whether the addition of other antitumor drugs improves the efficacy of these anthracycline/taxane-based schedules. A literature search revealed 9 major randomized clinical trials published to date. To facilitate analysis, they were classified according to their protocol design. Five trials evaluated the effect of the addition of a taxane to an anthracycline-based schedule, either concomitantly or sequentially. The remaining 4 trials contained taxanes in both treatment arms in an attempt to optimize the administration schedule of anthracyclines and taxanes, or to improve efficacy by adding a further antitumor drug. This type of analysis has provided the opportunity to draw some conclusions regarding the optimal use of taxanes.

Evidence-based use of taxanes in the adjuvant setting of breast cancer. A review of randomized phase III trials.

Six major randomized clinical trials evaluating the role of taxanes in the adjuvant setting of breast cancer have demonstrated significant improvements in terms of efficacy in favour of the taxane treatment arm. In all cases, different anthracycline-based regimens were used as the control arm. Nevertheless, many clinicians are still not sufficiently convinced to incorporate the routine use of taxanes in the adjuvant treatment of breast cancer. There are two main objections, first the possible lack of effectiveness of chemotherapy in hormone-receptor positive tumors and second, some of the anthracycline-based control arms used in these trials were not the optimal ones. In this review, we have searched and analyzed all randomized studies that evaluated the role of taxanes in the adjuvant setting of breast cancer patients and have reported results in terms of efficacy or tolerance. The suitability of the control arm, the prospective definition of patient's subgroups and the statistical methodology were taking into account. The objective of this review was to analyze if, at this point in time, there is sufficient evidence to support the routine use of taxanes in the adjuvant setting of breast cancer, and if it is valid for all subgroups including hormone-receptor and Her2/neu positive breast cancer patients. Other objectives of this review were to define the optimal regimen for administration of taxanes, how the tolerability of taxanes may be improved and also, to investigate any potential differences in efficacy or tolerability between docetaxel and paclitaxel.