RESUMEN
BACKGROUND: Disease progression in patients with HER2-positive breast cancer receiving trastuzumab might be associated with activation of the PI3K/Akt/mTOR intracellular signalling pathway. We aimed to assess whether the addition of the mTOR inhibitor everolimus to trastuzumab might restore sensitivity to trastuzumab. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited women with HER2-positive, trastuzumab-resistant, advanced breast carcinoma who had previously received taxane therapy. Eligible patients were randomly assigned (1:1) using a central patient screening and randomisation system to daily everolimus (5 mg/day) plus weekly trastuzumab (2 mg/kg) and vinorelbine (25 mg/m(2)) or to placebo plus trastuzumab plus vinorelbine, in 3-week cycles, stratified by previous lapatinib use. The primary endpoint was progression-free survival (PFS) by local assessment in the intention-to-treat population. We report the final analysis for PFS; overall survival follow-up is still in progress. This trial is registered with ClinicalTrials.gov, number NCT01007942. FINDINGS: Between Oct 26, 2009, and May 23, 2012, 569 patients were randomly assigned to everolimus (n=284) or placebo (n=285). Median follow-up at the time of analysis was 20.2 months (IQR 15.0-27.1). Median PFS was 7.00 months (95% CI 6.74-8.18) with everolimus and 5.78 months (5.49-6.90) with placebo (hazard ratio 0.78 [95% CI 0.65-0.95]; p=0.0067). The most common grade 3-4 adverse events were neutropenia (204 [73%] of 280 patients in the everolimus group vs 175 [62%] of 282 patients in the placebo group), leucopenia (106 [38%] vs 82 [29%]), anaemia (53 [19%] vs 17 [6%]), febrile neutropenia (44 [16%] vs ten [4%]), stomatitis (37 [13%] vs four [1%]), and fatigue (34 [12%] vs 11 [4%]). Serious adverse events were reported in 117 (42%) patients in the everolimus group and 55 (20%) in the placebo group; two on-treatment deaths due to adverse events occurred in each group. INTERPRETATION: The addition of everolimus to trastuzumab plus vinorelbine significantly prolongs PFS in patients with trastuzumab-resistant and taxane-pretreated, HER2-positive, advanced breast cancer. The clinical benefit should be considered in the context of the adverse event profile in this population.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Sirolimus/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Supervivencia sin Enfermedad , Método Doble Ciego , Everolimus , Femenino , Genes erbB-2 , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Sirolimus/uso terapéutico , Trastuzumab , Resultado del TratamientoRESUMEN
BACKGROUND: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer. We argue that the two anti-HER2 agents given together would be better than single-agent therapy. METHODS: In this parallel groups, randomised, open-label, phase 3 study undertaken between Jan 5, 2008, and May 27, 2010, women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were randomly assigned to oral lapatinib (1500 mg), intravenous trastuzumab (loading dose 4 mg/kg [DOSAGE ERROR CORRECTED], subsequent doses 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab. Treatment allocation was by stratified, permuted blocks randomisation, with four stratification factors. Anti-HER2 therapy alone was given for the first 6 weeks; weekly paclitaxel (80 mg/m(2)) was then added to the regimen for a further 12 weeks, before definitive surgery was undertaken. After surgery, patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks. The primary endpoint was the rate of pathological complete response (pCR), analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00553358. FINDINGS: 154 patients received lapatinib, 149 trastuzumab, and 152 the combination. pCR rate was significantly higher in the group given lapatinib and trastuzumab (78 of 152 patients [51·3%; 95% CI 43·1-59·5]) than in the group given trastuzumab alone (44 of 149 patients [29·5%; 22·4-37·5]; difference 21·1%, 9·1-34·2, p=0·0001). We recorded no significant difference in pCR between the lapatinib (38 of 154 patients [24·7%, 18·1-32·3]) and the trastuzumab (difference -4·8%, -17·6 to 8·2, p=0·34) groups. No major cardiac dysfunctions occurred. Frequency of grade 3 diarrhoea was higher with lapatinib (36 patients [23·4%]) and lapatinib plus trastuzumab (32 [21·1%]) than with trastuzumab (three [2·0%]). Similarly, grade 3 liver-enzyme alterations were more frequent with lapatinib (27 [17·5%]) and lapatinib plus trastuzumab (15 [9·9%]) than with trastuzumab (11 [7·4%]). INTERPRETATION: Dual inhibition of HER2 might be a valid approach to treatment of HER2-positive breast cancer in the neoadjuvant setting. FUNDING: GlaxoSmithKline.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/antagonistas & inhibidores , Neoplasias de la Mama/química , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/antagonistas & inhibidores , Administración Oral , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Diarrea/inducido químicamente , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Lapatinib , Hígado/efectos de los fármacos , Hígado/metabolismo , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Receptor ErbB-2/análisis , Trastuzumab , Resultado del TratamientoRESUMEN
BACKGROUND: Dual anti-HER2-targeted therapy in breast cancer (BC) significantly increased the rate of pathological complete response (pCR) compared to single blockade when added to chemotherapy. However, limited data exist on the long-term impact on survival of the additional increase in pCR. METHODS: Neoadjuvant lapatinib and/or trastuzumab treatment optimisation (NCT00553358) is an international, randomised, open-label, phase III study investigating the addition of lapatinib to chemotherapy plus trastuzumab in HER2-positive early BC. Ten-year event-free survival (EFS), overall survival (OS) and safety were assessed on intention-to-treat population. The association between pCR and EFS or OS was investigated in landmark population. RESULTS: A total of 455 patients were randomised to receive lapatinib (154), trastuzumab (149) or the combination (152). Ten-year EFS estimates were 63% (95% confidence interval [CI], 54%-71%) in the lapatinib group, 64% (95% CI, 55%-72%) in the trastuzumab group and 67% (95% CI, 58%-74%) in the combination group. Ten-year OS rates were 76% (95% CI, 67%-83%), 75% (95% CI, 66%-82%) and 80% (95% CI, 73%-86%) in the lapatinib, trastuzumab and combination groups, respectively. Women who achieved a pCR had improved EFS (hazard ratio 0.48, 95% CI, 0.31-0.73) and OS (hazard ratio 0.37, 95% CI, 0.20-0.63) compared with those who did not. The numerical difference in survival according to pCR status was greater in women treated with the combination and those with hormone-receptor-negative tumours. There were no new or long-term safety concerns. CONCLUSIONS: Patients with HER2-positive BC showed a durable survival benefit of neoadjuvant anti-HER2, irrespective of treatment arm. Patients who achieve pCR have significantly better outcomes than patients without pCR.
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Neoplasias de la Mama , Humanos , Femenino , Masculino , Neoplasias de la Mama/patología , Lapatinib/uso terapéutico , Terapia Neoadyuvante , Receptor ErbB-2 , Trastuzumab/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del TratamientoRESUMEN
PURPOSE: Previous studies show that fentanyl pectin nasal spray (FPNS) rapidly provides clinically meaningful pain relief in the treatment of breakthrough cancer pain (BTCP). This study assessed the long-term tolerability, acceptability and consistency of effect of FPNS in patients with BTCP. METHODS: Patients (new and rolled over from earlier controlled studies) with cancer experiencing one to four episodes per day of BTCP whilst taking ≥ 60 mg/day of morphine (or equivalent) given orally for cancer pain entered an open-label 16-week safety study. Safety and tolerability were assessed by adverse events (AEs), adverse drug reactions (ADRs), withdrawal due to AEs and by nasal assessments. Acceptability assessments included ratings of overall satisfaction with each treated episode and ease of use and convenience of FPNS. Additional rescue medication and dose stability were used to evaluate the consistency of effect. RESULTS: Four hundred three patients were included in the safety and intent-to-treat analysis (42,227 episodes), 356 entered the treatment phase and 110 completed 16 weeks. Overall, 24.6% of 403 patients reported treatment-related treatment-emergent AEs that were generally mild/moderate and typical of opioids; 20 patients discontinued treatment due to an AE (9 were ADRs). Nasal assessments revealed no clinically significant effects; 94% of FPNS-treated episodes required no additional rescue medication. More than 90% of patients did not have to increase their dose during the study. Patients reported overall satisfaction with FPNS for 90.1% of episodes. At week 12, 96.9% of patients were satisfied with the ease of use and 97.9% with the convenience of FPNS. CONCLUSIONS: FPNS was generally well tolerated and well accepted for the treatment of BTCP, and doses remained stable over the 4-month study period.
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Dolor Irruptivo/tratamiento farmacológico , Fentanilo/administración & dosificación , Neoplasias/complicaciones , Satisfacción del Paciente , Absorción , Administración Intranasal , Administración Oral , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/farmacocinética , Dolor Irruptivo/etiología , Femenino , Fentanilo/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Morfina/administración & dosificación , Mucosa Nasal/metabolismo , Rociadores Nasales , Dimensión del Dolor , Pectinas/administración & dosificación , Pectinas/farmacocinéticaRESUMEN
Limited proven treatment options exist for patients with metastatic breast cancer (MBC) resistant to anthracycline and taxane treatment. Ixabepilone, a novel semisynthetic analog of epothilone B, has demonstrated single-agent activity in MBC resistant to anthracyclines and taxanes. In combination with capecitabine in a phase III trial (CA163-046) in this setting, ixabepilone prolonged progression-free survival and increased objective response rate relative to capecitabine (Thomas et al. J Clin Oncol 25:5210-5217, 2007). Here, we report the results of overall survival (OS), a secondary efficacy endpoint from the CA163-046 trial. Seven hundred fifty-two patients with MBC resistant to anthracyclines and taxanes were randomized to ixabepilone (40 mg/m(2) intravenously on day 1 of a 21-day cycle) plus capecitabine (2,000 mg/m(2) orally on days 1 through 14 of a 21-day cycle) or capecitabine alone (2,500 mg/m(2) on the same schedule). Patients receiving ixabepilone plus capecitabine treatment had a median survival of 12.9 months compared to 11.1 months for patients receiving capecitabine alone (HR = 0.9; 95%CI: 077-1.05; P = 0.19). This observed increase in median OS favored the combination; however, the difference was not statistically significant. Predefined subset analyses showed a clinically meaningful increase in OS in KPS 70-80 patients receiving ixabepilone plus capecitabine (HR = 0.75; 95% CI: 0.58-0.98). Ixabepilone plus capecitabine did not show a significant improvement in survival compared to capecitabine alone in patients with MBC resistant to anthracyclines and taxanes. The observed differences in survival favored the combination arm. A clinical benefit was also seen in patients in the KPS 70-80 subgroup.
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Antraciclinas/uso terapéutico , Antibióticos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Resistencia a Antineoplásicos , Taxoides/uso terapéutico , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Asia , Neoplasias de la Mama/secundario , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Epotilonas/administración & dosificación , Europa (Continente) , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , América del Sur , Factores de Tiempo , Resultado del Tratamiento , Moduladores de Tubulina/administración & dosificación , Estados UnidosRESUMEN
INTRODUCTION: Pazopanib is approved in Latin America as first targeted therapy for patients with metastatic renal cell carcinoma (mRCC). METHODS: A retrospective chart review of adult patients with mRCC who initiated pazopanib as first targeted therapy between January 2011 and March 2016 was conducted among oncology care centers in Argentina, Brazil, Chile, Colombia, and Mexico. Patient characteristics, treatment patterns, overall survival (OS), progression-free survival (PFS), and adverse events were summarized. RESULTS: A total of 156 charts of patients with mRCC receiving first-line pazopanib were reviewed (29, 54, 27, 28, and 18 patients from Argentina, Brazil, Chile, Colombia, and Mexico, respectively). The mean age at initial mRCC diagnosis was 61.6 years, 73.7% were male, and 51.3% were Hispanic. The median dose of pazopanib was 800 mg and the median time from initial mRCC diagnosis to pazopanib start was 2.2 months. The median time on treatment was 10.0 months. At the time of data extraction, 16.7% of patients remained on pazopanib, with clinical progression listed as the main reason for discontinuation. Subsequent therapy was received by 25.6% of patients; the most common were everolimus (9.6%) and axitinib (5.8%). Overall, median PFS and OS were 10.8 and 16.9 months, respectively, and varied across countries. The most common all-grade adverse events were diarrhea (44.9%), asthenia/fatigue (43.6%), and nausea (28.8%). CONCLUSIONS: Pazopanib was used for first-line mRCC treatment in a clinically diverse patient population across Latin America. Real-world PFS and tolerability were similar to clinical studies of pazopanib. FUNDING: Novartis Pharmaceuticals Corporation, Inc.
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Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Anciano , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Progresión de la Enfermedad , Everolimus/uso terapéutico , Femenino , Humanos , Indazoles , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , América Latina , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pautas de la Práctica en Medicina , Supervivencia sin Progresión , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Estudios Retrospectivos , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Tiempo de TratamientoRESUMEN
INTRODUCTION: The purpose of this study was to evaluate the safety and efficacy of ixabepilone plus capecitabine in patients with metastatic or locally advanced triple-negative breast cancer (TNBC). PATIENTS AND METHODS: We conducted a pooled analysis of patients with TNBC enrolled in 2 phase III trials (NCT00080301 and NCT00082433), pretreated or resistant to an anthracycline and a taxane. In each study, patients were randomized to receive ixabepilone 40 mg/m2 (3-hour intravenous infusion, day 1), plus oral capecitabine 1000 mg/m2 twice daily (days 1-14), or capecitabine alone 1250 mg/m2 twice daily (days 1-14), every 3 weeks. Treatment was continued until disease progression or unacceptable toxicity. RESULTS: In the subset of patients with TNBC (N = 443), the addition of ixabepilone to capecitabine compared with capecitabine alone prolonged median progression-free survival from 1.7 months to 4.2 months (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.52-0.78; P < .0001), and doubled the objective response rate from 15% (95% CI, 10.4%-20.5%) to 31% (95% CI, 24.4%-38.0%). The median overall survival was similar (9.0 vs. 10.4 months; HR, 0.88; 95% CI, 0.72-1.08; P = .1802). A similar pattern of efficacy between arms was observed in the overall pooled population (N = 1973). The safety profile was comparable between the pooled TNBC subset and the overall pooled population. Adverse events observed with combination therapy were generally manageable and consistent with the safety profiles of the individual agents. CONCLUSION: Adding ixabepilone to capecitabine is effective in prolonging progression-free survival and improving objective response rate compared with capecitabine alone in patients with advanced TNBC previously treated with anthracyclines and taxanes.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Capecitabina/administración & dosificación , Epotilonas/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
BACKGROUND: Novel targeted agents and combinations have become available in multiple lines of treatment for human epidermal growth factor receptor 2-positive (HER2(+)) metastatic breast cancer (MBC). In this context, alternatives to the lapatinib (L) and capecitabine (C) regimen, evaluating L combined with other cytotoxic drugs, are warranted. PATIENTS AND METHODS: In the present phase II, multicenter study, patients with HER2(+) MBC with progression after taxane were randomized between L, 1250 mg, combined with C, 2000 mg/m(2) on days 1 to 14 (LC), vinorelbine (V), 25 mg/m(2) on days 1 and 8 (LV), or gemcitabine (G), 1000 mg/m(2) on days 1 and 8 (LG), every 21 days. The primary endpoint was the overall response rate. RESULTS: A total of 142 patients were included from 2009 to 2012. No differences were found in the patient baseline characteristics. The median age was 51 years, 69% were postmenopausal, 32% had liver metastasis, 57% were hormone receptor negative, and 48% had been previously treated with trastuzumab. The overall response rate was 49% (95% confidence interval [CI], 34.8%-63.4%), 56% (95% CI, 40%-70.4%), and 41% (95% CI, 27%-56.8%) in the LC, LV, and LG groups, respectively. The median progression-free survival was 9 months in the LC arm and 7 months in the other 2 arms (P = .28). The most common grade 3 and 4 adverse events were hand-foot syndrome (18%), diarrhea (6%), and increased alanine aminotransferase/aspartate aminotransferase (4%) in the LC arm; neutropenia (36%), diarrhea (9%), and febrile neutropenia (6%) in the LV arm; and neutropenia (47%), alanine aminotransferase/aspartate aminotransferase (13%), and rash (4%) in the LG arm. CONCLUSION: LV and LG seem to be active combinations in patients with HER2(+) MBC after taxane failure. The overall toxicity was manageable in all regimens.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Terapia Recuperativa/métodos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Lapatinib , Persona de Mediana Edad , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Receptor ErbB-2/biosíntesis , Taxoides/uso terapéutico , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/análogos & derivados , Vinorelbina , Adulto Joven , GemcitabinaRESUMEN
BACKGROUND: The aim of this multicenter phase II study was to demonstrate the activity of the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody cetuximab combined with irinotecan in the treatment of Latin American patients with EGFR-expressing metastatic colorectal cancer (mCRC) in whom previous treatment with an irinotecan-containing regimen had failed. PATIENTS AND METHODS: Patients received cetuximab, as a 400 mg/m2 initial infusion followed by 250 mg/m2 weekly, plus the same irinotecan regimen that had previously failed, until the occurrence of disease progression or unacceptable toxicity. The primary endpoint was response. Secondary endpoints included progression-free survival (PFS), duration of response, overall survival (OS), and safety. RESULTS: Seventy-nine patients received treatment. One patient had a complete response, 20 had partial responses, and disease was stabilized in 23 patients, giving an overall response rate of 27% and a disease control rate of 56%. The median duration of response was 23.9 weeks. Median PFS was 17.4 weeks, median OS was 9.2 months, and the 12-month OS rate was 38%. The most common adverse events according to System Organ Class were skin and subcutaneous tissue disorders (91% of the patients). Grade 3/4 adverse events occurred in 45 patients (57%), with the most common being diarrhea (20%), neutropenia (11%), and rash (6%). Seven patients (9%) had grade 3/4 acne-like skin rash. No grade 3/4 infusion-related reactions were reported. CONCLUSION: Cetuximab in combination with irinotecan is active and tolerable in Latin American patients with mCRC progressing on irinotecan, with a safety profile similar to that described in European studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Cetuximab , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Femenino , Humanos , Irinotecán , Masculino , Metástasis de la Neoplasia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Las metástasis óseas son un evento que se produce en el cáncer avanzado y pueden complicar la calidad de vida. Se presentan con dolor, fracturas patológicas, alteraciones neurológicas, hipercalcemia.
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Metástasis de la Neoplasia , Neoplasias ÓseasRESUMEN
PURPOSE: To evaluate the efficacy and safety of ixabepilone in patients with metastatic breast cancer (MBC) resistant to anthracycline, taxane, and capecitabine, in this multicenter, phase II study. PATIENTS AND METHODS: Patients with measurable disease who had tumor progression while receiving prior anthracycline, taxane, and capecitabine were enrolled. Ixabepilone 40 mg/m(2) monotherapy was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle. The primary end point was objective response rate (ORR), assessed by an independent radiology facility (IRF). RESULTS: A total of 126 patients were treated and 113 were assessable for response. Patients were heavily pretreated: 88% had received at least two lines of prior chemotherapy in the metastatic setting. IRF-assessed ORR was 11.5% (95% CI, 6.3% to 18.9%) for response-assessable patients. Investigator-assessed ORR for all treated patients was 18.3% (95% CI, 11.9% to 26.1%). Fifty percent of patients achieved stable disease (SD); 14.3% achieved SD >or= 6 months. Median duration of response and progression-free survival were 5.7 and 3.1 months, respectively. Median overall survival was 8.6 months. Patients received a median of 4.0 treatment cycles (range, one to 16 cycles), and 25% of patients received >or= eight cycles. Grade 3/4 treatment-related events included peripheral sensory neuropathy (14%), fatigue/asthenia (13%), myalgia (8%), and stomatitis/mucositis (6%). Resolution of grade 3/4 peripheral sensory neuropathy occurred after a median period of 5.4 weeks. CONCLUSION: Ixabepilone demonstrated clear activity and a manageable safety profile in patients with MBC resistant to anthracycline, taxane, and capecitabine. Responses were durable and notable in patients who had not previously responded to multiple prior therapies.
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Antraciclinas/farmacología , Antibióticos Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Desoxicitidina/análogos & derivados , Resistencia a Antineoplásicos , Epotilonas/uso terapéutico , Fluorouracilo/análogos & derivados , Taxoides/farmacología , Adulto , Anciano , Capecitabina , Desoxicitidina/farmacología , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/farmacología , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Resultado del TratamientoRESUMEN
PURPOSE: Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed to compare ixabepilone plus capecitabine versus capecitabine alone in anthracycline-pretreated or -resistant and taxane-resistant locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Seven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m(2) intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m(2) orally on days 1 through 14 of a 21-day cycle, or capecitabine alone 2,500 mg/m(2) on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review. RESULTS: Ixabepilone plus capecitabine prolonged progression-free survival relative to capecitabine (median, 5.8 v 4.2 months), with a 25% reduction in the estimated risk of disease progression (hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P = .0003). Objective response rate was also increased (35% v 14%; P < .0001). Grade 3/4 treatment-related sensory neuropathy (21% v 0%), fatigue (9% v 3%), and neutropenia (68% v 11%) were more frequent with combination therapy, as was the rate of death as a result of toxicity (3% v 1%, with patients with liver dysfunction [>/= grade 2 liver function tests] at greater risk). Capecitabine-related toxicities were similar for both treatment groups. CONCLUSION: Ixabepilone plus capecitabine demonstrates superior efficacy to capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Epotilonas/administración & dosificación , Fluorouracilo/análogos & derivados , Adulto , Anciano , Antraciclinas/uso terapéutico , Neoplasias de la Mama/mortalidad , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Progresión de la Enfermedad , Epotilonas/efectos adversos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Taxoides/uso terapéuticoRESUMEN
Objetivos: este estudio fue realizado para evaluar las recidivas locales y regionales, su relación con la respuesta completa patológica y la sobrevida de las pacientes co carcinoma localmente avanzado tratadas con quimioterapia neoadyuvante y tratamiento conservador de la mama. Materiales y métodos: estudio retrospectivo no randomizado, donde se evaluaron 35 pacientes con tumores de 5 cm o mayores, con axila positiva clínica en el 77% , que realizaron quimioterapia neoadyuvante (estadios IIB- IIIA- IIIB- IIIC) en el periodo entre 05/2003 y 12/2005 con una edad promedio de 52.68% (25-76) y un seguimiento medio de 42 meses (18-84). Todas realizaron cuadrantectomía y vaciamiento axilar. Conclusiones: el 20% de las pacientes presentó recidivas locales y regionales, que aparecieron al año de tratamiento. Se observaron un 8.57% de recidivas locales y regionales solas, en pacientes jóvenes con muy buena respuesta patológica. Las restantes recidivas se presentaron sincrónicamente con metástasis.Las pacientes menores de 39 años presentaron una sobrevida libre de enfermedad de 34%. La sobrevida libre de enfermedad fue de 54.83%, sobrevida global de 70.96%. La respuesta patológica completa fue del 9.00%, y la respuesta clínica completa del 34.28%. No se observó mayor beneficio en las pacientes que presentaron respuesta completa patológica, si leve mejoría en aquellas con respuesta anatomopatológica mayor del 95%, con p no significativa...