RESUMO
In premenopausal women with hormone dependent breast cancers, ovarian suppression is an important part of treatment, and is often achieved with a bilateral salpingo-oophorectomy (BSO). However, this procedure can lead to ovarian remnant syndrome (ORS), a rare condition where the adnexal tissue is not completely removed and can produce estrogen. We describe a case of ORS in a patient with estrogen receptor positive (ER+) breast cancer who had progression of disease after undergoing a BSO, despite optimal therapy. ORS therefore poses a significant treatment challenge in premenopausal ER+ breast cancer patients thought to be rendered menopausal with a BSO.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Neoplasias Hepáticas/secundário , Ovariectomia/efeitos adversos , Adulto , Anastrozol/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estrogênios/metabolismo , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Doenças Ovarianas/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptor ErbB-2 , SíndromeRESUMO
BACKGROUND: Dual anti-HER2 therapy is effective for HER2-amplified breast cancer. Weekly paclitaxel, trastuzumab, and full-dose lapatinib (PTL) is not feasible because of grade 3 diarrhea. We conducted a phase II feasibility study of dose-dense (DD; every other week) PTL (ClinicalTrials.gov identifier, NCT01827163). PATIENTS AND METHODS: Eligible patients had HER2-positive breast cancer, tumor size ≤ 3 cm, and negative nodes. Treatment included paclitaxel (175 mg/m(2) × 4, every 2 weeks with pegfilgrastim), trastuzumab (4 mg/kg load and then 2 mg/kg weekly), and lapatinib (1000 mg daily). After paclitaxel × 4, trastuzumab (6 mg/kg every 3 weeks) plus lapatinib were continued for 1 year. The primary endpoint was feasibility, defined as (1) > 80% of patients completing PTL without a dose delay or reduction, (2) grade 3 diarrhea rate < 20%, and (3) cardiac event rate < 4%. RESULTS: From May 2013 to November 2013, we enrolled 20 of 55 planned patients. The median age was 49 years (range, 34-74 years). One patient had immediate paclitaxel hypersensitivity and was deemed inevaluable. Only 13 of 19 evaluable patients (68%) completed PTL without a dose delay or reduction or unacceptable toxicities. Only 3 of 19 (16%) had grade 3 diarrhea. Rash was frequent, with all grades in 18 of 19 (95%) and grade 3 in 2 of 19 (11%). The study was stopped early because of excess toxicity. CONCLUSION: The discontinuation rate during DD PTL was high, owing, in part, to an unexpectedly high incidence of rash. The trial was halted, because the initial discontinuation rate from overall toxicity made it unlikely that full accrual would demonstrate feasibility.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Lapatinib , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Projetos Piloto , Prognóstico , Quinazolinas/administração & dosagem , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Trastuzumab/administração & dosagemRESUMO
PURPOSE: To evaluate the efficacy and toxicity of erlotinib plus bevacizumab in patients with metastatic breast cancer (MBC), targeting the epidermal growth factor receptor (EGFR/HER1) and the vascular endothelial growth factor (VEGF) pathway. EXPERIMENTAL DESIGN: Thirty-eight patients with MBC were enrolled and treated at two institutions with erlotinib, a small molecule EGFR tyrosine kinase inhibitor (150 mg p.o. daily) plus bevacizumab, an anti-VEGF antibody (15 mg/kg i.v. every 3 weeks). Patients had one to two prior chemotherapy regimens for metastatic disease. The primary end point was response rate by Response Evaluation Criteria in Solid Tumors criteria using a Simon 2-stage design. Secondary end points included toxicity, time to progression, response duration, and stabilization of disease of > or = 26 weeks. Correlative studies were done on tumor tissue, including EGFR expression and mutation analysis. RESULTS: One patient achieved a partial response for 52+ months. Fifteen patients had stable disease at first evaluation at 9 weeks; 4 of these patients had stable disease beyond 26 weeks. Median time to progression was 11 weeks (95% confidence interval, 8-18 weeks). Diarrhea of any grade was observed in 84% of patients (grade 3 in 3%); 76% experienced grade 1 or 2 skin rash, and 18% developed hypertension (grade 3 in 11%). The level of EGFR expression was not predictive of response to therapy. CONCLUSIONS: The combination of erlotinib and bevacizumab was well-tolerated but had limited activity in unselected patients with previously treated MBC. Biomarkers are needed to identify those MBC patients likely to respond to anti-EGFR/HER1 plus anti-VEGF therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Bevacizumab , Cloridrato de Erlotinib , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: To determine the immediate and long-term effects of true acupuncture versus sham acupuncture on hot flash frequency in women with breast cancer. PATIENTS AND METHODS: Seventy-two women with breast cancer experiencing three or more hot flashes per day were randomly assigned to receive either true or sham acupuncture. Interventions were given twice weekly for 4 consecutive weeks. Hot flash frequency was evaluated at baseline, at 6 weeks, and at 6 months after initiation of treatment. Patients initially randomly assigned to the sham group were crossed over to true acupuncture starting at week 7. RESULTS: The mean number of hot flashes per day was reduced from 8.7 (standard deviation [SD], 3.9) to 6.2 (SD, 4.2) in the true acupuncture group and from 10.0 (SD, 6.1) to 7.6 (SD, 5.7) in the sham group. True acupuncture was associated with 0.8 fewer hot flashes per day than sham at 6 weeks, but the difference did not reach statistical significance (95% CI, -0.7 to 2.4; P = .3). When participants in the sham acupuncture group were crossed over to true acupuncture, a further reduction in the frequency of hot flashes was seen. This reduction in hot flash frequency persisted for up to 6 months after the completion of treatment. CONCLUSION: Hot flash frequency in breast cancer patients was reduced following acupuncture. However, when compared with sham acupuncture, the reduction by the acupuncture regimen as provided in the current study did not reach statistical significance. We cannot exclude the possibility that a longer and more intense acupuncture intervention could produce a larger reduction of these symptoms.
Assuntos
Acupuntura/métodos , Neoplasias da Mama/terapia , Fogachos/terapia , Neoplasias da Mama/complicações , Feminino , Fogachos/etiologia , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Sobreviventes , Resultado do TratamentoRESUMO
Many patients being treated for cancer use dietary supplements, particularly antioxidants, in the hope of reducing the toxicity of chemotherapy and radiotherapy. Some researchers have claimed, furthermore, that antioxidants also increase the effectiveness of cytotoxic therapy and have explicitly recommended their use. However, mechanistic considerations suggest that antioxidants might reduce the effects of conventional cytotoxic therapies. Preclinical data are currently inconclusive and a limited number of clinical studies have not found any benefit. Clinicians should advise their patients against the use of antioxidant dietary supplements during chemotherapy or radiotherapy. Such caution should be seen as the standard approach for any unproven agent that may be harmful.
Assuntos
Antineoplásicos/administração & dosagem , Antioxidantes , Suplementos Nutricionais , Neoplasias/terapia , Radioterapia , Antioxidantes/efeitos adversos , Terapia Combinada , Contraindicações , Humanos , Neoplasias/mortalidade , Taxa de SobrevidaRESUMO
PURPOSE: This study was designed to evaluate the efficacy and safety of single-agent gemcitabine for the treatment of patients with anthracycline- and taxane-pretreated metastatic breast cancer (MBC). Eligible patients were required to have bidimensionally measurable MBC that had been treated with 2-4 prior chemotherapy regimens that included an anthracycline and a taxane. Gemcitabine was delivered at a dose of 800 mg/m2 on days 1, 8, and 15 of a 28-day cycle until evidence of disease progression. PATIENTS AND METHODS: Twenty-two patients were enrolled and included in the safety analysis; 18 patients were evaluable for response. The median age of patients was 54 years (range, 36-70 years). The mean number of prior chemotherapy regimens for metastatic disease was 2.3, and the mean dose of gemcitabine delivered was 911 mg/m2 (range, 600-1600 mg/m2). RESULTS: Overall, gemcitabine was well tolerated with minimal grade 3 toxicities; the only grade 4 toxicity was 1 case of pulmonary embolus. Three patients had evidence of partial tumor regression (17%; 95% CI, 4%-41%), and 1 patient had a 41% decrease in tumor volume, including liver metastasis. CONCLUSIONS: Gemcitabine is active and well tolerated as monotherapy given in heavily pretreated patients with MBC after anthracyclines and taxanes. The activity and safety reported in this trial are consistent with previous reports in similar patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Terapia de Salvação , Adulto , Idoso , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Neoplasias Cutâneas/secundário , Neoplasias de Tecidos Moles/secundário , Análise de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento , Vômito/induzido quimicamente , GencitabinaRESUMO
PURPOSE: To develop a potentially superior adjuvant chemotherapy regimen, we conducted a pilot study of dose-dense 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by weekly alternating taxanes. The primary objective was to determine the feasibility of the regimen; the secondary objective was to estimate the disease-free and overall survival. EXPERIMENTAL DESIGN: Patients with >/=4 node-positive breast cancer were studied. Treatment consisted of FEC at 500/100/500 mg/m(2), respectively, x6 at two-week intervals with granulocyte colony-stimulating factor, followed by weekly paclitaxel (80 mg/m(2)) alternating with docetaxel (35 mg/m(2)) x18. RESULTS: Between November 2001 and January 2003, 44 patients were enrolled. Median age was 46 years (range, 26-63 years), median number of positive nodes was 9 (range, 4-32), and median tumor size was 2.5 cm (range, 0.6-11.0 cm). Because of unexpected toxicities, the study was stopped when 17 (39%) had fully completed all of the planned treatment. Two of 17 (12%) developed grade 4 pericardial/grade 3 bilateral pleural effusions at treatment completion; both required pericardial window. The remaining patients were treated with taxanes using one of several standard dose and schedule combinations. Furthermore, 4 of 44 (9%) developed pneumonitis attributed to the FEC regimen. Hospital admissions were required for 12 of 44 (27%); 3 of 44 (7%) required blood transfusions. There were no treatment related deaths. Median disease-free and overall survival will not be estimatable because of early closure of study. CONCLUSION: FEC x6 at 2-week intervals followed by 18 weeks of alternating taxanes is not feasible at the doses tested. Other strategies are needed to improve adjuvant systemic chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linfonodos/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Projetos Piloto , Fatores de Risco , Taxa de Sobrevida , Taxoides/administração & dosagemRESUMO
PURPOSE: Preclinical studies demonstrate a link between overexpression of HER-2/neu and cyclooxygenase-2 (COX-2) activity. To explore the possibility that COX-2 is a therapeutic target, we conducted a phase II study of celecoxib, a selective COX-2 inhibitor, and trastuzumab in patients with HER-2/neu-overexpressing metastatic breast cancer that had progressed while receiving trastuzumab. EXPERIMENTAL DESIGN: Eligible patients had bi-dimensionally measurable or evaluable HER-2/neu-overexpressing metastatic breast cancer. HER-2/neu overexpression, defined as 2+ or 3+ by the HercepTest, was required. Patients had to have progressed despite prior trastuzumab-based therapy. Treatment consisted of celecoxib (400 mg twice daily) and trastuzumab. RESULTS: Twelve patients were enrolled (42% status post 1 regimen for metastatic disease 58% status post > 2 prior regimens (range of 2-6). Eleven patients were evaluable. There were no responses. Median duration of treatment was 9 weeks. One patient had stable disease at 3 months but progressed at 6 months. A second patient stopped treatment at 3 months because of unresolved grade 2 rash, felt to be related to celecoxib. Toxicities were generally grade 1 or 2. One patient (8%) experienced grade 3 toxicity (abdominal pain). CONCLUSIONS: Celecoxib combined with trastuzumab is well tolerated. However, this combination in patients with HER2/neu-overexpressing, trastuzumab-refractory disease, was not active.