RESUMO
BACKGROUND: The randomised phase III TURANDOT trial compared first-line bevacizumab-paclitaxel (BEV-PAC) vs bevacizumab-capecitabine (BEV-CAP) in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). The interim analysis revealed no difference in overall survival (OS; primary end point) between treatment arms; however, progression-free survival (PFS) and objective response rate were significantly superior with BEV-PAC. We sought to identify patient populations that may be most appropriately treated with one or other regimen. METHODS: Patients with HER2-negative LR/mBC who had received no prior chemotherapy for advanced disease were randomised to either BEV-PAC (bevacizumab 10 mg kg(-1) days 1 and 15 plus paclitaxel 90 mg m(-2) days 1, 8 and 15 q4w) or BEV-CAP (bevacizumab 15 mg kg(-1) day 1 plus capecitabine 1000 mg m(-2) bid days 1-14 q3w). The study population was categorised into three cohorts: triple-negative breast cancer (TNBC), high-risk hormone receptor-positive (HR+) and low-risk HR+. High- and low-risk HR+ were defined, respectively, as having ⩾2 vs ⩽1 of the following four risk factors: disease-free interval ⩽24 months; visceral metastases; prior (neo)adjuvant anthracycline and/or taxane; and metastases in ⩾3 organs. RESULTS: The treatment effect on OS differed between cohorts. Non-significant OS trends favoured BEV-PAC in the TNBC cohort and BEV-CAP in the low-risk HR+ cohort. In all three cohorts, there was a non-significant PFS trend favouring BEV-PAC. Grade ⩾3 adverse events were consistently less common with BEV-CAP. CONCLUSIONS: A simple risk factor index may help in selecting bevacizumab-containing regimens, balancing outcome, safety profile and patient preference. Final OS results are expected in 2015 (ClinicalTrials.gov NCT00600340).
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Bevacizumab , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Fatores de RiscoRESUMO
Megestrol acetate (MA) has glucocorticoid activity and can induce significant secondary adrenal suppression. We designed this study to determine the extent of adrenal insufficiency in cancer patients receiving MA by utilising a sensitive low-dose adrenocorticotropin (ACTH) stimulation test. Adrenal function was assessed by a low-dose (0.625 microg) ACTH (1-24) stimulation test in 30 patients receiving MA for metastatic cancer. 10 of the patients who failed this test underwent a standard (250 microg) test on another day. Adrenal function was also evaluated in 15 of the patients by measuring the excretion of free cortisol in 24-h urine samples. Peak serum cortisol levels following stimulation with low-dose (0.625 microg) ACTH (1-24) were <18 microg/dl in 16 of 30 (53%) patients, of whom 9 had a basal serum cortisol level of <5 microg/dl. Five of 16 poor responders to the low-dose test showed normal stimulation with the standard (250 microg) ACTH (1-24) test. Thus, adrenal insufficiency would fail to be detected by the standard high dose test in these patients. Patients who failed the low-dose ACTH (1-24) test had lower 24-h urinary free cortisol excretion (8.7+/-10.3 microg/24 h) than normal responders (35+/-12.7 microg/24 h). Impaired adrenal function is common in cancer patients receiving MA. The low-dose ACTH (1-24) test is apparently capable of revealing adrenal insufficiency undetected by the standard high-dose ACTH test. Patients receiving MA might have inadequate adrenal function during episodes of infection or after withdrawal of MA therapy and this may require prompt corticosteroid treatment.
Assuntos
Insuficiência Adrenal/diagnóstico , Hormônio Adrenocorticotrópico , Acetato de Megestrol/efeitos adversos , Neoplasias/tratamento farmacológico , Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/metabolismo , Hormônio Adrenocorticotrópico/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Hidrocortisona/urina , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias/metabolismoRESUMO
A case of clear cell chondrosarcoma of the rib in a 30-year-old man is described. The tumor developed at the site of repetitive low-impact trauma (on the arm of a wheelchair) over a period of 24 years. An association between chondrosarcoma and external trauma has not been previously reported. Chondrosarcoma has been described in previously irradiated bone and in Paget's disease. In both these examples there is an increase in new bone formation associated with necrosis of bone and increased resorption of bone, respectively. A possible mechanism in our case is increased new bone formation elicited by repeated microfractures of trabeculae of rib bone.
Assuntos
Neoplasias Ósseas/etiologia , Condrossarcoma/etiologia , Costelas , Cadeiras de Rodas , Ferimentos não Penetrantes/complicações , Adulto , Neoplasias Ósseas/patologia , Condrossarcoma/patologia , Evolução Fatal , Humanos , Masculino , Paraplegia/complicações , Recidiva , Costelas/lesõesRESUMO
Spontaneous regression of pure seminoma metastases is a rare phenomenon, with only a few cases reported to date. To the best of our knowledge, this is the first report of regression of anaplastic pure seminoma metastases located in the retroperitoneum. We present a 27-year-old man, a marihuana smoker, with metastatic pure anaplastic seminoma in the high retroperitoneal lymph nodes. After orchiectomy, his metastases regressed with no medication. Several mechanisms are suggested to explain this phenomenon, which still remains elusive.
Assuntos
Regressão Neoplásica Espontânea , Neoplasias Retroperitoneais/secundário , Seminoma/secundário , Neoplasias Testiculares/patologia , Adulto , Humanos , Metástase Linfática , Masculino , Orquiectomia , Seminoma/cirurgia , Neoplasias Testiculares/cirurgiaRESUMO
Two patients with Kaposi's sarcoma developing in an area of lymphedematous arm postmastectomy are reported. The Kaposi's sarcoma occurred after latent periods of 26 and 7 years following radical and modified-radical mastectomy, respectively, in the edematous tissue of the ipsilateral arm. The cutaneous nodules were purple in color and ranged in size from a few millimeters to > 1 cm in diameter. The results of routine laboratory tests were all within normal limits. Human immunodeficiency virus (HIV) antibody and cytomegalovirus (CMV) antigen, using enzyme-linked immunosorbent assay (ELISA), were negative.
Assuntos
Mastectomia Radical , Segunda Neoplasia Primária/patologia , Sarcoma de Kaposi/patologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Carcinoma de Células Escamosas/patologia , Edema/etiologia , Feminino , Humanos , Neoplasias Cutâneas/patologia , Fatores de TempoRESUMO
A phase II study of carboplatin and etoposide as salvage polychemotherapy in metastatic, infiltrating breast carcinoma was carried out with 25 multiply pretreated patients. Six of 25 patients (24%) had a partial response that lasted an average of 3.5 months; of the six responders, four had undergone either four or five previous chemotherapeutic treatments. Eight of 25 patients (32%) had stable disease, and 11 (44%) manifested disease progression. The median survival from time of entry to the salvage protocol was 8 months. There were treatment responses in lung, chest wall, liver, and skeleton. The most common side effects were leukopenia (68% of 25 patients), thrombocytopenia (56%), anemia (40%), fever (28%), and weakness (16%). Carboplatin combined with etoposide may be an effective and tolerable salvage regimen in advanced breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Neoplasias da Mama/patologia , Carboplatina/administração & dosagem , Carcinoma Ductal de Mama/secundário , Etoposídeo/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Análise de SobrevidaRESUMO
A multicenter phase III randomized study compared the efficacies of two adjuvant polychemotherapeutic regimens in 145 patients with stage II node-positive breast cancer. The standard chemotherapy combination, CMF (cyclophosphamide, methotrexate, 5-fluorouracil), was administered to 77 women. The experimental protocol, CNF (cyclophosphamide, mitoxantrone, 5-FU), in which mitoxantrone (Novantrone) replaced methotrexate, was given to 68 patients. Follow-up of the 145 patients by six participating hospitals showed no statistically significant difference (p = 0.6) between the two treatment regimens during a median follow-up of 4.5 years in terms of overall survival. There was, however, a significant advantage (p = 0.04) in the disease-free survival for those receiving mitoxantrone (mean survival 4.4 years for CNF versus 2.7 years for CMF). Toxic side effects associated with CNF (particularly alopecia and myelotoxicity) were relatively more frequent but acceptable and did not lead to dose reduction. In light of its association with improved disease-free survival in this study, larger studies should be undertaken on the role of mitoxantrone as adjuvant treatment in stage II breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Metástase Linfática , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Estadiamento de Neoplasias , Análise de SobrevidaRESUMO
BACKGROUND: We report safety data from a randomised, phase III study (CECOG/BC.1.3.005) evaluating first-line bevacizumab plus paclitaxel or capecitabine for locally recurrent or metastatic breast cancer. PATIENTS AND METHODS: Patients aged ≥18 years with human epidermal growth factor receptor-2-negative breast adenocarcinoma were randomised to Arm A: bevacizumab 10 mg/kg days 1 and 15; paclitaxel 90 mg/m(2) days 1, 8, and 15, every 4 weeks; or Arm B: bevacizumab 15 mg/kg day 1; capecitabine 1000 mg/m(2) b.i.d., days 1-14, every 3 weeks, until disease progression, unacceptable toxicity or consent withdrawal. RESULTS: A post hoc interim safety analysis included 561 patients (Arm A: 284, Arm B: 277). The regimens demonstrated similar frequencies of all-grade and serious adverse events (SAEs), but different safety profiles. Treatment-related events occurred in 85.2% (Arm A) and 78.0% (Arm B) of patients. Fatigue was most common in Arm A (30.6% versus 23.5% Arm B), and hand-foot syndrome (HFS) most common in Arm B (49.5% versus 2.5% Arm A). Diarrhoea (Arm A: 0.4%, Arm B: 1.4%) and pulmonary embolism (Arm A: 0.7%, Arm B: 1.1%) were the most frequently reported SAEs. CONCLUSION: These findings are in-line with safety data for bevacizumab plus paclitaxel or capecitabine, reported in previous phase III trials.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Bevacizumab , Neoplasias da Mama/química , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Estudos Prospectivos , Receptor ErbB-2/análiseAssuntos
Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Toxidermias/etiologia , Dermatoses do Pé/induzido quimicamente , Dermatoses da Mão/induzido quimicamente , Paclitaxel/efeitos adversos , Adulto , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Feminino , Humanos , Paclitaxel/uso terapêutico , Síndrome , TrastuzumabRESUMO
The authors describe two cases of tamoxifen-induced organic delusional syndrome that resulted from administration of 40 mg daily for the adjuvant treatment of breast carcinoma. After discontinuation of the tamoxifen therapy, the psychiatric episode resolved within 2 to 4 weeks. Because tamoxifen might cause delusional syndrome, the authors recommend full psychiatric evaluation in appropriate cases.
Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Delusões/induzido quimicamente , Transtornos Relacionados ao Uso de Substâncias/etiologia , Tamoxifeno/efeitos adversos , Adenocarcinoma/cirurgia , Adulto , Idoso , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Mastectomia Radical Modificada , Transtornos Paranoides/induzido quimicamenteRESUMO
Disagreement persists on the necessity of axillary lymph node dissection for small T1 stage unilateral breast cancers. In this study of 120 women with T1 primary tumors who underwent extensive dissection, better definition of pathological factors that can predict axillary node metastases might have spared 88 (73.3%) who were node negative. We assessed age, tumor size, histology, grade and hormone receptor status as possible indicators of lymph node involvement. As expected, tumor size was a strong predictor of the likelihood of node involvement (p = 0.026 in univariate and p = 0.0024 in multivariate analyses). Progesterone receptor status also correlated significantly (p = 0.0008 in univariate and p = 0.017 in multivariate analyses) with axillary positivity. Tumor grade was found to be significant (p 0.018) only in univariate analysis. These findings contribute to the ongoing search for confident selection of subgroups of patients who will undergo lumpectomy but can safely be spared axillary node dissection.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Excisão de Linfonodo , Metástase Linfática/diagnóstico , Proteínas de Neoplasias/análise , Receptores de Progesterona/análise , Procedimentos Desnecessários , Adulto , Idoso , Axila , Neoplasias da Mama/química , Carcinoma Ductal de Mama/química , Carcinoma Lobular/química , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Receptores de Estrogênio/análise , Estudos RetrospectivosRESUMO
Chemotherapy and interleukin-2 (IL-2) and/or interferon alpha (IFN alpha) produce objective responses in a proportion of patients with advanced malignant melanoma. The duration of response to chemotherapy is usually less than 4 months, and immunotherapy has resulted in long-lasting remissions in a small number of patients with metastatic melanoma. The current study was conducted to improve the antitumor efficacy and the interactions between recombinant (r) IL-2, rIFN alpha 2a and chemotherapy. A total of 16 evaluable patients with metastatic malignant melanoma were entered into a phase-II study designed to assess the response rate and therapeutic efficacy of dacarbazine and carboplatin followed by rIL-2 and rIFN alpha 2a. Patients received 750 mg/m2 dacarbazine with 400 mg/m2 carboplatin each by intravenous bolus on days 1 and 22. Recombinant IL-2 and IFN alpha 2a were administered on an outpatient basis (home therapy) subcutaneously for 6 consecutive weeks: 4.8 x 10(6) IU/m2 rIL-2 daily, 5 days a week; 6.0 x 10(6) IU/m2 rIFN alpha 2a thrice weekly. There were responses in 6 of the 16 enrolled patients with an overall response rate of 37.5% (95% confidence interval: 14%-61%). All responding patients had partial responses. The median survival time of the responding patients was significantly better than that of patients with progressive and stable disease (P = 0.03). The median duration of response was 11 months (range 2-24 months). Responses in lung, liver, soft tissue and lymph-node sites were noted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Masculino , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes , Taxa de SobrevidaRESUMO
The therapeutic performance, effect on quality of life and cost effectiveness of an orally administered medication in a home care setting were examined prospectively in a group of 61 patients presenting with advanced colorectal carcinoma. A regimen of daily ftorafur capsules (370 mg/m2) and leucovorin tablets (20 mg/m2) was offered to 35 symptomatic patients with poor performance status; the standard in-hospital i.v. protocol of 5-fluouracil and leucovorin was given to the remaining 26 patients. Follow-up and survival analysis indicated that there was no compromise in survival associated with home care and oral chemotherapy. There were statistically significant advantages in terms of reduced toxicity and improved Karnofsky performance status in this group. Home care was approximately 70% less expensive. A home treatment program based on oral ftorafur may be the most desirable option for all patients with advanced colorectal carcinoma.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/economia , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/economia , Fluoruracila/economia , Tegafur/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Assistência Domiciliar/economia , Humanos , Avaliação de Estado de Karnofsky , Leucovorina/administração & dosagem , Leucovorina/economia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Tegafur/administração & dosagemRESUMO
Fourteen patients with advanced ovarian cancer who failed chemotherapy received a long-acting LHRH agonist. All the patients had been previously operated on and all had received at least one regimen of chemotherapy. Duration of decapeptyl administration was between 1 month and 28 weeks. There were no complete or partial responses. Eight patients (57%) had disease stabilization with a median progression-free interval of 14 weeks (range 4-28 weeks). All other patients developed a clear progressive cancer after the first injection of LHRH agonist. Three of these patients are still alive and receiving other forms of chemotherapy (median follow-up after the end of LHRH treatment was 11.5 months). The regimen was well tolerated with only mild toxicity observed (hot flushes in 2 patients). Although D-Trp-6-LHRH (Decapeptyl) was well tolerated, it had insignificant activity in treating patients with epithelial cancer that was resistant or relapsed after first-line platinum-based chemotherapy.
Assuntos
Neoplasias Ovarianas/tratamento farmacológico , Pamoato de Triptorrelina/uso terapêutico , Idoso , Carcinoma/tratamento farmacológico , Feminino , Humanos , Injeções Intramusculares , Pessoa de Meia-Idade , Terapia de Salvação , Falha de Tratamento , Pamoato de Triptorrelina/administração & dosagemRESUMO
Thirty-four evaluable patients with metastatic malignant melanoma were entered into a phase-II study designed to assess the response rate and analyze the long-term therapeutic efficacy of recombinant interferon (rIFN) alpha-2a and dacarbazine. Patients received 14 days of daily subcutaneous r-IFN alpha-2a (3 x 10(6) IU/day), followed by 9 x 10(6) IU on alternate days, as long as objective response lasted, in combination with i.v. dacarbazine started on day 7 (400 mg/m2) and repeated every 21 days (dacarbazine doses were escalated to 800 mg/m2). In 11 patients, 6 complete (17.6%) and 5 partial (14.7%) responses were seen, with an overall response rate of 32.3% (95% confidence interval: 16%-48%). The median survival time of the responding patients was significantly better than that of patients with progressive disease (P = 0.01) and the median response time of the patients showing complete response was longer than that of the partially responding patients (14 and 7 months respectively, P = 0.06).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dacarbazina/uso terapêutico , Interferon-alfa/uso terapêutico , Melanoma/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Distribuição de Qui-Quadrado , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Sinergismo Farmacológico , Feminino , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/secundário , Análise de SobrevidaRESUMO
Kaposi's sarcoma is a rare neoplasm of characteristic chronicity. The classical form which occurs most often in elderly men of Eastern European origin, comprises both an indolent, cutaneous type marked by spontaneous regression with prolonged survival, and a rarer, disseminated variant is more fulminant. Seven elderly Jewish patients with classical, disseminated, visceral Kaposi's sarcoma were studied; they were neither homosexual nor drug-abusers. All immunologic parameters were normal and serum tests for HIV antibodies, CMV, and EBV were negative. Five of these patients were treated and four responded well, including two complete remissions. The prolonged survival of these patients (82% at 5 years) suggests the existence of an indolent subtype or forme fruste of the usually aggressive form of classical Kaposi's sarcoma.