RESUMO
A number of HIV prevention interventions for male couples are in the pipeline for development as few evidence-based ones exist. Among these projects, none include all three groups of male couples (concordant HIV-negative, HIV-discordant, and concordant HIV-positive) as their target population, and only two are eHealth-based. The present qualitative study sought to assess whether one of the eHealth HIV prevention interventions for concordant HIV-negative male couples - called MCAP - could be adapted to meet the relationship and HIV prevention needs of HIV-discordant and HIV-positive male couples. Data for this study are drawn from in-person, individual-level interviews conducted with a convenience sample of 10 HIV-discordant male couples (n = 20) and 8 HIV-positive male couples (n = 16) from the Miami-Fort Lauderdale metro area in 2016. Thematic analysis was conducted to identify patterns (themes) of partners' thoughts about the toolkit, including how they perceived it could be improved for their own relationship and other couple's relationships. Two themes emerged from analysis of the qualitative data suggesting how the participants wanted the toolkit to be improved to meet their needs. Specifically, participants recommended for the toolkit to include guidance about integrating the use of biomedical HIV prevention strategies into couple's relationships, as well as for how partners can best take care of each other and further protect themselves from HIV and/or other STIs (Prevention Guidance). In addition, participants requested for the concept of sexual agreements to be broadened to include other aspects they deemed to be important in their life (e.g., mental health, exercise and nutrition) (Holistic agreements). Findings from the present study illuminate the ways in which MCAP would need to be adapted for these two groups of male couples in order to meet the needs for all three groups of male couples in the U.S. in a future iteration of this intervention.
Assuntos
Infecções por HIV/prevenção & controle , Promoção da Saúde/métodos , Homossexualidade Masculina/psicologia , Sexo Seguro/psicologia , Parceiros Sexuais/psicologia , Telemedicina/métodos , Adulto , Criança , Pré-Escolar , Infecções por HIV/diagnóstico , Infecções por HIV/psicologia , Humanos , Lactente , Entrevistas como Assunto , Masculino , Pesquisa QualitativaRESUMO
BACKGROUND: We determined the objective response rates produced by pegylated liposomal doxorubicin (PLD) plus carboplatin with/without trastuzumab (Herceptin). PATIENTS AND METHODS: Patients with measurable disease were stratified by taxane treatment history and human epidermal growth factor receptor-2 status. TREATMENT: PLD 30 mg/m(2) followed by carboplatin, day 1 of each 28-day cycle; human epidermal growth factor receptor-2 (HER2)-positive patients also received trastuzumab. RESULTS: Arm 1 received PLD plus carboplatin (N = 41 arm 1a, taxane naive; N = 42 arm 1b, taxane pretreated); Arm 2 patients received PLD plus carboplatin + Herceptin (N = 46). Overall response rates: 31%, 31%, and 56%, respectively. Median overall survival durations were not reached in arm 1a and were 13 and 33 months for arms 1b and 2. Median progression-free survival: 8, 5, 10 months, respectively. Grades 3-4 treatment-related toxic effects for arms 1a, 1b, 2, respectively, were neutropenia 22%, 31%, 35%; thrombocytopenia 34%, 26%, 17%; and fatigue 2%, 14%, 13%. CONCLUSIONS: PLD plus carboplatin has moderate antitumor activity and excellent tolerability. Herceptin and PLD plus carboplatin in HER2-positive patients have antitumor activity without significant cardiac toxicity. Toxicity results suggest that PLD can be combined with Herceptin with minimal cardiac toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carboplatina/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Humanos , Metástase Neoplásica , Polietilenoglicóis/administração & dosagemRESUMO
BACKGROUND: Systemic therapy options are limited for metastatic castration-resistant prostate cancer (CRPC) patients who progress following docetaxel (Taxotere). This phase II trial evaluated sunitinib malate in patients with progressing metastatic CRPC following prior docetaxel. PATIENTS AND METHODS: Patients with metastatic CRPC progressing following one to two chemotherapy regimens including docetaxel were included. The primary end point was progression-free survival (PFS) per radiographic and clinical evaluations. Oral sunitinib was administered 50 mg/day 4-weeks on followed by 2-weeks off per cycle up to a maximum of eight cycles or until clinical progression or intolerable toxicity. RESULTS: Thirty-six patients with a median age of 69.5 years were accrued. The median PFS was 19.4 weeks with a 12-week PFS of 75.8%. Four patients (12.1%) had a > or =50% prostate-specific antigen (PSA) decline and seven (21.2%) had a > or =30% PSA decline. Two of 18 patients (11.1%) with measurable disease demonstrated 30% declines by RECIST and eight (44.4%) displayed some shrinkage. A decline in pain score > or =2 points occurred in 13.6% of 22 assessable patients. Drug discontinuation due to toxic effects occurred in 52.8% of patients. CONCLUSION: Sunitinib malate demonstrated promising activity in metastatic CRPC progressing after prior docetaxel.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Castração , Indóis/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Pirróis/uso terapêutico , Taxoides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Intervalo Livre de Doença , Docetaxel , Humanos , Indóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Pirróis/efeitos adversos , Qualidade de Vida , Sunitinibe , Taxoides/efeitos adversos , Fatores de Tempo , Falha de TratamentoRESUMO
BACKGROUND: Platinum-based chemotherapy is the standard treatment for advanced gastric cancer (GC). This trial explored the efficacy and tolerability of combined docetaxel (Taxotere) + oxaliplatin (DOCOX) in GC patients. PATIENTS AND METHODS: Patients with untreated stage IV GC or adenocarcinoma of the gastroesophageal junction (AGEJ) received docetaxel 60 mg/m(2) followed by oxaliplatin 130 mg/m(2) on day 1 of each 21-day cycle until progression or unacceptable toxicity. The primary end points were response rate (RR), toxicity, progression-free survival (PFS), and overall survival (OS). RESULTS: Baseline characteristics (N = 71): median age 59 years, 72% male, 51% esophagogastric junction cancer, and Eastern Cooperative Oncology Group performance status of zero, one, two were 42%, 51%, 7%, respectively. The median number of cycles was 6 (range, 1-19). Grades 3-4 toxic effects: neutropenia (70%); vomiting (17%); nausea (16%); dehydration, fatigue, or diarrhea (13%, each); and thrombocytopenia or febrile neutropenia (7%, each). Sixty-six patients completed >/=2 cycles. The RR was 36% with 25 partial response (PR) and no complete responses (CRs); stable disease (SD) was 49%. Clinical benefit rate (CBR = CR + PR + SD >/=6 months) was 40%; median PFS was 4.3 months, and OS was 8.5 months. CONCLUSIONS: DOCOX produced manageable toxicity in patients with advanced GC and AGEJ. The confirmed RR of 36%, CBR of 40%, and median survival of 8.5 months are encouraging and comparable to standard front-line regimens.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Junção Esofagogástrica , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Gluconato de Cálcio/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Junção Esofagogástrica/patologia , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Sulfato de Magnésio/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Pré-Medicação , Neoplasias Gástricas/patologia , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do TratamentoRESUMO
The primary objective of these trials was to determine the 1-year survival of advanced non-small cell lung cancer (ANSCLC) patients (> or =70 years with PS 0-2 or > or =18 years with PS 2) receiving sequential paclitaxel and carboplatin (P --> C) or concurrent P + C. The secondary objectives were assessment of toxicities and quality of life. A total of 121 patients with NSCLC were treated. P--> C patients received paclitaxel (80 mg/m(2)) weekly x 3, followed by 1 week of rest; these 4-week cycles were repeated until relapse. At relapse, patients received carboplatin (AUC = 5, IV) on Day 1 of each 3-week cycle until evidence of further progression or lack of improvement. P + C patients received paclitaxel (80 mg/m(2)) and carboplatin (AUC = 2), weekly x 3, followed by 1 week of rest, until relapse. Patients in both studies were premedicated prior to paclitaxel administration. Sequential P + C resulted in a median survival of 8.2 months (range: <1-18.8) and P + C patients had a median survival of 9.2 months (range: <1-22.0). In both groups (P--> C) and P + C), the 1-year survival was 31%. For patients treated sequentially, treatment-related AEs (TRAE, > or =Grade 3) included fatigue (7%), neuropathy (5%), and leukopenia and diarrhea (3%, each). Grade 4 AEs were limited to neutropenia, febrile neutropenia, and sepsis (1 episode each). For patients receiving concurrent P + C, TRAE included neutropenia and leukopenia (15%, each) and shortness of breath and bilateral bone pain (10%, each). Leukopenia (n = 2) and neutropenia (n = 1) were the only Grade 4 events reported. The analysis of quality of life (QOL) questionnaires indicated that there were no obvious differences between treatment groups during the study. These drugs and treatment schema were well-tolerated when administered in the community setting and resulted in survival rates that were similar to what is reported in the literature with combination therapy administered to "high risk" patients. Finding the optimal chemotherapy regimen, that can be tolerated, remains a challenge in elderly patients.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/patologia , Masculino , Paclitaxel/efeitos adversos , Qualidade de Vida , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
UNLABELLED: This trial was designed to determine the 1-year survival rate, efficacy, and safety, produced by topotecan and gemcitabine as first line chemotherapy in advanced non-small cell lung cancer (ANSCLC). Fifty-three patients were enrolled; 51 received treatment. Topotecan 1 mg/m(2), days 1-5 and gemcitabine 1 g/m(2) days 1 and 15 were administered IV, each drug over 30 min; cycles consisted of 28 days. Treatment continued until progressive disease or intolerable toxicity. Nineteen patients (36%) had Eastern Cooperative Oncology Group criteria performance status (ECOG PS) = 0, 34 (64%) PS = 1. Median age was 64 years; 37 patients (70%) were male. HISTOLOGY: adenocarcinoma (42%), squamous cell carcinoma (28%), large cell (19%), and unclassified (11%). Among 47 evaluable patients, eight (17%) had partial response, 11 (23%) had stable disease. One-year survival was 39% and median survival was 7.6 months (range, < 1-19.6). Grade 3 and 4 toxicities included neutropenia (53%), anemia (18%), thrombocytopenia (12%), asthenia (8%), and gastrointestinal disorders (8%); three patients (6%) experienced neutropenic fever. There were no treatment-related deaths. The combination topotecan/gemcitabine produced a 1-year survival similar to previous platinum-based regimens, when used as first line chemotherapy for ANSCLC. The toxicity profile was acceptable.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Topotecan/administração & dosagem , Resultado do Tratamento , GencitabinaRESUMO
The purpose of this study was to assess the efficacy of weekly administration of docetaxel as a single agent in patients with hormone-refractory, symptomatic, metastatic prostate cancer with respect to symptom palliation, tumor response, time to progression, and survival. Sixty men with progressive metastatic prostate cancer that had progressed on at least one hormonal regimen were enrolled in this multicenter phase II study. Twenty-one percent of patients had received prior palliative radiotherapy, and 25% had received prior chemotherapy for hormone-refractory disease. Patients were scheduled to receive three 8-week cycles of docetaxel (36 mg/m(2) on days 1, 8, 15, 22, 29, and 36) with 2-week intervals between cycles. The docetaxel dose could be decreased in the event of toxicity, but no dose escalation was permitted. A > or =50% decrease in serum prostate-specific antigen (PSA) levels from baseline with stabilization or improvement of performance status lasting 2 months or longer occurred in 24 (41%) patients, of whom 16 (27%) had a > or =80% decrease for 2 months or more. The median time to progression for all patients was 5.1 months (range, 0.9 to 18.2 months). The estimated median time to progression for patients who had and those who did not have a > or =50% reduction in serum PSA level with stable or improved performance status was 6.65 and 4.3 months, respectively. The median overall survival was 9.4 months (range, 1.6 to 18.2 months). Treatment toxicity was considered acceptable. Single-agent docetaxel at 36 mg/m(2) weekly was associated with a PSA response rate of 41%, increased time to progression and survival, and minimal myelosuppression in patients with hormone-refractory metastatic prostate cancer.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Paclitaxel/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Taxoides , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Docetaxel , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Cuidados Paliativos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Análise de SobrevidaRESUMO
CCR5 is a CC chemokine receptor expressed on memory lymphocytes, macrophages, and dendritic cells and also constitutes the main coreceptor for macrophage-tropic (or R5) strains of human immunodeficiency viruses. In the present study, we investigated whether CCR5 was palmitoylated in its carboxyl-terminal domain by generating alanine substitution mutants for the three cysteine residues present in this region, individually or in combination. We found that wild-type CCR5 was palmitoylated, but a mutant lacking all three Cys residues was not. Through the use of green fluorescent fusion proteins and immunofluorescence studies, we found that the absence of receptor palmitoylation resulted in sequestration of CCR5 in intracellular biosynthetic compartments. By using the fluorescence recovery after photobleaching technique, we showed that the non-palmitoylated mutant had impaired diffusion properties within the endoplasmic reticulum. We next studied the ability of the mutants to bind and signal in response to chemokines. Chemokines binding and activation of G(i)-mediated signaling pathways, such as calcium mobilization and inhibition of adenylate cyclase, were not affected. However, the duration of the functional response, as measured by a microphysiometer, and the ability to increase [(35)S]guanosine 5'-3-O-(thio)triphosphate binding to membranes were severely affected for the non-palmitoylated mutant. The ability of RANTES (regulated on activation normal T cell expressed and secreted) and aminooxypentane-RANTES to promote CCR5 endocytosis was not altered by cysteine replacements. Finally, we found that the absence of receptor palmitoylation reduced the human immunodeficiency viruses coreceptor function of CCR5, but this effect was secondary to the reduction in surface expression. In conclusion, we found that palmitoylated cysteines play an important role in the intracellular trafficking of CCR5 and are likely necessary for efficient coupling of the receptor to part of its repertoire of signaling cascades.
Assuntos
Palmitatos/metabolismo , Receptores CCR5/metabolismo , Transdução de Sinais , Acilação , Sequência de Aminoácidos , Animais , Células CHO , Compartimento Celular , Membrana Celular/metabolismo , Quimiocina CCL5/farmacologia , Cricetinae , Cisteína/fisiologia , Citoplasma/metabolismo , Endocitose , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , HIV/metabolismo , Humanos , Dados de Sequência Molecular , Transporte Proteico , Receptores CCR5/genética , Receptores CCR5/fisiologia , Alinhamento de SequênciaRESUMO
PURPOSE: To determine outcomes in local-regional control, disease-free survival, and overall survival in patients with locally advanced breast cancer (LABC) who present with ipsilateral supraclavicular metastases and who are treated with combined-modality therapy. PATIENTS AND METHODS: Seventy patients with regional stage IV LABC, which is defined by our institution as LABC with ipsilateral supraclavicular adenopathy without evidence of distant disease, received treatment on three prospective trials of neoadjuvant chemotherapy. All patients received neoadjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil, or cyclophosphamide, doxorubicin, vincristine, and prednisone. Patients then received local therapy that consisted of either total mastectomy and axillary lymph node dissection (ALND) or segmental mastectomy and ALND before or after irradiation. Patients with no response to neoadjuvant chemotherapy were treated with surgery and/or radiotherapy. After completion of local therapy, chemotherapy was continued for four to 15 cycles, followed by radiotherapy. Patients older than 50 years who had estrogen receptor-positive tumors received tamoxifen for 5 years. RESULTS: Median follow-up was 11.6 years (range, 4.8 to 22.6 years). Disease-free survival rates at 5 and 10 years were 34% and 32%, respectively. The median disease-free survival was 1.9 years. Overall survival rates at 5 and 10 years were 41% and 31%, respectively. The median overall survival was 3.5 years. The overall response rate (partial and complete responses) to induction chemotherapy was 89%. No treatment-related deaths occurred. CONCLUSION: Patients with ipsilateral supraclavicular metastases but no other evidence of distant metastases warrant therapy administered with curative intent, ie, combined-modality therapy consisting of chemotherapy, surgery, and radiotherapy. Patients with ipsilateral supraclavicular metastases should be included in the stage IIIB category of the tumor-node-metastasis classification because their clinical course and prognosis are similar to those of patients with stage IIIB LABC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Radiografia , Análise de Sobrevida , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
The aim was to assess chemotherapy-induced histologic changes in breast cancer and to evaluate their relationship with tumour response, to treatment and patient survival. We examined paired pre- and post-chemotherapy tumour specimens from 57 patients with stages II and III breast cancers. All patients received three to four courses of anthracycline-containing preoperative treatment and subsequently underwent modified radical mastectomy 3-5 months after diagnosis. Histologic parameters evaluated included extent of residual disease and cytologic changes in residual tumour and in non-neoplastic breast tissue and lymph nodes. Correlation of pathologic changes with disease-free and overall survival was evaluated. Clinical evaluation indicated that 24% (n=14) of patients had a complete response, 53% (n=30) had a partial response, and 22% (n=13) had stable disease. Pathologic assessment revealed a complete response in 14% (n=8) of patients. Clinical and histologic complete responses were discordant in 35% of patients. Sixty-eight percent of tumours demonstrated moderate to severe cytologic changes in the cytoplasm and nucleus of neoplastic cells. These were characterized by increased overall cell size, cytoplasmic vacuolization, nuclear enlargement, multinucleation, and vesiculation of chromatin. Chemotherapy-induced histologic changes varied within a tumour and between patients. Tumour cytologic changes were significantly associated with histologic (p=0.03) as well as clinical (p=0.02) tumour response. Pathologic tumour response, but not histologic changes, was also a powerful predictor of overall survival and relapse-free survival. In the non-neoplastic glandular tissue, periductal and perilobular fibrosis and atrophy of lobular acini similar to those seen in postmenopausal breast tissue were noted. Changes in lymph nodes were characterized by lymphoid depletion and fibrosis with and without tumour metastasis. Chemotherapy-induced cytologic changes are frequently seen in neoplastic breast epithelium and correlate with response to treatment. Histologic confirmation of clinical tumour response to preoperative chemotherapy is necessary for accurate characterization of patients', response to treatment.
RESUMO
BACKGROUND: The purpose of the current study was to evaluate the objective response rate and possibility of breast-conserving surgery using neoadjuvant tamoxifen in the multimodality treatment, including surgery and radiotherapy, of elderly or frail patients with locally advanced breast carcinoma. METHODS: Forty-seven patients age > 75 years or age < 75 years with comorbid conditions and locally advanced breast carcinoma were treated with neoadjuvant tamoxifen (20 mg/day) for 3-6 months. This was followed by surgery and radiotherapy when feasible and adjuvant tamoxifen for 5 years or until disease recurrence. RESULTS: The median age of the patients was 72 years (range, 48-86 years). Approximately 22% had T3 lesions, 57% had T4 lesions, 22% were Stage II (AJCC Manual for Staging Cancer, 3rd edition), and 78% were Stage III. Eighty percent were estrogen receptor positive. After 6 months of treatment with neoadjuvant tamoxifen, a response rate of 47% was observed, including a complete response rate of 6%. Twenty-nine patients (62%) were rendered free of disease by surgery, including 5 with breast-conserving procedures. After a median follow-up of 40 months, 23 patients (49%) remained disease free. The median survival time had not been reached at the time of last follow-up. No major toxicity was observed, with the exception of one patient who developed a possible tamoxifen-related Stage I endometrial carcinoma. The estimated 2-year and 5-year progression free and overall survival rates were 50% and 41%, and 83% and 59%, respectively. CONCLUSIONS: The results of the current study show that neoadjuvant tamoxifen was effective in the treatment of elderly or frail patients with locally advanced breast carcinoma with estrogen receptor positive tumors, and resulted in a reasonable response rate, including complete responses and good overall survival.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Antagonistas de Estrogênios/uso terapêutico , Terapia Neoadjuvante , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma/patologia , Carcinoma/radioterapia , Carcinoma/cirurgia , Doença , Intervalo Livre de Doença , Neoplasias do Endométrio/induzido quimicamente , Antagonistas de Estrogênios/efeitos adversos , Estudos de Viabilidade , Feminino , Seguimentos , Idoso Fragilizado , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Receptores de Estrogênio/análise , Indução de Remissão , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Taxa de Sobrevida , Tamoxifeno/efeitos adversos , Resultado do TratamentoRESUMO
This study was performed to evaluate the first indicators of breast cancer recurrence in 1,145 patients treated at the University of Texas MD Anderson Cancer Center, between July 1973 and December 1980. Twenty patients were excluded due to incomplete data, resulting in a total number of 1,125 evaluable patients. Data collection included the first metastatic site and its means of detection (symptoms, self-examination, physical examination performed by a physician, and the results of blood and radiological tests). Whether recurrence was found at the scheduled follow-up visits or between the scheduled visits was also analyzed. Symptoms were the primary indicator of relapse for 648 cases (57.6% of the study population). An additional 361 cases (32.1% of the total group) were detected by self-examination or by physician-performed physical examination. Other investigations, e.g. bone scans, liver scans, chest X-rays, and blood tests, revealed recurrent disease in only 116 patients (10. 3% of the population). Among the 1,125 patients, 254 recurrences (22. 6% of the study population) were detected at the scheduled follow-up surveillance and, among these, 64.6% were found by history or physical examination. The distribution of metastatic sites and first indicators of metastases remained constant over time. The scheduled follow-up visits detected a mean of 25.9% of relapses during the first 36 months, while after 36 months only 16.3% of relapses were detected by systematic monitoring. There were no statistically significant differences in disease-free overall survival rates between symptomatic and asymptomatic patients at the time the first recurrence was detected. Moreover, the disease-free and overall survival rates appeared to be the same in symptomatic and asymptomatic patients, whether or not the recurrence was detected by a scheduled follow-up examination. Two conclusions emerged from the present study. Extensive, routine laboratory investigations are not justifiable following curative treatment of primary breast cancer, and it seems reasonable and cost-effective to reduce follow-up surveillance to careful history and physical examination only. The actual method of surveillance does not significantly affect the time interval to metastasis detection and seems inefficient. Clearly, more sensitive methods are needed for earlier detection of recurrent metastatic breast cancer. In addition, early detection of metastases would be even more valuable if more effective treatment modalities of recurrent or metastatic breast cancer were available.
Assuntos
Neoplasias da Mama/patologia , Metástase Neoplásica/diagnóstico , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/secundário , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico por imagem , Autoexame de Mama , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/secundário , Diagnóstico Diferencial , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Metástase Linfática , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/secundário , Metástase Neoplásica/diagnóstico por imagem , Exame Físico , Radiografia , Cintilografia , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/secundário , Análise de SobrevidaRESUMO
The purpose of the study was to determine the response rates (RR) and duration to second- and third-line chemotherapy programmes in patients with anthracycline-resistant breast cancer, utilizing various definitions of anthracycline resistance. This was a retrospective analysis performed on 1335 patients with metastatic breast cancer who participated in consecutive clinical trials of first line, anthracycline-containing combination chemotherapy (ACCC) at the University of Texas MD Anderson Cancer Center between July 1973 and April 1980. Anthracycline-resistant groups were identified using definitions of anthracycline resistance found in the literature: progressive disease as best response to ACCC (Group 1, n = 56 patients); progressive disease while receiving ACCC after an intervening response to the drug (Group 2, n = 84); progressive disease within 6 months of last dose of ACCC (Group 3, n = 233); and progressive disease within 12 months of last dose of ACCC (Group 4, n = 272). Second- and third-line therapies administered to these patients included methotrexate, doxorubicin, mitoxantrone, bisantrene, vinblastine, vindesine, melphalan, mitomycin, cisplatin, etoposide and others, but not taxanes. The distribution of patients' characteristics was similar between the four groups, as was the use of second- and third-line regimens. Response rate (RR) to second-line chemotherapy were 5% and 7.7% for Group 1 and Group 2 respectively. In contrast, RR to second-line chemotherapy were 21.6% and 15% for Group 3 and 4. The differences in response rate between the combination of Groups 1 and 2 and Groups 3 or 4 were significant (P = 0.005 and P = 0.04 respectively). These results indicate that strictly defined anthracycline resistance as defined in Groups 1 and 2 is associated with resistance to many other cytotoxic drugs. The definitions used in Groups 3 and 4 include many patients with responsive tumours, and a more favourable prognosis.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Resistencia a Medicamentos Antineoplásicos , Humanos , Pessoa de Meia-Idade , RecidivaRESUMO
BACKGROUND: The purpose of this study was to evaluate the clinical outcome of doxorubicin-based adjuvant chemotherapy in elderly breast cancer patients and to compare results in elderly patients with those in younger patients. PATIENTS AND METHODS: We retrospectively reviewed the records of all patients aged 50 years or older treated in trials of doxorubicin-based adjuvant chemotherapy between 1974 and 1988. Old age was not an exclusion criterion for these trials. Patient characteristics, hematologic and nonhematologic side effects, patterns of recurrence, and causes of death were determined for patients aged 50-64 years and for patients aged 65 years or older, and results were compared between these two groups. Kaplan-Meier survival curves were plotted, and tested by the generalized Wilcoxon test. RESULTS: A total of 390 patients aged 50 years or older were treated with doxorubicin-based adjuvant chemotherapy during the study period. Of these, 325 were aged 50-64 years (group 1), and 65 were aged 65 years or older (group 2). The median follow-up period for group 1 was 185 months (range 29-272+ months), and the median follow-up period for group 2 was 169 months (range 128-240+ months). There were no statistically significant differences between the two groups with respect to performance status, hormone receptor profile, tumor size, nodal status, or type of locoregional therapy. There also were no statistically significant differences between the two groups in recurrence patterns, disease-free survival, or overall survival. The granulocyte and platelet nadirs of cycles 1, 3, and 6 were similar between the two groups. No cumulative hematologic side effects were seen in either group. The occurrence of second malignancies was extremely low in both groups. In both groups, the majority of deaths were due to progression of disease. CONCLUSIONS: Adjuvant doxorubicin-based chemotherapy is well tolerated in elderly breast cancer patients who have good performance status and normal cardiac ejection fraction. Adjuvant doxorubicin-based chemotherapy in these patients results in disease-free and overall survival rates similar to those seen in younger patients.
Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/administração & dosagem , Fatores Etários , Idoso , Antineoplásicos/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Feminino , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Volume SistólicoRESUMO
No previous studies have evaluated the effect of body size and menopausal status at diagnosis on survival from inflammatory breast cancer (IBC). We evaluated whether obesity and menopausal status had an impact on IBC survival in a cohort of 177 female IBC patients seen from 1974 to 1993 at The University of Texas MD Anderson Cancer Center. Survival time was defined as time from diagnosis until death or censorship at last date of contact. We categorized women by body size by using the National Institutes of Health/National Heart, Lung, and Blood Institute's definitions of obesity as body mass index ((BMI) = weight in kg/(height in m)2) > or = 30, overweight as 25 < or = BMI < 30kg/m2, and normal/lean as BMI < 25 kg/m2. Cox proportional hazards analysis, adjusting for axillary lymph node involvement and chemotherapy protocol, revealed a modifying effect of menopausal status at diagnosis on the association between obesity and IBC survival (P = 0.02). Relative to postmenopausal women, premenopausal women had significantly worse survival (hazard ratio (HR) = 1.51, 95% confidence interval (CI) = 1.03-2.22). After stratifying by menopausal status, premenopausal obese women had non-significantly better survival than their leaner premenopausal counterparts (HR = 0.63, 95% CI = 0.34-1.15) while postmenopausal obese women had significantly worse survival than their leaner counterparts (HR = 1.86, 95% CI = 1.02-3.40). These findings suggest that factors associated with larger body size at diagnosis may contribute to shorter IBC survival among postmenopausal women but not premenopausal women, who were found to have poorer survival regardless of body size.
Assuntos
Neoplasias da Mama/patologia , Obesidade/complicações , Pós-Menopausa , Pré-Menopausa , Adulto , Idoso , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Inflamação , Pessoa de Meia-Idade , Fatores de Risco , Análise de SobrevidaRESUMO
PURPOSE: To compare prospectively the antitumor activity of single-agent paclitaxel to the three-drug combination of fluorouracil, doxorubicin, and cyclophosphamide (FAC) as neoadjuvant therapy in patients with operable breast cancer. PATIENTS AND METHODS: Patients with T1-3N0-1M0 disease were randomized to receive either paclitaxel (250 mg/m(2)) as 24-hour infusion or FAC in standard doses at every-3-week intervals. Each patient was treated with four cycles of preoperative chemotherapy. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after four cycles of induction chemotherapy. RESULTS: A total of 174 patients were registered, and 87 were randomized to each arm of the study. Clinical response, ie, complete and partial responses, was similar in both arms of the study. Three patients in the FAC arm and one patient in the paclitaxel subgroup had progressive disease. The extent of residual disease by intent-to-treat analysis at the time of surgery was similar between the two arms of the study. CONCLUSION: The results of this prospective study demonstrated that single-agent paclitaxel as neoadjuvant therapy has significant antitumor activity, and this was clinically comparable to FAC. Similar fractions of patients had clinical complete and partial responses, and very few patients had no response to either therapy. The value of alternate non-cross-resistant therapies as used in this protocol on the clinical course of this disease would require longer follow-up.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Estudos ProspectivosRESUMO
BACKGROUND: This review of children and adolescents with nonorbital soft-tissue sarcoma of the head and neck was undertaken to describe late sequelae of treatment, as manifested primarily by problems with statural growth, facial and nuchal symmetry, dentition, vision and hearing, and school performance. PROCEDURE: Four hundred sixty-nine patients entered the IRS-II and -III protocols with localized, nonorbital soft-tissue sarcomas of the head and neck from 1978 through 1987. Their overall survival rate was 53% (250/469) at 5 years. Two hundred thirteen patients were surviving relapse-free 5 or more years after diagnosis, for whom there were serial height measurements at 2 or more years after initiation of therapy. Their median age at diagnosis was 5 years; the median length of follow-up was 7 years. All received multiple-agent chemotherapy, and all but 3 received irradiation to the primary tumor volume. Sixty-eight percent of the tumors arose in cranial parameningeal sites, 22% in nonparameningeal sites, and 10% in the neck. We reviewed flow sheets submitted to the IRS Group Statistical Office to ascertain which late sequelae were recorded. RESULTS: One hundred sixty-four patients (77%) had one or more problems recorded. One hundred ninety of the two hundred thirteen patients (89%) were under 15 years of age at study entry, and at follow-up 92 (48%) had failed to maintain their initial height velocity, which had decreased by more than 25 percentile points from the original value. Thirty-six of the one hundred ninety patients (19%) were receiving growth hormone injections. Hypoplasia or asymmetry of tissues in the primary tumor site was reported in 74 patients, and 13 underwent reconstructive surgery. Poor dentition or malformed teeth were noted in 61 patients. Impaired vision developed in 37 patients, owing primarily to cataracts, corneal changes, and optic atrophy. Thirty-six patients had decreased hearing acuity, and 9 were fitted with hearing aids; 5 of these 9 had received cisplatin. Thirty-five patients were noted to have problems learning in school. Four patients developed a second malignancy (two sarcomas, one carcinoma, one leukemia). CONCLUSIONS: Late sequelae affected the majority of these patients treated for soft-tissue sarcoma of the head and neck on IRS-II and -III. The potential impact of certain sequelae could be reduced by specific measures, such as surgical reconstruction and hormonal therapy. Late sequelae must be taken into account in designing future curative treatments.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia/efeitos adversos , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/radioterapia , Sarcoma/tratamento farmacológico , Sarcoma/radioterapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Sintomas Comportamentais/etiologia , Criança , Pré-Escolar , Face/efeitos da radiação , Traumatismos Faciais/induzido quimicamente , Feminino , Seguimentos , Crescimento/efeitos dos fármacos , Crescimento/efeitos da radiação , Transtornos da Audição/etiologia , Humanos , Lactente , Recém-Nascido , Deficiências da Aprendizagem/etiologia , Masculino , Segunda Neoplasia Primária/etiologia , Sarcoma de Ewing/tratamento farmacológico , Doenças da Glândula Tireoide/etiologia , Dente/efeitos dos fármacos , Dente/efeitos da radiação , Transtornos da Visão/etiologiaRESUMO
In this study we examined the clinical characteristics of relapse before and after complete clinical response (CR) to anthracycline-based combination chemotherapy in metastatic breast cancer (MBC). Our goal was to determine whether similar clinical trends could be observed during first relapse and relapse after CR. Two hundred and sixty-three patients with MBC were identified who had achieved CR after anthracycline-based combination chemotherapy for first recurrence. From this group, 226 patients had relapse after CR after a minimum follow-up of 13 years. Clinical features of their disease at first relapse and after progression from CR (second relapse) were examined, including disease-free interval (DFI) from diagnosis until first relapse, sites of recurrence, response to subsequent therapy, and survival after progression from CR. There was a significant correlation between duration of CR and survival after progression from CR. Patients who relapsed < 12 months after achieving CR had a median survival of 8.8 months after second relapse, whereas those who relapsed beyond 3 years had a median survival of 21.5 months (p = 0.0034). Neither the duration of CR nor length of survival after second relapse was related to the length of initial DFI. Patients with a short duration of CR (< 12 months) more often experienced second recurrences at multiple sites and in visceral organs (62% and 75%, respectively) than did patients with prolonged CR (> 36 months) (27% and 45%, respectively, p < 0.001). The anatomic location of metastatic disease at the time of first and second relapses was similar within a CR duration group but different among the groups. Short CR duration was associated with more frequent recurrence at visceral sites and also with chemotherapy-resistant second relapse. In conclusion, prolonged CR is associated with long survival after second relapse; however, neither CR duration nor survival after second relapse is related to the length of initial DFI. This suggests that chemotherapy, when it induces CR, may change the pace of disease progression. The tissue pattern of recurrence appears to be similar between first and second relapse, suggesting that the cellular predilection for metastatic sites has been preserved.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/patologia , Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Análise de Sobrevida , SobreviventesRESUMO
This review was performed to determine the efficacy of commonly used cytotoxic agents in the management of anthracycline-resistant breast cancer, using a stringent and uniform definition of drug resistance. We reviewed the reports of second- and third-line chemotherapy after anthracycline-containing regimens published over the last two decades. Only studies with sufficient information on the timing of progressive disease in relation to anthracycline therapy were considered. All assessable studies were reviewed individually, and the data obtained with taxanes in anthracycline-resistant breast cancer were also pooled to estimate the activity. The great majority of published studies on second- and third-line chemotherapy lack useful information about anthracycline resistance. Among the few studies with sufficient information about anthracycline resistance, several definitions were used. We reanalyzed those reports utilizing a uniform definition of anthracycline resistance: progression while receiving an anthracycline. Only studies using paclitaxel or docetaxel reported an activity in this anthracycline-resistant population, allowing a response rate between 6-50% and 32-57% for both agents respectively. The activity of other cytotoxic agents in anthracycline-resistant breast cancer could not be determined because a lack of accurate data using the stringent definition. Both paclitaxel and docetaxel have substantial antitumor activity in patients with clearly defined anthracycline-resistant breast cancer. The activity of other cytotoxic agents in this group of patients remains to be established.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Taxoides , Antraciclinas/administração & dosagem , Ensaios Clínicos como Assunto , Docetaxel , Feminino , Humanos , Paclitaxel/administração & dosagem , Paclitaxel/análogos & derivados , Resultado do TratamentoRESUMO
PURPOSE: We and others have demonstrated the antineoplastic efficacy of paclitaxel as a single agent in metastatic breast cancer. We performed this phase I trial to evaluate the combination of paclitaxel with doxorubicin. PATIENTS AND METHODS: Eligible patients had measurable or evaluable metastatic breast cancer for which this was the initial cytotoxic treatment. They may have received adjuvant chemotherapy with other drugs. The study had four parts. In part 1, the patients received paclitaxel by 24-hour infusion followed by doxorubicin by 48-hour infusion. The paclitaxel dose was to be escalated from a starting dose of 125 mg/m2, and the doxorubicin dose was to remain constant at 60 mg/m2 with treatment repeated every three weeks. The results of part 1 prompted part 2 which was a study of the reverse sequence. Part 3 was a formal study of pharmacology and has been reported (J Clin Oncol 14: 2713-21, 1996). In part 4, patients received doxorubicin 50 mg/m2 by bolus followed by paclitaxel 150 mg/m2 by 24-hour infusion for courses 1 and 2. In all subsequent courses doxorubicin was administered by 48-hour infusion. All patients in all four parts of the study had baseline cardiac scans. All patients received standard premedication for paclitaxel. RESULTS: Forty-eight patients were treated in all four parts of the study. In part 1 (10 patients), the maximum tolerated dose (MTD) was paclitaxel 125 mg/m2/24 hours followed by doxorubicin 48 mg/m2/48 hours as defined by dose-limiting mucositis and neutropenic fever which occurred at the starting dose. For part 2 (21 patients), the MTD was doxorubicin 60 mg/m2/48 hours followed by paclitaxel 160 mg/m2/24 hours. In part 4 (seven patients), the MTD was doxorubicin 50 mg/m2/bolus followed by paclitaxel 135 mg/m2/24 hours. In parts 2 and 4, the dose-limiting toxic effect was neutropenia. Of the entire cohort of 48 patients, seven (15%) had a complete response (one persists at five years without intervening therapy), 26 (54%) had a partial response for an objective response rate of 69% (95% confidence interval (95% CI): 54%-81%). The median follow-up of all living patients is 38+ months (range 20+ to 62+); the median response duration is seven months (range 2-33.7+); the median overall survival is 20.5 months (range 5-54+). The median time to progression is 9.6 months (range 1-33.7+ months). Two patients developed congestive heart failure, one at 24 months after her final dose of doxorubicin which amounted to a cumulative lifetime total doxorubicin dose of 870 mg/m2, one after a total of 660 mg/m2. In both, cardiac symptoms were controlled with medications. CONCLUSIONS: The combination of paclitaxel/24 hours with doxorubicin/48 hours is an effective antineoplastic treatment for metastatic breast cancer. However, the incidence of complete response, the median overall survival, and time to progression were not greater than for standard doxorubicin-based combinations. Additionally, a sequence-dependent interaction between paclitaxel and doxorubicin, given in the schedule described here, was defined. Other strategies and schedules should be evaluated to maximize the antineoplastic efficacy of these two potent agents.