RESUMO
Ninety-six assessable patients with advanced or recurrent uterine sarcomas, who were no longer controllable with surgery and radiotherapy, and who had not received prior chemotherapy were treated with cisplatin 50 mg/m2 intravenously every 3 weeks. Of 63 cases with mixed mesodermal tumors, five complete responses (CRs; 8%) and seven partial responses (PRs; 11%) were observed (95% confidence interval [CI], 10.3% to 30.9%). Of 33 patients with leiomyosarcoma, one PR (3%) was observed (95% CI, .1% to 15.8%). Adverse effects included leukopenia (23%), nausea and vomiting (73%), and mild azotemia (42%). No patients experienced life-threatening toxicity. Cisplatin has definite activity when given at the dose and schedule that we tested for patients with mixed mesodermal sarcomas who have not received prior chemotherapy, but has little activity in patients with leiomyosarcoma.
Assuntos
Cisplatino/uso terapêutico , Leiomiossarcoma/tratamento farmacológico , Sarcoma/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/efeitos adversos , Avaliação de Medicamentos , Feminino , Humanos , Leiomiossarcoma/patologia , Pessoa de Meia-Idade , Prognóstico , Sarcoma/patologia , Análise de Sobrevida , Neoplasias Uterinas/patologiaRESUMO
PURPOSE: From 1979 to 1984, 356 eligible patients with advanced or recurrent endometrial carcinoma no longer amenable to therapy with surgery, radiotherapy, or progestins were treated with doxorubicin alone or doxorubicin in combination with cyclophosphamide. PATIENTS AND METHODS: Patients were randomized to receive doxorubicin 60 mg/m2 intravenously (i.v.) with or without cyclophosphamide 500 mg/m2 i.v. every 3 weeks for eight drug courses. All patients had received prior therapy with progestins with subsequent progression of disease. No patients had received prior therapy with cytotoxic drugs. Of 356 patients, 300 had measurable disease. RESULTS: Among 132 patients treated with doxorubicin alone, there were seven complete responses (5%), 22 partial responses (17%), 73 with stable disease (55%), and 30 with increasing disease within 2 months of study entry (23%). For the 144 patients who received the combination, there were 18 complete responses (13%), 25 partial responses (17%), 75 with stable disease (52%), and 26 with increasing disease (18%). The median progression-free interval for those patients who received doxorubicin alone was 3.2 months, while it was 3.9 months for those who received the combination. The median survival duration for doxorubicin patients was 6.7 months, while it was 7.3 months for the combination patients. None of the unadjusted estimates of treatment differences are statistically significant. Prognostic features that had an impact on outcome included one factor associated with an increased likelihood of response (presence of measurable lung metastases) and four features associated with a poorer survival (poor performance status [PS] of 2 or 3, high pathologic grade, and presence of liver metastases or other intraabdominal disease). If these features are taken into account in multivariate analyses, there is no statistically significant evidence for differences in response rates (relative odds of response, 1.58; P = .06, one-tailed test), and survival duration is slightly longer in the combination regimen (17% reduction in death rate; P = .048). CONCLUSION: The combination of doxorubicin plus cyclophosphamide thus appears to offer a small advantage over doxorubicin alone in the management of endometrial carcinoma at the expense of more frequent and severe myelosuppression and gastrointestinal toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Doxorrubicina/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/secundário , Carcinoma Adenoescamoso/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Neoplasias do Endométrio/patologia , Feminino , Humanos , Infusões Intravenosas , Metaplasia/tratamento farmacológico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: This Gynecologic Oncology Group (GOG) trial of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) as salvage therapy for recurrent epithelial carcinoma of the ovary sought to confirm activity reported previously. If positive, the trial was to serve as a basis for phase III trials of Taxol in combination with platinum compounds in first-line therapy. PATIENTS AND METHODS: Patients with recurrent, persistent, or progressive ovarian carcinoma during or after platinum-based chemotherapy received Taxol 170 mg/m2 intravenously once over 24 hours every 3 weeks. All patients had measurable disease and received premedication (dexamethasone, diphenhydramine, and ranitidine) followed by Taxol. RESULTS: Of 49 patients, 45 were eligible and assessable. Among 43 patients who were assessable for response, there were eight complete and eight partial responses (37%). The median progression-free interval was 4.2 months, and median survival 16 months. Among 27 resistant patients who progressed during or within 6 months of prior platinum-based therapy or had stable disease as the best response, five complete (18%) and four partial (15%) responses were observed (33%). The median progression-free interval was 4 months. Among 16 sensitive patients who responded and progressed more than 6 months after prior platinum-based treatment, three complete (19%) and four partial (25%) responses were observed (44%). The median progression-free interval was 4.9 months. Grade 4 neutropenia (< 500/microL), the most frequent and severe toxicity, occurred in 73% of patients. Other hematologic effects were less frequent and less severe. Cardiac problems and hypersensitivity reactions were observed in one patient each. CONCLUSION: Taxol is a highly active agent in ovarian carcinoma, even in patients who are clinically resistant to platinum-based chemotherapy, and produces frequent and severe, albeit manageable, myelosuppression. It is clearly active as salvage therapy for ovarian carcinoma.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Compostos de Platina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Resistência a Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neoplasias Ovarianas/mortalidade , Paclitaxel/efeitos adversos , Indução de Remissão , Terapia de Salvação , Taxa de Sobrevida , Estados UnidosRESUMO
PURPOSE: Progestins have definite activity against advanced or recurrent endometrial carcinoma. Both parenteral and oral progestins yield similar serum levels and response rates, which range from 18% to 34%. The one major study that used oral medroxyprogesterone acetate (MPA) noted a response rate at the lower end of the range (18%) and much poorer progression-free and overall survival times (4 and 10.5 months, respectively) than previously reported. The present study sought to confirm this earlier study of oral MPA, to assess the importance of prognostic factors such as histologic grade and receptor levels, and to determine whether a higher dose of MPA would yield a higher response rate. PATIENTS AND METHODS: Two hundred ninety-nine eligible women with advanced or recurrent endometrial carcinoma were randomized to receive oral MPA either 200 mg/d or 1, 000 mg/d until unacceptable toxicity intervened or their disease progressed. RESULTS: Among 145 patients receiving the low-dose regimen, there were 25 complete (17%) and 11 partial (8%) responses for an overall response rate of 25%. The 154 patients receiving the high-dose regimen experienced 14 (9%) complete and 10 (6%) partial responses for an overall response rate of 15%. Median durations of progression-free survival were 3.2 months and 2.5 months for the low-dose and high-dose regimens, respectively. Median survival durations were 11.1 months and 7.0 months, respectively. The adjusted relative odds of responding to the high-dose regimen compared with the low-dose regimen was 0.61 (90% confidence interval, 0.36 to 1.04). Prognostic factors having a significant impact on the probability of response included initial performance status, age, histologic grade, and progesterone receptor concentration. Compliance with oral therapy was documented with serum levels 1 month after starting therapy, when possible. MPA levels were commensurate with the assigned dose and schedule. CONCLUSION: Oral MPA is active against endometrial carcinoma. Response to progestin therapy is more frequent among patients with a well-differentiated histology and positive progesterone receptor status. This study provides no evidence to support the use of MPA 1,000 mg/d orally instead of MPA 200 mg/d orally. In fact, the trends suggest the opposite. The use of oral MPA 200 mg/d is a reasonable initial approach to the treatment of advanced or recurrent endometrial carcinoma, particularly those lesions that are well-differentiated and/or progesterone receptor-positive (> 50 fmol/mg cytosol protein). Patients with poorly differentiated and/or progesterone receptor levels less than 50 fmol/mg cytosol protein had only an 8% to 9% response rate.
Assuntos
Antineoplásicos Hormonais/administração & dosagem , Carcinoma/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Acetato de Medroxiprogesterona/administração & dosagem , Administração Oral , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/sangue , Carcinoma/sangue , Carcinoma/diagnóstico , Carcinoma/metabolismo , Carcinoma/mortalidade , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Acetato de Medroxiprogesterona/efeitos adversos , Acetato de Medroxiprogesterona/sangue , Pessoa de Meia-Idade , Prognóstico , Receptores de Progesterona/metabolismo , Recidiva , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Because toxicities associated with chemotherapy and radiotherapy can adversely affect short- and long-term patient quality of life, can limit the dose and duration of treatment, and may be life-threatening, specific agents designed to ameliorate or eliminate certain chemotherapy and radiotherapy toxicities have been developed. Variability in interpretation of the available data pertaining to the efficacy of the three United States Food and Drug Administration-approved agents that have potential chemotherapy- and radiotherapy-protectant activity-dexrazoxane, mesna, and amifostine-and questions about the role of these protectant agents in cancer care led to concern about the appropriate use of these agents. The American Society of Clinical Oncology sought to establish evidence-based, clinical practice guidelines for the use of dexrazoxane, mesna, and amifostine in patients who are not enrolled on clinical treatment trials. METHODS: A multidisciplinary Expert Panel reviewed the clinical data regarding the activity of dexrazoxane, mesna, and amifostine. A computerized literature search was performed using MEDLINE. In addition to reports collected by individual Panel members, all articles published in the English-speaking literature from June 1997 through December 1998 were collected for review by the Panel chairpersons, and appropriate articles were distributed to the entire Panel for review. Guidelines for use, levels of evidence, and grades of recommendation were reviewed and approved by the Panel. Outcomes considered in evaluating the benefit of a chemotherapy- or radiotherapy-protectant agent included amelioration of short- and long-term chemotherapy- or radiotherapy-related toxicities, risk of tumor protection by the agent, toxicity of the protectant agent itself, quality of life, and economic impact. To the extent that these data were available, the Panel placed the greatest value on lesser toxicity that did not carry a concomitant risk of tumor protection. RESULTS AND CONCLUSION: Mesna: (1) Mesna, dosed as detailed in these guidelines, is recommended to decrease the incidence of standard-dose ifosfamide-associated urothelial toxicity. (2) There is insufficient evidence on which to base a guideline for the use of mesna to prevent urothelial toxicity with ifosfamide doses that exceed 2.5 g/m(2)/d. (3) Either mesna or forced saline diuresis is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide use in the stem-cell transplantation setting. Dexrazoxane: (1) The use of dexrazoxane is not routinely recommended for patients with metastatic breast cancer who receive initial doxorubicin-based chemotherapy. (2) The use of dexrazoxane may be considered for patients with metastatic breast cancer who have received a cumulative dosage of 300 mg/m(2) or greater of doxorubicin in the metastatic setting and who may benefit from continued doxorubicin-containing therapy. (3) The use of dexrazoxane in the adjuvant setting is not recommended outside of a clinical trial. (4) The use of dexrazoxane can be considered in adult patients who have received more than 300 mg/m(2) of doxorubicin-based therapy for tumors other than breast cancer, although caution should be used in settings in which doxorubicin-based therapy has been shown to improve survival because of concerns of tumor protection by dexrazoxane. (5) There is insufficient evidence to make a guideline for the use of dexrazoxane in the treatment of pediatric malignancies, with epirubicin-based regimens, or with high-dose anthracycline-containing regimens. Similarly, there is insufficient evidence on which to base a guideline for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease. (6) Patients receiving dexrazoxane should continue to be monitored for cardiac toxicity. Amifostine: (1) Amifostine may be considered for the reduction of nephrotoxicity in patients receiving cisplatin-based chemoth
Assuntos
Amifostina/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Mesna/uso terapêutico , Substâncias Protetoras/uso terapêutico , Protetores contra Radiação/uso terapêutico , Razoxano/uso terapêutico , Adulto , Antineoplásicos/efeitos adversos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Radioterapia/efeitos adversosRESUMO
The protein c-erbB-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsies from women diagnosed with malignant tumors. Present studies suggest that soluble fragments of the c-erbB-2 oncogene may be released from the cell surface and become detectable in patients with carcinoma of the breast. Consequently, the purpose of this study was to assay the c-erbB-2 protein in the saliva and serum of women with and without carcinoma of the breast and to determine whether the protein possesses any diagnostic value. To determine the diagnostic utility of this oncogene, the soluble form of the c-erbB-2 protein was assayed in the saliva and serum using ELISA in three different groups of women. The three groups consisted of 57 healthy women, 41 women with benign breast lesions, and 30 women diagnosed with breast cancer. To compare the relative diagnostic utility of the c-erbB-2 protein, CA 15-3 was also measured. The CA 15-3 measurements served as a "gold standard" by which to compare the c-erbB-2 protein's diagnostic effectiveness. We found c-erbB-2 protein in the saliva and serum of all three groups of women. The salivary and serological levels of c-erbB-2 in the cancer patients, however, were significantly higher (P < 0.001) than the salivary and serum levels of healthy controls and benign tumor patients. Additionally, the c-erbB-2 protein was found to be equal to or to surpass the ability of CA 15-3 to detect patients with carcinoma. The results of the pilot study suggest that the c-erbB-2 protein may have potential use in the initial detection and/or follow-up screening for the recurrence of breast cancer in women.
Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/metabolismo , Receptor ErbB-2/biossíntese , Receptor ErbB-2/sangue , Saliva/metabolismo , Adulto , Análise de Variância , Área Sob a Curva , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Carcinoma/sangue , Carcinoma/metabolismo , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Matriz Extracelular/metabolismo , Feminino , Humanos , Metástase Linfática , Programas de Rastreamento , Menopausa , Pessoa de Meia-Idade , Mucina-1/biossíntese , Mucina-1/sangue , Projetos Piloto , Sensibilidade e Especificidade , FumarRESUMO
105 patients with advanced ovarian cancer previously treated with cisplatin or carboplatin were entered into a study of iproplatin as second-line therapy. Patients were either clinically resistant to cisplatin or carboplatin, or had relapsed after complete response to these agents. Patients were treated intravenously at an initial dosage of 270 mg/m2 with dosage adjustments to 340, 200 or 135 based on observed toxicity. Of 101 eligible patients, 7 responses (3 complete, 4 partial; 12%) were observed in 60 patients resistant to cisplatin. 2 partial responses (11%) occurred in 18 patients resistant to carboplatin. 2 complete and 3 partial responses were observed in 19 patients (26%) previously treated with but not resistant to cisplatin. Response durations were 2-20 months. Toxicities of iproplatin included thrombocytopenia in 93% of patients, leukopenia in 76% of patients, anaemia in 68% of patients, and diarrhoea in 40% of patients. Thus iproplatin shares cross-resistance with cisplatin and carboplatin in the treatment of ovarian cancer and is not recommended as an effective second-line agent for platinum-resistant ovarian cancer.
Assuntos
Antineoplásicos/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Resistência a Medicamentos , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversosRESUMO
Until the mid-1970s, standard therapy for ovarian carcinoma was a single alkylating agent. Subsequently, combination chemotherapy was shown to be superior to such therapy. During the 1980s, cisplatin-based combination chemotherapy became the standard chemotherapy regimen for advanced ovarian cancer; however, other classes of agents with documented activity against ovarian tumors appeared to be cross-resistant with platinum. The introduction of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the early 1990s, with its apparent lack of cross-resistance with platinum compounds, was a notable advance in ovarian cancer management that dramatically altered the standard of care. During the 1990s, the combination of platinum (cisplatin or carboplatin) plus paclitaxel rapidly evolved into front-line chemotherapy for advanced ovarian cancer. The series of randomized phase III studies that have compared the activity of platinum/paclitaxel with alternative regimens, including the previous standard combination of cisplatin/cyclophosphamide, support the combination of platinum/paclitaxel as the current standard chemotherapy for advanced ovarian cancer. Outstanding issues that stem from this phase III experience include the impact of nonprotocol salvage regimens on survival and the potential benefits of sequential single-agent regimens.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Neoplasias Ovarianas/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia de SalvaçãoRESUMO
No effective screening test for ovarian carcinoma exists. Consequently, only 25% of patients have limited (FIGO stage I-II) disease, and most of these will be at high risk for recurrence. Management requires categorization of the primary neoplasm as low or high risk. Those at low risk have all the following characteristics: grade I disease limited to the ovary, no tumor on the surface of the ovary, negative peritoneal cytology, and no ascites. The 5-year disease-free survival rate exceeds 90%; hence, surgical resection (total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and careful surgical exploration) followed by observation is the treatment of choice. Patients at high risk have one or more of the following features: grade 2 or 3 disease, disease outside of the ovary, tumor on the surface of the ovary, positive peritoneal cytology, or ascites. Recurrence rates approximate 40%. Platinum-based adjuvant chemotherapy yields a recurrence rate approximately half that obtained with no adjuvant therapy.
Assuntos
Neoplasias Ovarianas/terapia , Feminino , Humanos , Neoplasias Ovarianas/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de SobrevidaRESUMO
High-dose chemotherapy supported by bone marrow transplantation is being seriously investigated as a way to increase response and prolong survival in women with ovarian carcinoma. This report is a broad review of attempts over the past several years to demonstrate advantages of the high-dose approach. The existing data for dose escalation, short of doses requiring hematopoietic stem-cell transplant, demonstrate increased response rates, but no survival advantage. When even higher doses of chemotherapy are used in concert with autologous transplant to combat hematologic toxicities, even higher response rates have been reported. Despite this, all survival data from these later studies are limited. There is some hint of survival benefit in certain populations, such as those women with limited disease or perhaps in more advanced disease that has not been previously treated. All of the studies taken as a whole effectively demonstrate the need for randomized trials to address the issue of whether this approach provides any advantage over standard-dose chemotherapy. Future efforts at studying high-dose chemotherapy and autologous transplantation for ovarian carcinoma should be focused in this area; until results are available from such trials, high-dose chemotherapy with transplant will remain an experimental procedure.
Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Neoplasias Ovarianas/tratamento farmacológico , Medula Óssea/efeitos dos fármacos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Ensaios Clínicos como Assunto , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Resultado do Tratamento , Estados UnidosRESUMO
Maximum surgical effort will yield improved survival and response to subsequent therapy in patients with minimal residual disease (less than 2 cm diameter of any remaining nodule). Systemic therapy is the mainstay of later management. Studies have focused on single-agent v combination chemotherapy, optimal combination, dose intensity, and route of administration. In advanced disease, studies of the Gynecologic Oncology Group (GOG) demonstrate the superiority of cisplatin based combination chemotherapy over a single alkylating agent in regard to overall response, clinical complete response, response duration, and survival. Subsequent GOG and other studies suggest that a two-drug combination of cisplatin and cyclophosphamide is therapeutically equivalent to more toxic three- and four-drug combinations. Whether continued escalation of drug dose intensity beyond usual clinical schedules yields incremental gain in benefit remains under study. Administration of drug, particularly cisplatin, via the intraperitoneal (IP) route produces objective responses in patients who have progressed after prior cisplatin based therapy. Whether IP therapy is superior to IV therapy as first-line treatment is under investigation. In limited disease, patients can be assigned to low- and high-risk groups based on careful surgical staging. Patients with low-risk limited disease have a 5-year disease-free survival exceeding 95% with no adjuvant therapy. Those with high-risk disease, even with IP chromic phosphate or systemic melphalan, have a relapse rate of 20% or more after a similar period. The potential role of cisplatin based combination therapy in such patients is under study. Future improvement in results depends on current investigations of noninvasive methods for diagnosis and evaluation, better definition of the value of greater dose intensity and alternate route of administration, the value of methods for choosing appropriate drugs, the development of new agents, and methods to overcome drug resistance.
Assuntos
Carcinoma/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/cirurgia , Terapia Combinada , Feminino , Humanos , Neoplasias Ovarianas/cirurgiaRESUMO
The vast majority of patients with cervix carcinoma present with either preinvasive or minimally invasive (stage IA) disease and are cured with surgery alone. The remaining patients can be classified into two groups: those with disseminated (extrapelvic) disease at the time of presentation or recurrence after initial treatment and those with advanced pelvic disease. In the first group, the goal of therapy is palliative and the principal modality is chemotherapy. A number of single agents have significant activity (> or = 15% response rate): the platinum compounds, certain alkylating agents, the anthracyclines, bleomycin, the vinca alkaloids, certain antifols, 5-fluorouracil, 5'-floxuridine, ICRF-159, hexamethylmelamine, and CPT-11. Although uncontrolled trials report high response rates with combination regimens, no such regimen has been shown to be superior to single-agent therapy. The current standard of care for initial treatment is single-agent cisplatin 50 to 100 mg/m2 every 3 weeks, with an expected 23% response rate. In the second group, palliation takes the form of prevention of recurrence. Patients who have stage IIIB or IVA disease benefit from the addition of concomitant chemotherapy to radiation. The current standard of care is hydroxyurea 80 mg/kg orally twice weekly during radiotherapy. For patients with stage IB or II disease, surgery and/or radiotherapy remains the standard of care. Although concomitant or neoadjuvant chemotherapy followed by either surgery or radiotherapy has been evaluated, no conclusive evidence proves the value of the addition of chemotherapy to the management of these patients. Ongoing phase III trials are evaluating both approaches.
Assuntos
Cuidados Paliativos , Neoplasias do Colo do Útero/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/secundário , Ensaios Clínicos como Assunto , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/patologiaRESUMO
Epithelial carcinoma of the ovary is characterized by presentation at an advanced stage, spread primarily by an intraperitoneal (IP) route, and relative sensitivity to chemotherapy. An initial surgical approach is essential to proper staging of the disease process and to aggressive cytoreduction, which in turn improves response to chemotherapy and survival. The use of chemotherapy is the mainstay of definitive therapy after completion of the initial surgery. A large number of drugs have activity against the disease, with the most important single category of agents being the platinum compounds. Studies by the Gynecologic Oncology Group (GOG) document the superiority of cisplatin-based combination chemotherapy over single alkylating agents and combinations that do not include cisplatin. The current regimen of choice is a two-drug combination of cisplatin plus cyclophosphamide. Efforts to improve results further focus on enhancing dose intensity of the drug combination through either escalating intravenous (IV) doses or administering cisplatin via an IP route. Also offering an opportunity for further improvement of therapeutic results are three drugs identified as having activity in patients no longer candidates for cisplatin: carboplatin, ifosfamide, and taxol. Biologic agents, such as alpha-interferon, also have potential roles in future combination therapy. The management of patients with limited (stage I or II) disease is based on studies of the GOG and the Ovarian Cancer Study Group, which indicate that this population can be divided by prognostic factors into a group at low risk for recurrence and a group at high risk. Those at low risk require only surgery, whereas those at high risk should receive either IP radioactive chromic phosphate or systemic chemotherapy following surgery. The future prospects for additional improvement of results in all patients appear bright on the basis not only of studies of dose intensity and IP therapy but also of efforts directed at overcoming multidrug resistance and at devising noninvasive means of assessing disease status.
Assuntos
Carcinoma/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Previsões , Humanos , Injeções Intraperitoneais , PrognósticoRESUMO
The interactions of cancer and malnutrition are discussed with the focus on aging. To establish whether the elderly are more likely to develop cancer cachexia and its complications, this review encompasses the pathogenesis of malnutrition in cancer; the age-related alterations of appetite, gastrointestinal function, energy expenditure, and protein turnover; the diagnosis of malnutrition; and the effectiveness of nutritional support in the elderly. Although metabolic and physiologic changes induced by cancer and age appear synergistic in causing cachexia, more frequent complications of malnutrition have not been observed in the geriatric cancer patients. This may be due to only a small proportion of the elderly with cancer being enrolled in clinical studies or to a reduced cachexia-inducing ability of tumors in these patients. A limited number of studies indicate nutritional replenishment is obtainable in malnourished elderly by hyperalimentation. As restoration of the lean body mass may be slower in older patients, early institution of nutritional support is recommended in malnourished elderly or elderly at risk for malnutrition during neoplastic treatment.
Assuntos
Envelhecimento , Caquexia/etiologia , Neoplasias/complicações , Distúrbios Nutricionais/complicações , Idoso , Composição Corporal , Peso Corporal , Caquexia/fisiopatologia , Caquexia/terapia , Sistema Digestório/fisiopatologia , Comportamento Alimentar , Feminino , Glicólise , Humanos , Pessoa de Meia-Idade , Neoplasias/metabolismo , Neoplasias/fisiopatologia , Neoplasias/terapia , Distúrbios Nutricionais/diagnóstico , Nutrição Parenteral Total , Estudos Prospectivos , Proteínas/metabolismo , Risco , Fatores Socioeconômicos , PaladarRESUMO
The interrelationships of diet and carcinogenesis are discussed with the focus on aging. To establish whether the elderly are more susceptible to dietary carcinogens and whether dietary prevention of cancer is a reasonable goal for this population, the mechanisms of chemical carcinogenesis, the age-related metabolic and physiologic changes, and the current cancer preventive dietary strategies are reviewed. Vulnerability to dietary carcinogens results from a combination of factors that may increase or decrease the occurrence of cancer in the elderly, and it is, therefore, a very individualized feature, unpredictable when based solely on a subject's age. Dietary prevention of cancer may be effective in advanced age, and the dietary guidelines of the National Academy of Sciences should be implemented in this population.
Assuntos
Envelhecimento , Dieta , Neoplasias/etiologia , Aflatoxinas/toxicidade , Idoso , Carcinógenos/toxicidade , Carcinógenos Ambientais/toxicidade , Reparo do DNA/efeitos dos fármacos , Gorduras na Dieta/efeitos adversos , Fibras na Dieta/administração & dosagem , Etanol/toxicidade , Humanos , Mutagênicos/toxicidade , Neoplasias/induzido quimicamente , Neoplasias/prevenção & controle , Nitrosaminas/toxicidade , Obesidade/complicações , Selênio/uso terapêutico , Vitaminas/uso terapêuticoRESUMO
To determine the roles of radionuclide brain scanning and computerized tomography of brain in the pretreatment evaluation of patients with primary and locoregional recurrence of breast cancer, we reviewed the clinical and radiologic findings in 226 patients with breast cancer who underwent one of these scans either preoperatively or within 6 weeks of operation and in 34 patients presenting with locoregional recurrence. Four of 131 radionuclide brain scans in primary breast cancer suggested calvarial metastasis, and the findings were confirmed with bone scans and skull radiographs. One of 95 computerized tomographic scans of the brain showed brain metastasis, and this patient had profound neurologic deficits. With respect to locoregional recurrence, the results of 2 of 23 radionuclide scans and 1 of 11 computerized tomographic scans were positive. All three patients had clinical evidence for brain metastasis. We conclude that in the absence of signs and symptoms, routine evaluation for brain metastasis is not justified in primary and locoregional recurrence of breast cancer.
Assuntos
Neoplasias Encefálicas/secundário , Neoplasias da Mama/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Humanos , Mastectomia , Cuidados Pré-Operatórios , Radiografia , CintilografiaRESUMO
Thirty-eight patients with advanced or recurrent squamous cell carcinoma of the cervix no longer amenable to management with surgery and/or radiotherapy were given piperazinedione 9 mg/m2 intravenously every 3 weeks. Five (13%) experienced either complete or partial regression of disease, while 13 (34%) demonstrated stable disease. Responses were relatively short (median 3 months) with responders surviving significantly longer than nonresponders (median 20.3 months vs. 3.0 months, p = 0.01). Adverse effects consisted primarily of myelosuppression (61%) and nausea and vomiting (47%) and generally were mild to moderate and tolerable. The drug has minimal activity and tolerable adverse effects and could be considered for trials of combination chemotherapy in this disease.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Piperazinas/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Antibióticos Antineoplásicos/efeitos adversos , Avaliação de Medicamentos , Feminino , Humanos , Contagem de Leucócitos , Leucopenia/induzido quimicamente , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Piperazinas/efeitos adversos , Trombocitopenia/induzido quimicamenteRESUMO
Thirty-seven patients with advanced or recurrent adenocarcinoma of the ovary no longer amenable to control with surgery, radiation therapy, or higher prior chemotherapy were treated with cis-platinum, 50 mg/m2 intravenously every 3 weeks. Among the 37 patients, three patients had a clinical complete response (8%) and six had a partial response (16%). Twenty-three demonstrated stable disease (62%), while five demonstrated rapidly increasing disease (14%). Median response duration was 5 months and median survival was 10+ months. Responders survived longer than nonresponders (p = 0.01). Adverse effects included leukopenia (26/37), thrombocytopenia (19/37), nausea and vomiting (35/37), and azotemia (19/37). Adverse effects were generally mild to moderate and tolerable. Cis-platinum thus appears to be highly active in the treatment of adenocarcinoma of the ovary at the dose and schedule tested.
Assuntos
Adenocarcinoma/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Cisplatino/efeitos adversos , Avaliação de Medicamentos , Feminino , Humanos , Contagem de Leucócitos , Leucopenia/induzido quimicamente , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Recidiva Local de Neoplasia , Trombocitopenia/induzido quimicamente , Vômito/induzido quimicamenteRESUMO
Twenty-nine patients with advanced or recurrent squamous cell carcinoma of the cervix who had failed standard therapy were treated with maytansine 1.2 mg/m2 intravenously once every 3 weeks. Only one partial remission was observed among the 29 patients (3%). There were no complete remissions. Stable disease was observed in 18 (62%) and progressive disease in 10 (35%). Adverse effects were infrequent and mild to moderate and consisted primarily of myelosuppression, weakness, and nausea and vomiting. This study shows that maytansine at the dose and schedule tested is essentially inactive in the treatment of advanced or recurrent squamous cell carcinoma of the cervix.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Maitansina/uso terapêutico , Oxazinas/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Avaliação de Medicamentos , Feminino , Humanos , Contagem de Leucócitos , Leucopenia/induzido quimicamente , Maitansina/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Trombocitopenia/induzido quimicamenteRESUMO
Twenty patients with advanced or recurrent leiomyosarcoma of the uterus who failed prior chemotherapy were placed on study by the Gynecologic Oncology Group. One patient had insufficient data to permit analysis. Of the remaining 19, there was only one objective response to cisplatin 50 mg/m2 intravenously every 3 weeks. Although toxicity was tolerable, there is little evidence of drug activity in patients with leiomyosarcomas of the uterus when the drug is given as second-line chemotherapy in the dose and schedule tested.