RESUMO
BACKGROUND: Paclitaxel-carboplatin is used as the standard regimen for patients with advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was designed to compare gemcitabine + carboplatin or gemcitabine + paclitaxel to the standard regimen. PATIENTS AND METHODS: A total of 1135 chemonaive patients with stage IIIB or IV NSCLC were randomly allocated to receive gemcitabine 1000 mg/m(2) on days 1 and 8 plus carboplatin area under the concentration-time curve (AUC) 5.5 on day 1 (GC), gemcitabine 1000 mg/m(2) on days 1 and 8 plus paclitaxel 200 mg/m(2) on day 1 (GP), or paclitaxel 225 mg/m(2) plus carboplatin AUC 6.0 on day 1 (PC). Stratification was based on disease stage, baseline weight loss, and presence or absence of brain metastases. Cycles were repeated every 21 days for up to six cycles or disease progression. RESULTS: Median survival (months) with GC was 7.9 compared with 8.5 for GP and 8.7 for PC. Response rates (RRs) were as follows: GC, 25.3%; GP, 32.1%; and PC, 29.8%. The GC arm was associated with a greater incidence of grade 3 or 4 hematologic events but a lower rate of neurotoxicity and alopecia when compared with GP and PC. CONCLUSIONS: Non-platinum and non-paclitaxel gemcitabine-containing doublets demonstrate similar overall survival and RR compared with the standard PC regimen. However, the treatment arms had distinct toxicity profiles.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
PURPOSE: Objectives of this study were to obtain data from Eastern Cooperative Oncology Group (ECOG) oncologists regarding their views on quality of life (QOL) information; perform psychometric testing on the MD-QOL questionnaire, develop a model to describe oncologists' willingness to use QOL information and propose data-based interventions to facilitate use of QOL information in clinical decision-making. METHODS: A self-administered questionnaire, MD-QOL, designed to assess physician perspective on QOL information was mailed to a random sample of 500 oncologists, members of ECOG; 271 responded. RESULTS: Oncologists' attitude, current behaviour, knowledge of QOL data, and reported willingness to use QOL can be measured using MD-QOL. The attitude, behaviour and willingness scales have high internal consistency. Physician attitude and behaviour account for 59% of the variance in the willingness to use QOL information. Demographic variables influencing physician responses were their primary income source and exposure to trials with a QOL component. CONCLUSIONS: This report of ECOG oncologists' views on QOL information suggests a model to describe relationship between physician willingness to use QOL information on the basis of their attitude and behaviour. Data-based interventions are proposed to influence the key variables and thus facilitate the incorporation of QOL data in clinical practice.
Assuntos
Atitude do Pessoal de Saúde , Oncologia , Qualidade de Vida , Inquéritos e Questionários , Análise de Variância , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
PURPOSE: Although several new chemotherapeutic agents are promising as primary therapy in non-small-cell lung cancer (NSCLC), few have demonstrated activity in platinum-refractory disease. Based on encouraging results reported in two single-institution studies of docetaxel in this setting, we performed a multicenter phase II trial evaluating this novel taxane in previously treated NSCLC patients prospectively categorized by platinum response status. PATIENTS AND METHODS: Eighty patients with NSCLC previously treated with platinum-based chemotherapy received docetaxel at a dose of 100 mg/m(2) intravenously over 1 hour, repeated every 21 days, accompanied by dexamethasone 8 mg orally twice daily for 5 days. Forty-seven patients (59%) were defined as platinum-refractory based on response status to prior therapy. RESULTS: The median number of cycles delivered per patient was four (range, one to 21 cycles). Partial response was observed in 13 (16%) of 80 of patients, with similar response rates in platinum-sensitive and platinum-refractory patients. The median survival time was 7 months, and the 1-year survival rate was 25%. Docetaxel was relatively well tolerated in this previously treated population. Grade IV neutropenia was common in patients (77%) but typically of brief duration. Febrile neutropenia was observed in 11 patients (14%), with no fatal infections. Severe fluid retention was rare (4% of patients). CONCLUSIONS: This multicenter phase II trial confirms antitumor activity and encouraging survival with docetaxel therapy in platinum-treated and platinum-refractory NSCLC. To validate these results, a phase III trial randomizing platinum-treated patients to docetaxel or best supportive care is underway.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Análise de SobrevidaRESUMO
PURPOSE: Minority accrual onto clinical trials is of significant interest to cooperative oncology study groups. The Eastern Cooperative Oncology Group (ECOG) conducted a study to identify barriers and solutions to African American accrual onto clinical trials. METHODS: We hypothesize that the National Medical Association (NMA) might provide insight into ways to increase minority participation and that ECOG might facilitate that participation. Four sites were selected in which NMA chapters existed and ECOG main institutions with less than half of the corresponding percentage of minorities in their communities entered trials for 1992. Fifteen workshops were conducted using discussions and open-ended, self-administered questionnaires. RESULTS: Seventy percent of NMA physicians cited mistrust of the research centers, fear of losing patients, and a lack of respect from ECOG institutions as the most important barriers to minority cancer patient referrals, compared with 30% for ECOG physicians. Sixty-nine percent of NMA and 43% of ECOG physicians cited a lack of information about specific trials. Nearly half of NMA physicians (47%) cited a lack of minority investigators as a barrier, compared with 4% of ECOG physicians. Solutions by both groups were improved communication (73%) and culturally relevant educational materials (40%). ECOG physicians cited more minority outreach staff as a potential solution (22% v 6%). NMA physicians cited increased involvement of referring physicians (44% v4%). CONCLUSION: NMA physicians who serve a significant sector of the African American population demonstrated a willingness to participate and work with a cooperative group effort to increase participation of minority patients and investigators.
Assuntos
Ensaios Clínicos como Assunto/métodos , Barreiras de Comunicação , Grupos Minoritários , Neoplasias/terapia , Coleta de Dados , Humanos , Papel do Médico , Projetos Piloto , Sociedades Médicas , Inquéritos e Questionários , Estados UnidosRESUMO
Oral etoposide has been tested alone and in combination in a number of tumour types since the late 1980s because of its mild toxicity, high response rates, ease of administration, and comparatively low cost. Encouraging early results with protracted oral etoposide therapy in small cell lung cancer have not been borne out in non-small cell lung cancer (NSCLC), particularly in the advanced-disease setting. However, in stage IV NSCLC, oral etoposide does appear to be as compatible with most of the newer agents as it has been with platinum compounds; these combinations continue to be explored, although they have not penetrated into standard usage. In stage III NSCLC, large combined-modality studies are ongoing. Other investigations examining protracted administration in combination with radiation 'sensitisers' are planned. It is possible that by exploiting the 'radiosensitising effect' of prolonged low dose oral etoposide, combined with that of other proven radiosensitisers such as paclitaxel, gemcitabine, and topotecan, we may identify a niche for oral etoposide in the future.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Etoposídeo/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Administração Oral , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , HumanosRESUMO
In recent years significant advances have been made in the treatment of metastatic non-small cell lung cancer. These advances have been due to both the discovery of new, more active drugs and an enhanced understanding of the biology of the disease, which has guided treatment decisions. Today, agents such as paclitaxel, docetaxel, vinorelbine, irinotecan, and gemcitabine are used in combinations that have demonstrated higher overall response rates and longer median overall survival durations than the previous generation of regimens based primarily on cisplatin, etoposide, and vinblastine. Of these new agents, paclitaxel has been the most widely studied and has demonstrated considerable activity when administered in a wide range of doses and schedules. Regimens with significant activity include paclitaxel and carboplatin as well as paclitaxel, carboplatin, and gemcitabine. However, because the optimal doses and schedules have not been clearly elucidated, current research efforts continue to focus on variations of these regimens. Just as advances have been made in the treatment of metastatic disease, it also has been clearly demonstrated that preoperative chemotherapy (+/- radiation) dramatically improves the overall survival for patients with stage III disease. The identification of growth factors, growth factor receptors, oncogenes, and tumor suppressor genes, which influence this disease, is providing new targets for future treatment strategies. Likewise, new therapeutic entities such as antiangiogenesis agents and matrix metalloproteinase inhibitors are being evaluated.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Humanos , Neoplasias Pulmonares/mortalidade , Receptor ErbB-2/análise , Taxa de SobrevidaRESUMO
BACKGROUND: The origins of and interrelations between low grade and high grade neuroendocrine lung tumors, typical and atypical carcinoids, and small cell lung carcinoma (SCLC) have not been elucidated. Karyotypic and molecular genetic studies have demonstrated deletions in 3p in 100% of SCLCs and the candidate lung tumor suppressor gene, FHIT, at 3p14.2 is not expressed in the majority of SCLCs. Similar studies of typical and atypical carcinoids could clarify the interrelations among these tumors. METHODS: For molecular genetic analyses, archival carcinoids and paired normal cells were microdissected from paraffin sections, deparaffinized, and DNA prepared. Oligonucleotide primer pairs for 12 microsatellite markers mapping between 3p14.2 and 3p21.3 were used to amplify allelic DNA fragments from 13 typical and 6 atypical carcinoids. In addition, an independent series of archival sections of carcinoids and SCLCs was tested by immunohistochemistry for expression of Fhit protein. RESULTS: Of the six atypical carcinoids examined, three had lost an allele at all informative markers, whereas one had lost alleles in two distinct regions and two showed allele loss in a subregion of the chromosome region tested. Of the 13 typical carcinoids, 3 showed allele loss at only 1 or 2 loci each. Typical carcinoids, similar to normal lung epithelia, were strongly positive for the cytoplasmic Fhit protein, SCLCs were uniformly negative, and atypical carcinoids appeared to express an intermediate level of Fhit protein. CONCLUSIONS: Loss of heterozygosity at 3p14.2-p21.3 is significantly more extensive in all atypical carcinoids. Atypical carcinoids, which exhibit clinicopathologic features intermediate between typical carcinoids and small cell carcinomas and have been considered well differentiated neuroendocrine carcinomas, also are intermediate between typical carcinoids and SCLC on the basis of extent of loss of 3p alleles and reduced expression of Fhit protein.
Assuntos
Hidrolases Anidrido Ácido , Tumor Carcinoide/genética , Carcinoma de Células Pequenas/genética , Cromossomos Humanos Par 3/genética , Perda de Heterozigosidade , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/análise , Proteínas/análise , Adulto , Idoso , Tumor Carcinoide/química , Carcinoma de Células Pequenas/química , Feminino , Humanos , Neoplasias Pulmonares/química , Masculino , Pessoa de Meia-IdadeRESUMO
The Cooperative Group system of the National Cancer Institute (NCI) has been in existence since the 1950s and has evolved to comprise 11 groups, the membership of which includes universities, Community Clinical Oncology Programs, and Cooperative Group Outreach Programs. The Cooperative Groups serve as models for cancer clinical trials throughout the world. However, in today's changing healthcare environment in the USA the Cooperative Groups need to adjust how they operate to ensure the continuation of their leadership role in cancer clinical trials. Government funds, the main source of support for the Cooperative Groups' activities, are shrinking and currently funding is only 50% of the recommended level. If the Cooperative Groups are to remain at the forefront, adjustments must be made in several areas: the Cooperative Groups need to provide an efficient and rapid scientific and legal mechanism to execute large phase III studies of the increasingly important portfolio of compounds being developed by industry more effectively. Industry has come to rely on contract research organizations for expedited testing of their products due to perceived inefficiency in these areas in the Cooperative Group mechanism. The Cooperative Groups are uniquely situated to provide in-depth evaluation of the newest therapies for regulatory agencies and interested health insurers, as well as provide health outcomes data, which are now much sought after by the healthcare industry. Managed care is shaping medical practice, including cancer care, throughout the USA. Finally, the Cooperative Groups need to foster greater international cooperation to speed technology transfers. The leaders of the Cooperative Groups are discussing new approaches to address these deficiencies, while complementing the existing NCI structure and recognizing the independence of each group. The objectives of these new approaches would be: to establish a structure whereby better contracts with industry for conducting trials can be established; to enhance international cooperation in clinical trials; to encourage greater involvement of third-party payers in clinical trials; to build on the scientific breadth of the members; to identify the most appropriate therapies to consider for reimbursement; to establish a framework which builds on the strengths of each of the members; and to integrate health outcomes and economic measures into the protocol activities. The Cooperative Groups are making changes to ensure they remain the leaders in cancer clinical trials well into the 21st century. The benefits of these adjustments will be realized not only by patients, but also by health professionals and the healthcare industry.
Assuntos
National Institutes of Health (U.S.)/organização & administração , Neoplasias/terapia , Humanos , Inovação Organizacional , Pesquisa/organização & administração , Pesquisa/tendências , Estados UnidosRESUMO
Despite advances in the treatment of small-cell lung cancer during the 1970s, with the use of combination chemotherapy, and in the 1980s, with the combination of etoposide and cisplatin plus concurrent radiation therapy, treatment success seems to have reached a plateau in the current decade. Research should now be directed into three areas: (1) strategies to prevent the development of second cancers, one of the major causes of death in people "cured" of their first primary cancer; (2) introduction of new agents such as paclitaxel (Taxol) and other newer chemotherapeutic drugs into clinical trials, particularly in conjunction with radiation therapy in limited disease; and (3) development of new therapeutic approaches, such as the modulation of drug resistance, molecular biology interventions, and monoclonal antibody therapy, strategies that are based on increased understanding of small-cell lung cancer biology. Although it is doubtful that any single strategy will be curative, selective approaches that exploit new research findings in conjunction with moderately effective, more conventional treatments might allow us to raise remission and survival rates significantly.
Assuntos
Carcinoma de Células Pequenas/terapia , Neoplasias Pulmonares/terapia , Adjuvantes Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Terapia Combinada , Previsões , Humanos , Imunotoxinas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Academic health centers (AHCs) and managed care organizations (MCOs) appear to be on a collision course. Is it possible to develop a partnership to enable both parties to achieve their respective goals and objectives? The Kimmel Cancer Center of Thomas Jefferson University and AEtna US Healthcare, one of the nation's largest MCOs, have developed an alliance designed to generate cancer prevention and control research. This arrangement engages the participants in a collaborative effort that is aimed at creating new knowledge that can be used to enhance the provision of health care to a defined population.
Assuntos
Centros Médicos Acadêmicos/organização & administração , Institutos de Câncer/organização & administração , Programas de Assistência Gerenciada/organização & administração , Neoplasias/prevenção & controle , Afiliação Institucional , Apoio à Pesquisa como Assunto/organização & administração , Comportamento Cooperativo , Humanos , Objetivos Organizacionais , Assistência ao Paciente , PhiladelphiaRESUMO
PURPOSE: To examine the effect of treatment using Bromodeoxyuridine (BrdU) during radiation therapy on malignant glioma patient survival by comparing historical survival data from several large clinical trials. METHODS: A retrospective analysis of patient data from Radiation Therapy Oncology Group (RTOG) trials 74-01, 79-18, and 83-02 and the Northern California Oncology Group (NCOG) study 6G-82-1 was conducted. Patient data was supplied by both groups, and analyzed by the RTOG. Pretreatment characteristics including age, extent of surgery, Karnofsky Performance Status (KPS), and histopathology were collected; the only treatment variable evaluated was the use of BrdU during radiation therapy. Radiation dose, dose-fractionation schedule, use of chemotherapy, and/or type of chemotherapy was not controlled for in the analyses. Univariate and multivariate analyses were conducted to examine the potential treatment effect of BrdU on patient survival. RESULTS: Data from 334 patients treated with BrdU on NCOG 6G-82-1 and 1743 patients treated without BrdU on 3 RTOG studies was received. Patients were excluded from the review if confirmation of eligibility could not be obtained, if the patient was ineligible for the study they entered, if central pathology review was not done, or if radiotherapy data was not available. Patients treated according to the RTOG studies had to start radiotherapy within 4 weeks of surgery; no such restriction existed for the NCOG studies. To ensure comparability between the studies, patients from the NCOG studies who began treatment longer than 40 days from surgery were also excluded. The final data set included 296 cases from the NCOG studies (89%) and 1478 cases from the RTOG studies (85%). For patients with glioblastoma multiforme (GBM) the median survival was 9.8 months in the RTOG studies and 13.0 months in the NCOG trial (p < 0.0001). For patients with AA the median survival was 35.1 months for the RTOG studies and 42.8 months in the NCOG trial (p = 0.126). Univariate results showed consistent results favoring BrdU among patients over 30 years of age, across the extent of surgery, and for GBM patients. A proportional hazards regression model that included treatment, histopathology, KPS, age, and extent of surgery demonstrated that treatment with BrdU was included in the best model only for the GBM group of patients (risk ratio 0.83). CONCLUSIONS: Because of the heterogeneity of the treatment groups, including potentially important differences in pathology reviewers assessment of nonglioblastoma cases, differences in radiation dose and schedules, and chemotherapy during or after radiation, these analyses cannot provide the definitive answer as to whether BrdU given during radiation therapy improves survival in patients with malignant glioma. There does appear to be a favorable treatment effect seen in patients with GBM, with a lesser effect in patients with AA.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Bromodesoxiuridina/uso terapêutico , Glioma/mortalidade , Glioma/radioterapia , Radiossensibilizantes/uso terapêutico , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Astrocitoma/tratamento farmacológico , Astrocitoma/mortalidade , Astrocitoma/radioterapia , Neoplasias Encefálicas/tratamento farmacológico , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/mortalidade , Glioblastoma/radioterapia , Glioma/tratamento farmacológico , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos RetrospectivosRESUMO
BACKGROUND: This study is a retrospective analysis of data collected from patient medical records, a fecal occult blood test (FOBT) screening program, and computerized health maintenance organization (HMO) claims and encounters records. OBJECTIVE: To identify factors associated with a diagnosis of early (Dukes A and B) colorectal cancer among older adults targeted for annual FOBT screening. METHODS: Study subjects were insured by the former US Healthcare Inc (Blue Bell, Pa), an independent practice association-type HMO. The HMO was recently integrated into Aetna-US Healthcare. Before diagnosis, subjects were eligible for free annual FOBT screening through the HMO's colorectal cancer screening program. The study subjects included men and women (N = 222) who were aged 50 years or older and had a diagnosis of colorectal cancer between 1987 and 1990. Variables considered were patient age, gender, socioeconomic status, medical history, screening history, length of enrollment in the HMO, and stage of disease at diagnosis. RESULTS: Univariate analyses indicate that colorectal cancer diagnosis due to FOBT screening (P = .03), frequency of FOBT screening (P = .09), and length of HMO membership (P = .10) were positively related to being diagnosed as having early stage colorectal cancer. Multivariable analysis shows that having a screen-detected colorectal cancer was significantly and positively related (P = .03) to being diagnosed as having early stage disease. CONCLUSIONS: Findings support annual FOBT screening among older adults. Results illustrate the value of applying standard methods to the collection and analysis of patient data in a managed care context. The study also highlights a need for research on patient adherence to screening and physician follow-up of abnormal screening test results.
Assuntos
Neoplasias Colorretais/patologia , Sistemas Pré-Pagos de Saúde/organização & administração , Programas de Rastreamento/organização & administração , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Neoplasias Colorretais/prevenção & controle , Feminino , Sistemas Pré-Pagos de Saúde/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , New Jersey , Sangue Oculto , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pennsylvania , Estudos Retrospectivos , Fatores SocioeconômicosAssuntos
Carcinoma de Células Pequenas/terapia , Neoplasias Pulmonares/terapia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Carcinoma de Células Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Sociedades MédicasRESUMO
Telemedicine is being used by physicians at the member hospitals of the Jefferson Cancer Network (JCN) for consultations regarding the diagnosis and management of cancer patients. The technology employed for this telemedicine system was chosen to meet three related specifications: low capital and operating cost, internal maintainability by community hospital data processing staffs, and compatibility with the existing technologic infrastructure. The solution selected is the ubiquitous desktop personal computer and associated software, and Integrated Services Digital Network (ISDN) communications links. The overall performance of this technology has been very satisfactory; ISDN communications has sufficient bandwidth for the transfer of patient data, including text reports, radiographs, and pathology slide images. The presence of the radiologist's interpretation along with the radiographic images allows the presentation of the images on these systems to be acceptable for review purposes. The video frame rates of these systems (12 to 15 frames per second) is adequate, particularly given the "talking heads" nature of the video presentations. Furthermore, the quality of the video image (resolution, size, frame rate) is secondary to the quality of the presentation of the medical information displayed and the capability for mutual annotation of the patient data during the consultation.
Assuntos
Redes Comunitárias/organização & administração , Redes de Comunicação de Computadores , Neoplasias , Telemedicina/organização & administração , Ensaios Clínicos como Assunto , Redes de Comunicação de Computadores/economia , Redes de Comunicação de Computadores/estatística & dados numéricos , Difusão de Inovações , Hospitais Comunitários/organização & administração , Hospitais de Ensino/organização & administração , Humanos , Serviços de Informação , Microcomputadores , Neoplasias/diagnóstico , Neoplasias/terapia , Seleção de Pacientes , Philadelphia , Integração de Sistemas , Telemedicina/estatística & dados numéricosRESUMO
OBJECTIVES: To review the current status and recent advances, and ongoing research efforts related to the diagnosis, staging, and treatment of small cell lung cancer (SCLC). DATA SOURCES: Review articles, book chapters, research studies, and abstracts relating to SCLC. CONCLUSIONS: SCLC is the most aggressive type of lung cancer with many patients having widespread disease at the time of diagnosis. It is the most treatment responsive lung cancer to both chemotherapy and radiotherapy, with aggressive chemotherapy the cornerstone of treatment. Yet, the survival rate is limited. Several new drugs have been found to be active and it is hoped that they will lead to improved results. IMPLICATIONS FOR NURSING PRACTICE: An understanding of the prognostic factors, staging, treatment modalities, and new therapies for SCLC will help nurses assist patients to make educated decisions about the potential risks and benefits of their therapeutic options.
Assuntos
Carcinoma de Células Pequenas , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/etiologia , Carcinoma de Células Pequenas/terapia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/terapia , Estadiamento de Neoplasias , Enfermagem Oncológica , Educação de Pacientes como Assunto , Prognóstico , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Patients with locally advanced, initially unresectable non-small cell lung cancer (NSCLC) have a median survival time of 9 to 11 months, a 2-year survival rate of 13%, and a long-term survival rate of 5% to 7% when treated with radical thoracic radiation alone. Because of the preclinical radiosensitizing capabilities of 5-fluorouracil and cisplatin and the therapeutic synergy of etoposide and cisplatin, we combined these agents with full-dose radical thoracic radiation to determine the feasibility and efficacy of this approach in locally advanced NSCLC. METHODS: Patients with clinical stage IIIb and bulky IIIa NSCLC and ECOG performance status 0 or 1 received 5-fluorouracil infusion (640-800 mg/m2/d CVI days 1-5, 29-34), cisplatin (20 mg/m2/d, days 1-5, 29-34), etoposide (50 mg/m2, days 1, 3, 5, 29, 31, 33) and concurrent thoracic radiation (60 Gy/2 Gy/d/30 Fx). Patients with adequate cytoreduction proceeded to surgical resection. RESULTS: From March 1987 to July 1990, 41 patients were enrolled on study; 40 are evaluable. The objective response rate was 90%. Thirteen patients (39%), five with clinical stage IIIb disease and eight with IIIa disease, underwent thoracotomy and resection; three proved to have pathological complete remissions. Ten of 77 chemotherapy courses were complicated by neutropenic fever. Grade 3 or 4 esophagitis occurred in 21 patients (52%). Cardiac ischemia or infarction occurred in two patients (5%). There were seven deaths in the first 6 months in the absence of disease progression. Two-year survival was 38%, 3-year survival 25%, and 4- to 5-year survival 18%. Six patients (15%) remain alive at the median follow-up time of 66 months (range, 64-84). CONCLUSIONS: Despite substantial early morbidity and mortality, concurrent, aggressive chemoradiation produced a long-term survival rate in locally advanced NSCLC comparable to other combined modality approaches. However toxicity, particularly esophagitis and postoperative complications, preclude the use of this regimen in phase III studies. Combined modality approaches for locally advanced, initially unresectable NSCLC have become standard; research must simultaneously focus on ways to enhance efficacy and reduce toxicity.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Tratamento Farmacológico , Feminino , Humanos , Masculino , Procedimentos Cirúrgicos Pulmonares , Radioterapia Adjuvante , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE AND METHODS: Resistance to alkylating agents and platinum compounds is associated with elevated levels of glutathione (GSH). Depletion of GSH by buthionine sulfoximine (BSO) restores the sensitivity of resistant tumors to melphalan in vitro and in vivo. In a phase I trial, each patient received two cycles as follows: BSO alone intravenously (i.v.) every 12 hours for six doses, and 1 week later the same BSO as cycle one with melphalan (L-PAM) 15 mg/m2 i.v. 1 hour after the fifth dose. BSO doses were escalated from 1.5 to 17 g/m2 in 41 patients. RESULTS: The only toxicity attributable to BSO was grade I or II nausea/vomiting in 50% of patients. Dose-related neutropenia required an L-PAM dose reduction to 10 mg/m2 at BSO 7.5 g/m2. We measured GSH in peripheral mononuclear cells (PMN), and in tumor biopsies when available, at intervals following BSO dosing. In PMNs, GSH content decreased over 36 to 72 hours to reach a nadir on day 3; at the highest dose, recovery was delayed beyond day 7. The mean PMN GSH nadirs were approximately 10% of control at BSO doses > or = 7.5 g/m2; at 13 and 17 g/m2, all but two patients had nadir values in this range. GSH was depleted in sequential tumor biopsies to a variable extent, but with a similar time course. At BSO doses > or = 13 g/m2, tumor GSH was < or = 20% of starting values on day 3 in five of seven patients; recovery had not occurred by day 5. We measured plasma concentrations of R- and S-BSO by high-performance liquid chromatography (HPLC) in 22 patients throughout the dosing period. Total-body clearance (CLt) and volume of distribution at steady-state (Vss) for both isomers were dose-independent. The CLt of S-BSO was significantly less than that of R-BSO at all doses, but no significant differences in Vss were observed between the racemates. Harmonic mean half-lives were 1.39 hours and 1.89 hours for R-BSO and S-BSO, respectively. CONCLUSION: A biochemically appropriate dose of BSO for use on this schedule is 13 g/m2, which will be used in phase II trials to be conducted in ovarian cancer and melanoma.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Metionina Sulfoximina/análogos & derivados , Neoplasias/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/toxicidade , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Medula Óssea/efeitos dos fármacos , Butionina Sulfoximina , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Feminino , Glutationa/sangue , Glutationa/efeitos dos fármacos , Humanos , Modelos Lineares , Masculino , Melfalan/administração & dosagem , Metionina Sulfoximina/administração & dosagem , Metionina Sulfoximina/farmacocinética , Metionina Sulfoximina/toxicidade , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Neutropenia/induzido quimicamente , Neutrófilos/efeitos dos fármacos , Radiografia , Vômito/induzido quimicamenteRESUMO
Human papillomavirus (HPV) is associated with 65-95% of in situ or early invasive squamous cell carcinomas of the cervix. A multiinstitutional, prospective phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) to study the activity of IFN-alpha 2b in women with metastatic or locally recurrent cervix cancer. The activity of IFN-alpha 2b was correlated with the presence of HPV as measured by Southern blot hybridization or polymerase chain reaction techniques in 17 patients. All patients had failed prior definitive therapy with surgery, radiation, and chemotherapy. IFN-alpha 2b was administered at 10 MU/m2 subcutaneously three times per week. Among 31 patients enrolled, 3 achieved a clinical response to treatment. Tumor was accessible for biopsy in 17 patients. The presence of HPV was assayed by Southern blot hybridization (2 of 17) and/or polymerase chain reaction (PCR) technology (15 of 17). Of the 17 assays, 16 were informative. HPV was detected in 5 of 16 patients. Of 5 HPV-positive women, 2 responded to treatment, versus 1 of 11 HPV-negative women, thus not permitting reliable statistical analysis. It is concluded that IFN-alpha 2b has only minimal activity against advanced, recurrent cervical cancer.