RESUMO
BACKGROUND: On Aug 14, 2014, the US Food and Drug Administration approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer on the basis of improved overall survival (OS) after the second interim analysis (in 2012) of 271 deaths in the Gynecologic Oncology Group (GOG) 240 trial. In this study, we report the prespecified final analysis of the primary objectives, OS and adverse events. METHODS: In this randomised, controlled, open-label, phase 3 trial, we recruited patients with metastatic, persistent, or recurrent cervical carcinoma from 81 centres in the USA, Canada, and Spain. Inclusion criteria included a GOG performance status score of 0 or 1; adequate renal, hepatic, and bone marrow function; adequately anticoagulated thromboembolism; a urine protein to creatinine ratio of less than 1; and measurable disease. Patients who had received chemotherapy for recurrence and those with non-healing wounds or active bleeding conditions were ineligible. We randomly allocated patients 1:1:1:1 (blocking used; block size of four) to intravenous chemotherapy of either cisplatin (50 mg/m2 on day 1 or 2) plus paclitaxel (135 mg/m2 or 175 mg/m2 on day 1) or topotecan (0·75 mg/m2 on days 1-3) plus paclitaxel (175 mg/m2 on day 1) with or without intravenous bevacizumab (15 mg/kg on day 1) in 21 day cycles until disease progression, unacceptable toxic effects, voluntary withdrawal by the patient, or complete response. We stratified randomisation by GOG performance status (0 vs 1), previous radiosensitising platinum-based chemotherapy, and disease status (recurrent or persistent vs metastatic). We gave treatment open label. Primary outcomes were OS (analysed in the intention-to-treat population) and adverse events (analysed in all patients who received treatment and submitted adverse event information), assessed at the second interim and final analysis by the masked Data and Safety Monitoring Board. The cutoff for final analysis was 450 patients with 346 deaths. This trial is registered with ClinicalTrials.gov, number NCT00803062. FINDINGS: Between April 6, 2009, and Jan 3, 2012, we enrolled 452 patients (225 [50%] in the two chemotherapy-alone groups and 227 [50%] in the two chemotherapy plus bevacizumab groups). By March 7, 2014, 348 deaths had occurred, meeting the prespecified cutoff for final analysis. The chemotherapy plus bevacizumab groups continued to show significant improvement in OS compared with the chemotherapy-alone groups: 16·8 months in the chemotherapy plus bevacizumab groups versus 13·3 months in the chemotherapy-alone groups (hazard ratio 0·77 [95% CI 0·62-0·95]; p=0·007). Final OS among patients not receiving previous pelvic radiotherapy was 24·5 months versus 16·8 months (0·64 [0·37-1·10]; p=0·11). Postprogression OS was not significantly different between the chemotherapy plus bevacizumab groups (8·4 months) and chemotherapy-alone groups (7·1 months; 0·83 [0·66-1·05]; p=0·06). Fistula (any grade) occurred in 32 (15%) of 220 patients in the chemotherapy plus bevacizumab groups (all previously irradiated) versus three (1%) of 220 in the chemotherapy-alone groups (all previously irradiated). Grade 3 fistula developed in 13 (6%) versus one (<1%). No fistulas resulted in surgical emergencies, sepsis, or death. INTERPRETATION: The benefit conferred by incorporation of bevacizumab is sustained with extended follow-up as evidenced by the overall survival curves remaining separated. After progression while receiving bevacizumab, we did not observe a negative rebound effect (ie, shorter survival after bevacizumab is stopped than after chemotherapy alone is stopped). These findings represent proof-of-concept of the efficacy and tolerability of antiangiogenesis therapy in advanced cervical cancer. FUNDING: National Cancer Institute.
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Bevacizumab/efeitos adversos , Bevacizumab/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/mortalidade , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Topotecan/administração & dosagem , Topotecan/efeitos adversosRESUMO
PURPOSE: We examined disparities in prognosis between patients with ovarian clear cell carcinoma (OCCC) and serous epithelial ovarian cancer (SOC). METHODS: We reviewed data from FIGO stage I-IV epithelial ovarian cancer patients who participated in 12 prospective randomized GOG protocols. Proportional hazards models were used to compare progression-free survival (PFS) and overall survival (OS) by cell type (clear cell versus serous). RESULTS: There were 10,803 patients enrolled, 9531 were eligible, evaluable and treated with platinum, of whom 544 (6%) had OCCC, 7054 (74%) had SOC, and 1933 (20%) had other histologies and are not included further. In early stage (I-II) patients, PFS was significantly better in OCCC than in SOC patients. For late stage (III, IV) patients, OCCC had worse PFS and OS compared to SOC, OS HR=1.66 (1.43, 1.91; p<0.001). After adjusting for age and stratifying by protocol and treatment arm, stage, performance status, and race, OCCC had a significantly decreased OS, HR=1.53 (1.33, 1.76; p<0.001). In early stage cases, there was a significantly decreased treatment effect on PFS for consolidative therapy with weekly Paclitaxel versus observation in OCCC compared to SOC (p=0.048). CONCLUSIONS: This is one of the largest analyses to date of OCCC treated on multiple cooperative group trials. OCCC histology is more common than SOC in early stage disease. When adjusted for prognostic factors, in early stage patients, PFS was better for OCCC than for SOC; however, in late-stage patients, OCCC was significantly associated with decreased OS. Finally, treatment effect was influenced by histology.
Assuntos
Adenocarcinoma de Células Claras/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Carboplatina/administração & dosagem , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Prognóstico , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de SobrevidaRESUMO
PURPOSE: GOG 152 was a randomized trial of secondary cytoreductive surgery (SCS) in patients with suboptimal residual disease (residual tumor nodule >1cm in greatest diameter) following primary cytoreductive surgery for advanced stage ovarian cancer. The current analysis was undertaken to evaluate the impact of disease findings at SCS on progression-free survival (PFS) and overall survival (OS). METHODS: Among the 550 patients enrolled on GOG-152, two-hundred-sixteen patients were randomly assigned following 3cycles of cisplatin and paclitaxel to receive SCS. In 15 patients (7%) surgery was declined or contraindicated. In the remaining 201 patients the operative and pathology reports were utilized to classify their disease status at the beginning of SCS as; no gross disease/microscopically negative N=40 (19.9%), no gross disease/microscopically positive N=8 (4.0%), and gross disease N=153 (76.1%). RESULTS: The median PFS for patients with no gross disease/microscopically negative was 16.1months, no gross disease/microscopically positive was 13.5months and for gross disease was 11.7months, P=0.002. The median OS for patients with no gross disease/microscopically negative was 51.5months, no gross disease/microscopically positive was 42.6months and for gross disease was 34.9months, P=0.018. CONCLUSION: Although as previously reported SCS did not change PFS or OS, for those who underwent the procedure, their operative and pathologic findings were predictive of PFS and OS. Surgical/pathological residual disease is a biomarker of response to chemotherapy and predictive of PFS and OS.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Endometrioide/patologia , Procedimentos Cirúrgicos de Citorredução , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Ovarianas/patologia , Reoperação , Idoso , Carcinoma Endometrioide/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias Císticas, Mucinosas e Serosas/cirurgia , Neoplasias Ovarianas/cirurgia , Paclitaxel/administração & dosagem , Prognóstico , Taxa de SobrevidaRESUMO
OBJECTIVE: To determine the effect of age on completion of and toxicities following treatment of local regionally advanced cervical cancer (LACC) on Gynecologic Oncology Group (GOG) Phase I-III trials. METHODS: An ancillary data analysis of GOG protocols 113, 120, 165, 219 data was performed. Wilcoxon, Pearson, and Kruskal-Wallis tests were used for univariate and multivariate analysis. Log rank tests were used to compare survival lengths. RESULTS: One-thousand-three-hundred-nineteen women were included; 60.7% were Caucasian, 15% were age 60-70years and an additional 5% were >70; 87% had squamous histology, 55% had stage IIB disease and 34% had IIIB disease. Performance status declined with age (p=0.006). Histology and tumor stage did not significantly differ. Number of cycles of chemotherapy received, radiation treatment time, nor dose modifications varied with age. Notably, radiation protocol deviations and failure to complete brachytherapy (BT) did increase with age (p=0.022 and p<0.001 respectively). Only all grade lymphatic (p=0.006) and grade≥3 cardiovascular toxicities (p=0.019) were found to vary with age. A 2% increase in the risk of death for every year increase >50 for all-cause mortality (HR 1.02; 95% CI, 1.01-1.04) was found, but no association between age and disease specific mortality was found. CONCLUSION: This represents a large analysis of patients treated for LACC with chemo/radiation, approximately 20% of whom were >60years of age. Older patients, had higher rates of incomplete brachytherapy which is not explained by collected toxicity data. Age did not adversely impact completion of chemotherapy and radiation or toxicities.
Assuntos
Quimiorradioterapia , Neoplasias do Colo do Útero/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Braquiterapia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Neoplasias do Colo do Útero/mortalidadeRESUMO
OBJECTIVE: Conflicting results have been reported for adeno- and adenosquamous carcinomas of the cervix with respect to their response to therapy and prognosis. The current study sought to evaluate impact of adeno- and adenosquamous histology in the randomized trials of primary cisplatin-based chemoradiation for locally advanced cervical cancer. METHODS: Patients with adeno- and adenosquamous cervical carcinomas were retrospectively studied and compared to squamous cell carcinomas in GOG trials of chemoradiation. RESULTS: Among 1671 enrolled in clinical trials of chemoradiation, 182 adeno- and adenosquamous carcinomas were identified (10.9%). A higher percentage of adeno- and adenosquamous carcinomas were stage IB2 (27.5% versus 20.0%) and fewer had stage IIIB (21.4% versus 28.6%). The mean tumor size was larger for squamous than adeno- and adenosquamous. Adeno- and adenosquamous carcinomas were more often poorly differentiated (46.2% versus 26.8%). When treated with radiation therapy alone, the 70 patients with adeno- and adenosquamous carcinoma of the cervix showed a statistically poorer overall survival (p=0.0499) compared to the 647 patients with squamous cell carcinoma of the cervix. However, when treated with radiation therapy with concurrent cisplatin-based chemotherapy, the 112 patients with adeno- and adenosquamous carcinomas had a similar overall survival (p=0.459) compared the 842 patients with squamous cell carcinoma. Adverse effects to treatment were similar across histologies. CONCLUSION: Adeno- and adenosquamous carcinomas of the cervix are associated with worse overall survival when treated with radiation alone but with similar progression-free and overall survival compared to squamous cell carcinomas of the cervix when treated with cisplatin based chemoradiation.
Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Adenoescamoso/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias do Colo do Útero/terapia , Adenocarcinoma/patologia , Adulto , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Eritropoetina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Hidroxiureia/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia/métodos , Proteínas Recombinantes/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral , Neoplasias do Colo do Útero/patologiaRESUMO
Ascites in epithelial ovarian cancer (EOC) promotes tumor development by mechanisms that are incompletely understood. Lysophosphatidic acid (LPA), a major tumor-promoting factor in EOC ascites, is an enzymatic product of autotaxin (ATX) and phospholipase A(2) (PLA(2))enzymes. The contribution of PLA(2) activities to ovarian tumorigenesis was investigated. The quantitative measurement of PLA(2) activities in ascites and tissues, as well as assay conditions selective for PLA(2) subtypes, were optimized and validated. PLA(2) activities correlated with tumor-promoting activates in cell-based and in vivo assays. High activities consistent with both cytosolic and calcium-independent PLA(2) were found in human EOC ascites for the first time. Elevated PLA(2) and ATX activities were also observed in EOC compared to benign tumors and normal tissues. Cell-free and vesicle-free (S4) human EOC ascites potently promoted proliferation, migration, and invasion of human EOC cells in a PLA(2)-dependent manner. LPA mediated a significant part of the cell-stimulating effects of ascites. S4 ascites stimulated tumorigenesis/metastasis in vivo, and methyl arachidonyl fluorophosphonate was highly effective in inhibiting EOC metastasis in mouse xenograft models. PLA(2) activity was found in conditioned media from both EOC cells and macrophages. Collectively, our work implies that PLA(2) activity is a potential marker and therapeutic target in EOC.
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Neoplasias Epiteliais e Glandulares/fisiopatologia , Neoplasias Ovarianas/fisiopatologia , Animais , Ácidos Araquidônicos/uso terapêutico , Ascite/patologia , Ascite/fisiopatologia , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Feminino , Humanos , Lisofosfolipídeos , Camundongos , Transplante de Neoplasias , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/patologia , Organofosfonatos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Fosfolipases A2 Secretórias , Diester Fosfórico Hidrolases/metabolismo , Transplante HeterólogoRESUMO
BACKGROUND: The Gynecologic Oncology Group (GOG) is a multi-institution cooperative group funded by the National Cancer Institute to conduct clinical trials encompassing clinical and basic scientific research in gynecologic malignancies. These results are disseminated via publication in peer-reviewed journals. This process requires collaboration of numerous investigators located in diverse cancer research centers. Coordination of manuscript development is positioned within the Statistical and Data Center (SDC), thus allowing the SDC personnel to manage the process and refine strategies to promote earlier dissemination of results. A major initiative to improve timeliness utilizing the assignment, monitoring, and enforcement of deadlines for each phase of manuscript development is the focus of this investigation. PURPOSE: Document improvement in timeliness via comparison of deadline compliance and time to journal submission due to expanded administrative and technologic initiatives implemented in 2006. METHODS: Major steps in the publication process include generation of first draft by the First Author and submission to SDC, Co-author review, editorial review by Publications Subcommittee, response to journal critique, and revision. Associated with each step are responsibilities of First Author to write or revise, collaborating Biostatistician to perform analysis and interpretation, and assigned SDC Clinical Trials Editorial Associate to format/revise according to journal requirements. Upon the initiation of each step, a deadline for completion is assigned. In order to improve efficiency, a publications database was developed to track potential steps in manuscript development that enables the SDC Director of Administration and the Publications Subcommittee Chair to assign, monitor, and enforce deadlines. They, in turn, report progress to Group Leadership through the Operations Committee. The success of the strategies utilized to improve the GOG publication process was assessed by comparing the timeliness of each potential step in the development of primary Phase II manuscripts during 2003-2006 versus 2007-2010. RESULTS: Improvement was noted in 10 of 11 identified steps resulting in a cumulative average improvement of 240 days from notification of data maturity to First Author through first submission to a journal. Moreover, the average time to journal acceptance has improved by an average of 346 days. LIMITATIONS: The investigation is based on only Phase II trials to ensure comparability of manuscript complexity. Nonetheless, the procedures employed are applicable to the development of any clinical trials manuscript. CONCLUSIONS: The assignment, monitoring, and enforcement of deadlines for all stages of manuscript development have resulted in increased efficiency and timeliness. The positioning and support of manuscript development within the SDC provide a valuable resource to authors in meeting assigned deadlines, accomplishing peer review, and complying with journal requirements.
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Políticas Editoriais , Neoplasias dos Genitais Femininos , Ginecologia , Editoração , Comportamento Cooperativo , Feminino , Humanos , Fatores de Tempo , Estados UnidosRESUMO
BACKGROUND: Granulocyte colony stimulating factor (G-CSF) and erythropoietin stimulating agents (ESA) may be used to support patients during chemotherapy. We assessed whether G-CSF or ESA were associated with progression or death in patients with ovarian cancer. METHODS: Patients with ovarian cancer following surgery, were on a protocol to evaluate bevacizumab with chemotherapy. Guidelines for administering G-CSF and ESA were specified in the protocol. Overall survival (OS) was analyzed with landmark procedures and multivariate, time-dependent hazard models. RESULTS: Eighteen-hundred-seventy-three women were enrolled, with no differences in clinical and pathologic variables among treatment group. Performance status, hemoglobin, and white cell counts were associated with G-CSF and/or ESA usage during treatment. Nine patients received no protocol directed therapy, leaving 1864 patients for this review. One-thousand-one-hundred-twenty-five patients received neither ESA nor G-CSF; 311 received G-CSF but no ESA; 241 received ESA but no G-CSF; and 187 received both. Median survival following a five month landmark from the start of treatment was 34 versus 38 months for those who did versus did not receive ESA (multivariate hazard ratio: 0.989; 95% confidence interval: 0.849-1.15) and 40 versus 37 months for those who did versus did not receive G-CSF (multivariate hazard ratio: 0.932; 95% confidence interval: 0.800-1.08). CONCLUSIONS: Neither ESA nor G-CSF had a negative impact on survival after adjustment of prognostic factors among patients with ovarian cancer receiving chemotherapy. ESA may appear to be associated with shorter survival in univariate analyses because factors prognostic for ESA use are also prognostic for progression-free survival.
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Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Hematínicos/efeitos adversos , Neoplasias Ovarianas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , PrognósticoRESUMO
OBJECTIVES: There is a lack of knowledge about the health care events experienced by individual patients that lead to a definitive diagnosis of ovarian cancer (OC). The goal of this study was to describe the various pathways and to identify an optimal path to accurate diagnosis. METHODS: Women who were referred to gynecologic oncology for a suspected OC were enrolled to this study. Medical records (MRs) from all health care providers were obtained from the time the patient recalled first suspecting a health issue through the time of diagnosis to build a decision tree model. A Monte Carlo simulation was conducted of 83,000 patients to identify the optimal pathway to reach diagnosis. RESULTS: In the Monte Carlo simulation, gynecologic oncologists and gynecologists accounted for the most efficient diagnosis in over 37.9% and 29.2% of suspected OC cases, respectively, in terms of the least amount of time to reach diagnosis. Gynecologic oncologists were further associated with the fewest health care visits needed to reach diagnosis in 37% of the simulation cases; however, 23% of trials were indifferent to any specific provider. CONCLUSIONS: The decision tree provides a more comprehensive view of the complexity in reaching an accurate diagnosis of OC. This analysis was able to identify the health care utilization patterns that underlie the events that occur to reach an accurate diagnosis in the setting of a suspected OC, and was able to identify the most efficient pathways that utilize the fewest health care resources in the least amount of time.
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Detecção Precoce de Câncer , Neoplasias Ovarianas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Ca-125/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Método de Monte CarloRESUMO
INTRODUCTION: Health-related quality of life (HRQOL) has become an increasingly important focus of outcomes in cancer care with the movement toward more patient-oriented research. Quality-of-life outcomes are important in ovarian cancer, which has not yet benefitted from improved survival outcomes as have other diseases. This study was designed to systematically assess and summarize HRQOL in ovarian cancer. METHODS: A systematic search strategy was initiated to identify published literature measuring HRQOL of women with a diagnosis of ovarian cancer (OC). Data were synthesized to evaluate HRQOL and patient-reported outcome data at various time points: before, during, and after chemotherapy. Data were pooled and summary statistics compared across published studies. Comparisons of means were conducted using analysis of variance. RESULTS: There were 170 publications meeting all eligibility criteria, representing 139 unique studies of patients with ovarian cancer, where QOL data were collected. Within this literature, more than 90 different patient-reported outcome (PRO) instruments were administered. The most common HRQOL instruments included the European Organisation for Research and Treatment of Cancer QLQ-C30 and the Functional Assessment of Cancer Therapy. Few studies alone demonstrated significant differences in QOL between the experimental and comparison arm or throughout the treatment period. Pooled data, however, show that baseline QOL may significantly improve, particularly after completion of chemotherapy treatment. DISCUSSION: Despite the increase in assessment and reporting of QOL in ovarian cancer research studies during the past 15 years, there remains little consistency in the types and format of data collected. There is a need to enhance the standardized collection and reporting of HRQOL data from research involving women with ovarian cancer so that research can build on the cumulative knowledge base to improve outcomes in this patient population.
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Pesquisa Biomédica , Nível de Saúde , Neoplasias Ovarianas/terapia , Qualidade de Vida , Feminino , HumanosRESUMO
OBJECTIVES: To evaluate the outcome of stage IVA cervical cancer treated with radiation and concurrent cisplatin-based chemotherapy. METHODS: We conducted a retrospective study of stage IVA cervical cancer patients from four trials (Gynecologic Oncology Group protocols 56, 85, 120, and 165) treated with radiotherapy with or without concurrent cisplatin-based chemotherapy. Patient records were reviewed for demographic and tumor features, treatment, and progression-free survival (PFS) and overall survival (OS). Stage IVA patients were compared to stage IIIB patients from these same studies. RESULTS: Among the 51 stage IVA patients studied, 92% were stage IVA on the basis of bladder involvement. The median PFS was 10.1 months (95% CI=6.3-14.5 months) and median OS was 21.2 months (95% CI=13.3-30.5 months). The 3 year survival was 32%. On univariate analysis, only advanced age was associated with OS (p=0.0115) but age had only marginal effect on PFS (p=0.083). Pathologic proven pelvic nodal metastasis was of marginal significance for both PFS and OS, p=0.059 and 0.064, respectively. Despite similar patient characteristics, the use of cisplatin-based chemotherapy had no impact on PFS or OS but was underpowered to address this question. When compared to stage IIIB patients, stage IVA patients had a poorer performance status (p=0.0231), larger tumor size (p=0.0302), and more frequent bilateral parametrial involvement (0.0063). CONCLUSION: Patients with stage IVA disease had poor median survival of only 21 months with only 32% 3 year survival. Stage IVA patients have larger tumor size, more bilateral parametrial involvement, and poorer survival when compared to stage IIIB patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Idoso , Braquiterapia , Cisplatino/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Hidroxiureia/administração & dosagem , Pessoa de Meia-Idade , Misonidazol/administração & dosagem , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/patologiaRESUMO
There is now a greater understanding of the molecular pathways in ovarian cancer, and using this knowledge, a large number of new therapeutic agents can be tested. The success of these drugs will depend on selecting drugs that target known key dysfunctional molecular pathways. To make best use of these compounds, prognostic and predictive biomarkers need to be identified. Novel methods of assessment such as functional imaging need to be developed as additional biological end points to evaluate these therapies. Promising antitumor activity has been observed with some drugs, and careful consideration is needed to determine in what circumstances new agents, such as antiangiogenic compounds, could be considered as a standard therapy. These areas were discussed at the 4th Ovarian Cancer Consensus Conference.
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Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Ensaios Clínicos como Assunto/métodos , Terapia de Alvo Molecular/métodos , Neoplasias Ovarianas/tratamento farmacológico , Ensaios Clínicos como Assunto/tendências , Consenso , Descoberta de Drogas/tendências , Feminino , HumanosRESUMO
OBJECTIVES: To estimate the significance of hydronephrosis and impact of ureteral obstruction relief on outcome in patients with stage IIIB cervical cancer treated with radiation and concurrent chemotherapy. METHODS: We retrospectively studied stage IIIB cervical cancer patients treated on GOG trials 56, 85, 120 and 165 evaluating radiation and concurrent chemotherapy. Eligible patient records were reviewed to assess the presence of hydronephrosis and treatment of ureteral obstruction. Patients were classified into three groups; no hydronephrosis, hydronephrosis relieved from ureteral obstruction via stent or percutaneous nephrostomy and hydronephrosis without treatment of ureteral obstruction. RESULTS: 539 stage IIIB patients were studied. Hydronephrosis was present in 238 (44.2%). Patient age, race, and tumor characteristics (size, histology and grade) were not significantly different between patients with or without hydronephrosis. Patients with hydronephrosis received similar doses of radiation and cisplatin-based chemotherapy. Both overall and progression-free survival were worse with hydronephrosis (log-rank test p value=0.0189 and 0.0186, respectively). Univariable analysis identified five prognostic factors; pelvic nodal metastasis (p=0.0001), tumor diameter (p=0.0007), cisplatin-based concurrent chemoradiation (p=0.0031), hydronephrosis (p=0.0189), and performance status (p=0.0359). Hydronephrosis was associated with worse performance status (p<0.001). On multivariable analysis hydronephrosis was not a significant prognostic factor. Ureteral obstruction relief occurred for 88% of patients and was associated with improved survival. CONCLUSION: In patients with stage IIIB cervical cancer restricted to the pelvis, hydronephrosis at presentation is a significant but not independent prognostic factor associated with poor performance status and poorer survival. Relief of ureteral obstruction is correlated with improved outcome.
Assuntos
Hidronefrose/fisiopatologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do Tratamento , Obstrução Ureteral/fisiopatologia , Obstrução Ureteral/cirurgia , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: The objective of this study was to estimate antitumor activity and toxicity of weekly docetaxel and gemcitabine as second-line chemotherapy for patients with recurrent uterine carcinosarcoma. METHODS: Patients with recurrent carcinosarcoma of the uterus who had failed one regimen of chemotherapy, had a Gynecologic Oncology Group (GOG) performance status of 0-2 and had measurable disease were included. Treatment consisted of gemcitabine 600 mg/m(2) and docetaxel 35 mg/m(2) intravenously on days 1, 8 and 15 of a 28-day cycle until disease progression or intolerable adverse effects. This study employed an optimal but flexible two-stage design with an early stopping rule. If more than 3 out of 22-24 or more than 4 out of 25-29 patients responded, accrual to the second stage was to be initiated. RESULTS: Twenty-eight patients were enlisted. Three patients were not eligible after pathology review. One patient was never treated. Twenty-four patients were evaluable. Nine patients had previous radiation therapy. There were no complete responses. Partial responses were seen in two patients (8.3%), stable disease in eight (33.3%) and progressive disease in 12 patients (50%). Two patients were not evaluable (8.3%). The median progression-free survival was 1.8 months. The median survival was 4.9 months. The treatment caused myelosuppression, mainly neutropenia, but also thrombocytopenia and anemia. Dose modifications became necessary in the majority of patients. In five patients, treatment was discontinued due to toxicity. CONCLUSIONS: This regimen of docetaxel and gemcitabine is not active in patients with recurrent carcinosarcoma of the uterus as second-line chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinossarcoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Docetaxel , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Taxoides/administração & dosagem , Taxoides/efeitos adversos , GencitabinaRESUMO
OBJECTIVE: The objective of the study was to study posttherapy chemoradiation hysterectomy histology with long-term survival in bulky stage 1(B) cervical cancer patients. STUDY DESIGN: Gynecologic Oncology Group protocols 71 and 123 enrolled 464 patients randomly allocated to pelvic radiation (75 Gy, n = 291) plus hysterectomy (RTH) or to pelvic radiation (75 Gy) and cisplatin (40 mg/m(2), n = 176) plus hysterectomy (RTCH). Risk of progression and death were evaluated by posttherapy hysterectomy response (good: <10% viable; poor: ≥10% viable). RESULTS: Median survivor follow-up was 112 months. Relative risks of disease progression and death were 0.656 (95% confidence interval, 0.472-0.912) and 0.638 (95% confidence interval, 0.449-0.908), favoring RTCH. Good response patients (345; 74%) had similar 10 year overall survival (OS) and progression-free survival (PFS) after RTH or RTCH (P > .47). Poor response patients after RTCH had superior OS (P = .046) and PFS (P = .084). Extrapelvic recurrences occurred more often in poor response patients. CONCLUSION: Posttherapy viable residual disease less than 10% was associated with reduced risk of progression and cancer-related death.
Assuntos
Carcinoma/mortalidade , Carcinoma/terapia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma/patologia , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Progressão da Doença , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasia Residual , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: The Gynecologic Oncology Group (GOG) is a multi-institution, multi-discipline Cooperative Group funded by the National Cancer Institute (NCI) to conduct clinical trials which investigate the treatment, prevention, control, quality of survivorship, and translational science of gynecologic malignancies. In 1982, the NCI initiated a program of on-site quality assurance audits of participating institutions. Each is required to be audited at least once every 3 years. In GOG, the audit mandate is the responsibility of the GOG Quality Assurance Audit Committee and it is centralized in the Statistical and Data Center (SDC). Each component (Regulatory, Investigational Drug Pharmacy, Patient Case Review) is classified as Acceptable, Acceptable, follow-up required, or Unacceptable. PURPOSE: To determine frequently occurring deviations and develop focused innovative solutions to address them. METHODS: A database was created to examine the deviations noted at the most recent audit conducted at 57 GOG parent institutions during 2004-2007. Cumulatively, this involved 687 patients and 306 protocols. RESULTS: The results documented commendable performance: Regulatory (39 Acceptable, 17 Acceptable, follow-up, 1 Unacceptable); Pharmacy (41 Acceptable, 3 Acceptable, follow-up, 1 Unacceptable, 12 N/A): Patient Case Review (31 Acceptable, 22 Acceptable, follow-up, 4 Unacceptable). The nature of major and lesser deviations was analyzed to create and enhance initiatives for improvement of the quality of clinical research. As a result, Group-wide proactive initiatives were undertaken, audit training sessions have emphasized recurring issues, and GOG Data Management Subcommittee agendas have provided targeted instruction and training. LIMITATIONS: The analysis was based upon parent institutions only; affiliate institutions and Community Clinical Oncology Program participants were not included, although it is assumed their areas of difficulty are similar. CONCLUSIONS: The coordination of the GOG Quality Assurance Audit program in the SDC has improved data quality by enhancing our ability to identify frequently occurring deviations and develop innovative solutions to avoid or minimize their occurrence in the future.
Assuntos
Ensaios Clínicos como Assunto/normas , Neoplasias dos Genitais Femininos , Auditoria Médica/organização & administração , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Sistemas de Notificação de Reações Adversas a Medicamentos/organização & administração , Ensaios Clínicos como Assunto/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes/organização & administração , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Consentimento Livre e Esclarecido/normas , Consentimento Livre e Esclarecido/estatística & dados numéricos , Auditoria Médica/normas , Auditoria Médica/estatística & dados numéricos , Assistência Farmacêutica/organização & administração , Garantia da Qualidade dos Cuidados de Saúde/normas , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Resultado do TratamentoRESUMO
OBJECTIVE: To describe trends in mortality rates, in New York State, due to cervical, endometrial and ovarian cancer and to assess how these rates varied with proximity to a comprehensive cancer treatment center or population density (rural/urban). METHODS: Data were obtained from the Centers for Disease Control and Prevention (CDC)'s Compressed Mortality Files, Census Bureau records, and online maps. Poisson regression models were fitted to estimate death rates (mean number of deaths per 100,000 women per year) due to gynecologic cancer type. Trends in death rates were compared with respect to driving time to the nearest comprehensive cancer treatment center and population density, controlling for race, county income level, and age at death. RESULTS: Cervical and endometrial but not ovarian death rates declined over time. For both cervical and endometrial cancers, death rates varied significantly with driving time and between rural and urban counties. In the case of cervical cancer, the decline over time was steeper in rural than in urban counties. For endometrial cancer, the decline steepened with increasing distance from a treatment center. CONCLUSION: Improvements in cervical and endometrial cancer mortality from 1979 to 2001 followed increases in gynecologic cancer treatment research efforts, number of specialists trained to treat such cases, and in the emphasis on gynecologic cancer in the training of physicians in general. Our results are consistent with an interpretation that the progressive actions by leaders in the gynecologic oncology profession during the late 1960's and early 1970's contributed to improvements in mortality rates in subsequent decades.
Assuntos
Neoplasias dos Genitais Femininos/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Centers for Disease Control and Prevention, U.S. , Criança , Pré-Escolar , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Lactente , Pessoa de Meia-Idade , New York/epidemiologia , Neoplasias Ovarianas/mortalidade , Fatores Socioeconômicos , Estados Unidos , Neoplasias do Colo do Útero/mortalidade , Adulto JovemRESUMO
OBJECTIVE: To determine if low node count from superficial groin dissection correlated with first recurrence in the groin for patients with early vulvar cancer. METHODS: The Gynecologic Oncology Group (GOG) conducted a trial for patients with early stage squamous vulvar cancer, lesions <2 cm in size and <5 mm in depth. All fatty tissue below the inguinal ligament, medial to the sartorious and lateral to the adductor longus was removed. Incision of the fascia and skeletonizing the femoral vessels were not required. For this secondary analysis, we reviewed the records of all patients to assess node counts. RESULTS: Of the 113 patients eligible for the study, 104 patients (with 117 dissected groins) did not have a first recurrence in the groin. The median number of negative nodes was 9 (range: 1-26). Nine patients (with 9 dissected groins) suffered a first recurrence in the groin. The median number of negative nodes removed per groin was 7 (range: 4-22). There were no significant differences between patients with first recurrence in the groin and those without (p value=0.7475). There was a broad overlap of the confidence intervals. CONCLUSIONS: We were unable to show that groin failure after superficial lymphadenectomy was a result of low lymph node count. The small number of recurrences made firm conclusions impossible. Variations in anatomy and other factors may make node counting an unreliable measure of surgical quality.
Assuntos
Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Vulvares/patologia , Feminino , Humanos , Canal Inguinal/patologia , Canal Inguinal/cirurgia , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Vulvares/cirurgiaRESUMO
OBJECTIVE: The objective of the study was to confirm that concurrent cisplatin (CT) with radiation therapy (RT) is associated with improved long-term progression-free survival (PFS) and overall survival (OS), compared with RT alone in stage IB bulky carcinoma of the cervix, when both groups' therapy is followed by hysterectomy. STUDY DESIGN: Three hundred seventy-four patients entered this trial. There were 369 evaluable patients; 186 were randomly allocated to receive RT alone and 183 to receive CT plus RT. Radiation dosage was 45 Gray (Gy) in 20 fractions followed by low dose-rate intracavitary application(s) of 30 Gy to point A. Chemotherapy consisted of intravenous cisplatin 40 mg/m2 every week for up to 6 weekly cycles. Total extrafascial hysterectomy followed the completion of RT by 6-8 weeks. RESULTS: Preliminary results have been published, at which time there were 292 censored observations, and median duration of follow-up was only 36 months. Patient and tumor characteristics were well balanced between the regimens. The median patient age was 41.5 years; 81% had squamous tumors; 59% were white. Median follow-up is now 101 months. The relative risk for progression was 0.61 favoring CT plus RT (95% confidence interval [CI] 0.43 to 0.85, P < .004). At 72 months, 71% of patients receiving CT plus RT were predicted to be alive and disease free when adjusting for age and tumor size, compared with 60% of those receiving RT alone. The adjusted death hazard ratio was 0.63 (95% CI 0.43 to 0.91, P < .015) favoring CT plus RT. At 72 months, 78% of CT plus RT patients were predicted to be alive, compared with 64% of RT patients. An increased rate of early hematologic and gastrointestinal toxicity was seen with CT plus RT. There was no detectable difference in the frequency of late adverse events. CONCLUSION: Concurrent weekly cisplatin with RT significantly improves long-term PFS and OS when compared with RT alone. Serious late effects were not increased. The inclusion of hysterectomy has been discontinued on the basis of another trial. Pending further trials, weekly cisplatin with radiation is the standard against which other regimens should be compared.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adulto , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/radioterapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Progressão da Doença , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Histerectomia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgiaRESUMO
PURPOSE: The objectives of this prospective randomized study of consolidation therapy were to evaluate recurrence-free survival (RFS), overall survival (OS), and the morbidity of intraperitoneal (IP) chromic phosphate suspension (32P) therapy in patients with stage III epithelial ovarian carcinoma who have no detectable evidence of disease at the second-look laparotomy (SLL) procedure after primary chemotherapy. PATIENTS AND METHODS: In a multi-institution clinical cooperative trial, 202 eligible patients with a negative SLL were randomly selected to receive either 15 mCi IP 32P (n = 104) or no further therapy (NFT; n = 98). RESULTS: With a median follow-up of 63 months in living patients, 68 patients in the IP 32P group (65%) and 63 patients in the NFT group (64%) have developed tumor recurrence. The relative risk of recurrence is 0.90 (IP 32P to NFT) (90% confidence interval [CI], 0.68 to 1.19). The 5-year RFS rate is 42% and 36% for the IP 32P and NFT groups, respectively; the difference is not statistically significant (log-rank test, P =.27). There was no statistically significant difference in OS (P =.19). The relative risk of death is 0.85 (IP 32P to NFT) (90% CI, 0.62 to 1.16). Sixteen patients (8%) experienced grade 3 or 4 adverse effects, with eight in each respective group. CONCLUSION: Intraperitoneal chromic phosphate did not decrease the risk of relapse or improve survival for patients with stage III epithelial ovarian cancer after a negative SLL. Despite complete pathologic remission at SLL after initial surgery and platinum-based chemotherapy, 61% of stage III ovarian cancer patients had tumor recurrence within 5 years of negative SLL. This indicates a need for more effective initial therapy and further studies of consolidation therapy.