RESUMO
PURPOSE: To assess radiation therapy (RT)-induced vasculitis in patients with non-small cell lung cancer (NSCLC) by examining changes in the uptake of 18F-fluoro-D-deoxyglucose ([18F]FDG) by positron emission tomography/computed tomography (PET/CT) images of the ascending aorta (AA), descending aorta (DA), and aortic arch (AoA) before and after proton and photon RT. METHOD: Thirty-five consecutive locally advanced NSCLC patients were definitively treated with proton (n = 27) or photon (n = 8) RT and concurrent chemotherapy. The patients were prospectively enrolled to undergo [18F]FDG-PET/CT imaging before and 3 months after RT. An adaptive contrast-oriented thresholding algorithm was applied to generate mean standardized uptake values (SUVmean) for regions of interest (ROIs) 3 mm outside and 3 mm inside the outer perimeter of the AA, DA, and AoA. These ROIs were employed to exclusively select the aortic wall and remove the influence of blood pool activity. SUVmeans before and after RT were compared using two-tailed paired t-tests. RESULTS: RT treatments were associated with increased SUVmeans in the AA, DA, and AoA-1.9%, 0.3%, and 1.3% for proton and 15.8%, 9.5%, and 15.5% for photon, respectively. There was a statistically significant difference in the ∆SUVmean (post-RT SUVmean - pre-RT SUVmean) in patients treated with photon RT when compared to ∆SUVmean in patients treated with proton RT in the AA (p = 0.043) and AoA (p = 0.015). There was an average increase in SUVmean that was related to dose for photon patients (across structures), but that was not seen for proton patients, although the increase was not statistically significant. CONCLUSION: Our results suggest that patients treated with photon RT for NSCLC may exhibit significantly more RT-induced inflammation (measured as ∆SUVmean) in the AA and AoA when compared to patients who received proton RT. Knowledge gained from further analyses in larger cohorts could aid in treatment planning and help prevent the significant morbidity and mortality associated with RT-induced vascular complications. TRIAL REGISTRATION: NCT02135679.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Lesões por Radiação , Vasculite , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Prótons , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
This work explored the formation mechanism of marine oil snow (MOS) and the associated transport of oil hydrocarbons in the presence of a stereotype oil dispersant, Corexit EC9500A. Roller table experiments were carried out to simulate natural marine processes that lead to formation of marine snow. We found that both oil and the dispersant greatly promoted the formation of MOS, and MOS flocs as large as 1.6-2.1 mm (mean diameter) were developed within 3-6 days. Natural suspended solids and indigenous microorganisms play critical roles in the MOS formation. The addition of oil and the dispersant greatly enhanced the bacterial growth and extracellular polymeric substance (EPS) content, resulting in increased flocculation and formation of MOS. The dispersant not only enhanced dissolution of n-alkanes (C9-C40) from oil slicks into the aqueous phase, but facilitated sorption of more oil components onto MOS. The incorporation of oil droplets in MOS resulted in a two-way (rising and sinking) transport of the MOS particles. More lower-molecular-weight (LMW) n-alkanes (C9-C18) were partitioned in MOS than in the aqueous phase in the presence of the dispersant. The information can aid in our understanding of dispersant effects on MOS formation and oil transport following an oil spill event.
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Hidrocarbonetos/química , Lipídeos/química , Poluição por Petróleo , Petróleo , Poluentes Químicos da Água/química , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Biopolímeros/química , Biopolímeros/metabolismo , FloculaçãoRESUMO
Endocrine disrupting compounds (EDCs), represented by steroid hormones, organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and bisphenol A have been determined in four sediment cores from the Gulf of Mexico, from New Orleans surface water (Lake Pontchartrain and Mississippi River), and from the influent and effluent of a New Orleans municipal sewage treatment plant. During the five-month monitoring of selected EDCs in the Mississippi River (MR) and Lake Pontchartrain (LP) in 2008, 21 of 29 OCPs in MR and 17 of 29 OCPs in LP were detected; bisphenol A was detected in all of the samples. Steroid hormones (estrone, 17ß-estradiol and 17α-ethinylestradiol) were detected occasionally. Total EDC (OCPs + PCBs + steroid hormones + bisphenol A) concentrations in the two surface water samples were found to vary from 148 to 1112 ng L(-1). Strong correlation of the distribution of total OCPs, total PCBs and total EDCs between solid and water phases was found in LP, while moderate or no correlation existed in MR. OCPs, PCBs, steroid hormones, and bisphenol A were all detected in the ocean sediments, and total EDCs were measured in the range of 77 to 1796 ng g(-1) dry sediment weight. The EDCs were also found in untreated and treated municipal sewage samples with a removal efficiency of 83% for OCPs but no removal efficiency for 17α-ethinylestradiol.
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Disruptores Endócrinos/análise , Poluentes Químicos da Água/análise , Compostos Benzidrílicos , Etinilestradiol/análise , Água Doce/química , Sedimentos Geológicos/química , Golfo do México , Hidrocarbonetos Clorados/análise , Mississippi , Nova Orleans , Praguicidas/análise , Fenóis/análise , Bifenilos Policlorados/análise , Água do Mar/química , Poluição Química da Água/estatística & dados numéricosRESUMO
BACKGROUND: In the early 1990s, the role of adjuvant tamoxifen in premenopausal women with early breast cancer (EBC) was not established. Similarly, optimum timing relative to adjuvant chemotherapy and efficacy of tamoxifen in hormone receptor-negative tumors were unclear. PATIENTS AND METHODS: Premenopausal women with EBC, any hormone receptor status, after surgery received standard adjuvant chemotherapy [doxorubicin (adriamycin)/cyclophosphamide, cyclophosphamide/methotrexate/5-fluorouracil, or cyclophosphamide/epirubicin/5-fluorouracil] followed by randomization to tamoxifen or placebo for 5 years. Outcomes were overall survival (OS), disease-free survival (DFS), toxicity, and compliance with therapy. RESULTS: Median follow-up for 672 women was 9.7 years. Multivariate analysis showed improved DFS [78.2% versus 71.3% at 5 years; hazard ratio (HR) 0.77; P = 0.056] and a trend for improved OS (86.6% versus 82.1% at 5 years; HR 0.78; P = 0.12). There was no evidence of greater benefit for the receptor-positive subgroup. Compliance with treatment was suboptimal in both arms, with 103 (31%) women on tamoxifen and 70 (21%) on placebo-stopping therapy early because of toxicity, refusal, or other choices. CONCLUSIONS: Adjuvant tamoxifen, given after chemotherapy to premenopausal women with EBC, improved 5-year DFS. Poor compliance may have reduced treatment efficacy.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Pré-Menopausa , Tamoxifeno/administração & dosagem , Academias e Institutos , Adulto , Antineoplásicos/administração & dosagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Canadá , Quimioterapia Adjuvante , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Excisão de Linfonodo , Mastectomia/métodos , Pessoa de Meia-Idade , Placebos , Pré-Menopausa/efeitos dos fármacos , Análise de Sobrevida , Fatores de TempoRESUMO
The 2010 Deepwater Horizon (DwH) oil spill contaminated ~1,773km of the Gulf of Mexico shorelines. Yet, few field data are available on the long-term fate and persistency of sediment-retained oil. While an unprecedented amount of oil dispersants was applied, the effects of oil dispersants on desorption of field aged oil remain unknown. This study aimed to investigate the abundance, distributions and physico-chemical availability of the oil retained in Bay Jimmy sediment, Louisiana, five years after the DwH oil spill, and to determine the effects of two model oil dispersants on the desorption potential of the residual oil. Total petroleum hydrocarbons (TPHs), n-alkanes and polycyclic aromatic hydrocarbons (PAHs) in the sediment were analyzed and compared with those in the crude oil and the pre-DwH levels, and batch desorption kinetic tests were carried out to quantify the dispersant effects on the desorption rate and extent. The biomarker hopanes profile and diagnostic ratio were analyzed, which confirmed the origin and persistence of the sediment-retained oil. After five-year natural weathering, the oil level in the sediment remained orders of magnitude higher than the pre-spill level. Nearly all low-molecular-weight n-alkanes and 2-ring PAHs had been degraded. Oil dispersants, SPC 1000 and Corexit EC9500A, were able to enhance solubilization of the sediment-retained oil upon resuspension of the sediment. Successive desorption experiments indicated that 71.6% of TPHs, 74.8% of n-alkanes, and 91.9% of PAHs in the sediment remained highly stable and hardly desorbable by seawater; yet, addition of 18mg/L of SPC 1000 enhanced the desorption and lowered these fractions to 57.3%, 68.1%, and 81.4%, respectively. The findings are important for understanding the natural weathering rate and persistence of oil residual and the effects of dispersants on the physical and biological availabilities of aged oil in coastal sediments.
RESUMO
This study investigated the effects of 3 model oil dispersants (Corexit EC9500A, Corexit EC9527A and SPC 1000) on photodegradation of pyrene under simulated sunlight. Both Corexit dispersants enhanced photodegradation of pyrene, while SPC1000 slightly inhibited the reaction. Span 80 and Tween 85 were the key ingredients causing the effects, though the underlying mechanisms differed. Span 80 enriches pyrene in the upper layer of water column, whereas Tween 85 induces a photosensitization process. Two reactive oxygen species, 1O2 and O2-, were found responsible for pyrene photodegradation, though the presence of EC9500A suppressed the 1O2 pathway. In terms of photodegradation products, EC9500A enhanced generation of polyaromatic intermediates, i.e., phenaleno[1,9-cd][1,2]dioxine, 1-hydroxypyrene, and 1,8-pyrenequinone, but did not alter the classical photodegradation pathway. The Corexit dispersants were more prone to photochemical decomposition, with multiple by-products detected. The information aids in our understanding of the effects of dispersants on photochemical weathering of oil compositions.
Assuntos
Modelos Teóricos , Petróleo/análise , Fotólise , Pirenos/análise , Água do Mar/química , Luz Solar , Poluentes Químicos da Água/análise , Petróleo/efeitos da radiação , Poluição por Petróleo/análise , Pirenos/química , Pirenos/efeitos da radiação , Espécies Reativas de Oxigênio/análise , Poluentes Químicos da Água/química , Poluentes Químicos da Água/efeitos da radiaçãoRESUMO
This study investigated effects of three model oil dispersants on photodegradation of two model PAHs (anthracene and 9,10-dimethyanthracene (9,10-DMA)) under simulated sunlight. All three dispersants, i.e. Corexit EC9500A, Corexit EC9527A and SPC 1000, promoted the photolysis rate of 9,10-DMA, following the order of Corexit EC9500A > Corexit EC9527A > SPC 1000. The photodegradation rate was well interpreted by a two-stage, first-order kinetic law with a faster initial photolysis rate in the presence of the dispersants. Span 80, Tween 85 and kerosene were found as the key dispersant components, of which Span 80 and Tween 85 promoted the photodegradation by boosting absorbance of solar irradiation while kerosene by dispersing more PAHs in the upper layer of the water column. Dissolved oxygen (DO) inhibited photolysis of anthracene regardless of dispersant resulting from quenching the excited states of the PAH, while DO facilitated photolysis of 9,10-DMA due to the formation singlet oxygen (1O2) radicals in the presence of oil dispersants. The other ROS, i.e. â¢O2- and â¢OH, played a negligible role on the photodegradation of anthracene and 9,10-DMA. Fluorescence analysis showed that more anthracene was associated with dispersant than 9,10-DMA, which favored the direct transfer of energy to anthracene, while energy is more likely transferred to oxygen to form 1O2 in the case of 9,10-DMA. Direct photolysis dominated the photodegradation of anthracene and 9,10-DMA. Both direct ionization of anthracene and the electron transfer from excited 9,10-DMA to oxygen can lead to formation of the corresponding PAH radical cations. Overall, the oil dispersants accelerated the photolysis rates of the PAHs without altering the degradation pathway. The findings are useful for understanding photochemical weathering of dispersed oil components in the environment.
Assuntos
Antracenos/química , Água do Mar/química , Tensoativos/química , Poluentes Químicos da Água/química , Alquilantes , Cinética , Poluição por Petróleo , Processos Fotoquímicos , Fotólise , Hidrocarbonetos Policíclicos Aromáticos/análise , Luz Solar , Água , Poluentes Químicos da Água/análiseRESUMO
This work investigated effects of three model oil dispersants (Corexit EC9527A, Corexit EC9500A and SPC1000) on settling of fine sediment particles and particle-facilitated distribution and transport of oil components in sediment-seawater systems. All three dispersants enhanced settling of sediment particles. The nonionic surfactants (Tween 80 and Tween 85) play key roles in promoting particle aggregation. Yet, the effects varied with environmental factors (pH, salinity, DOM, and temperature). Strongest dispersant effect was observed at neutral or alkaline pH and in salinity range of 0-3.5wt%. The presence of water accommodated oil and dispersed oil accelerated settling of the particles. Total petroleum hydrocarbons in the sediment phase were increased from 6.9% to 90.1% in the presence of Corexit EC9527A, and from 11.4% to 86.7% for PAHs. The information is useful for understanding roles of oil dispersants in formation of oil-sediment aggregates and in sediment-facilitated transport of oil and PAHs in marine eco-systems.
Assuntos
Sedimentos Geológicos/análise , Modelos Teóricos , Petróleo/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Tensoativos/química , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio , Cinética , Poluição por Petróleo/análise , Salinidade , Água do Mar/química , TemperaturaRESUMO
This work developed a new method to determine concentration of Corexit EC9500A, and likely other oil dispersants, in seawater. Based on the principle that oil dispersants decrease surface tension, a linear correlation was established between the dispersant concentration and surface tension. Thus, the dispersant concentration can be determined by measuring surface tension. The method can accurately analyze Corexit EC9500A in the concentration range of 0.5-23.5mg/L. Minor changes in solution salinity (<0.3%), pH (7.9-9.0), and dissolved organic matter (<2.0mg/L as TOC) had negligible effects on the measurements. Moreover, effects of extracts from marine sediments were negligible, and thus, the method may be directly applied to seawater-sediment systems. The method accuracy was confirmed by comparing with direct TOC analysis. This simple, fast, economical method offers a convenient analytical tool for quantifying complex oil dispersants in water/seawater, which has been desired by the oil spill research community and industries.
Assuntos
Poluição por Petróleo , Água do Mar , Tensão Superficial , Poluentes Químicos da Água , Petróleo , TensoativosRESUMO
This work examined effects of model oil dispersants on dispersion, sorption and photodegradation of petroleum hydrocarbons in simulated marine systems. Three dispersants (Corexit 9500A, Corexit 9527A and SPC 1000) were used to prepare dispersed water accommodated oil (DWAO). While higher doses of dispersants dispersed more n-alkanes and PAHs, Corexit 9500A preferentially dispersed C11-C20 n-alkanes, whereas Corexit 9527A was more favorable for smaller alkanes (C10-C16), and SPC 1000 for C12-C28 n-alkanes. Sorption of petroleum hydrocarbons on sediment was proportional to TPH types/fractions in the DWAOs. Addition of 18mg/L of Corexit 9500A increased sediment uptake of 2-3 ring PAHs, while higher dispersant doses reduced the uptake, due to micelle-enhanced solubilization effects. Both dispersed n-alkanes and PAHs were susceptible to photodegradation under simulated sunlight. For PAHs, both photodegradation and photo-facilitated alkylation were concurrently taking place. The information can facilitate sounder assessment of fate and distribution of dispersed oil hydrocarbons in marine systems.
Assuntos
Petróleo , Fotólise , Água do Mar , Sedimentos Geológicos , Hidrocarbonetos , Poluição por Petróleo , Poluentes Químicos da ÁguaRESUMO
Elderly patients with advanced-stage diffuse large-cell lymphomas (DLCLs) are either excluded from or under-represented in most clinical trials of combination chemotherapy regimens because they tolerate treatment poorly and usually have a worse outcome. We report two brief weekly chemotherapy regimens designed specifically for elderly patients. Eligible patients were aged 65 to 85 years, had advanced-stage DLCL (diffuse mixed, diffuse large-cleaved or noncleaved, immunoblastic, or diffuse large-cell not otherwise specified). Advanced stage was defined as Ann Arbor stage III or IV or stage I or II with a mass greater than 10 cm or B symptoms. Low-dose doxorubicin, cyclophosphamide, vincristine, bleomycin, and prednisone (LD-ACOP-B) accrued 40 patients between March 1983 and September 1985; 65% achieved a complete response (CR), there were two toxic deaths, the actuarial failure-free survival (FFS) is 19%, disease-specific survival (DSS) 30%, and overall survival (OS) 28%, with a maximum follow-up of 6 years. The regimen of etoposide, doxorubicin, vincristine, bleomycin, and prednisone (VABE) accrued 32 patients between July 1985 and June 1987; 63% achieved a CR, there were two toxic deaths, and the actuarial FFS is 34%, DSS 45%, and OS 36%, with a maximum follow-up of 4 years. There is no difference in FFS, DSS, or OS between these two regimens. VABE caused more myelosuppression and infectious complications, although the toxic death rates were similar. We prefer LD-ACOP-B because follow-up is longer and toxicity is less.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Análise de Sobrevida , Vincristina/administração & dosagemRESUMO
PURPOSE: To examine the clinical course of patients who experienced a late relapse after initial curative chemotherapy for advanced-stage diffuse large-cell lymphoma. PATIENTS AND METHODS: Between April 1981 and June 1986, 127 patients with de novo advanced-stage diffuse large-cell lymphoma were treated with a 12-week chemotherapy program (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]). The overall survival rate at 10 years is 52%. One hundred six patients (83%) entered a complete remission (CR) and 43 of them relapsed. With a median follow-up duration of 146 months, 26 patients relapsed early and 17 relapsed late, ie, after a continuous CR (cCR) of greater than 24 months. All late relapses occurred in patients with B-cell lymphoma. RESULTS: After 24 months from diagnosis, the rate of late relapse averaged 2.2% per year and reached a projected 22% actuarial risk of late relapse after 10 years. The median time to late relapse was 69 months (range, 38 to 141). Ten patients relapsed with aggressive histologic subtypes and were treated with curative intent using anthracycline-based chemotherapy. Four remain in second CR, one is alive with disease, and five died of disease or while on treatment. The 6-year overall survival rate from the time of relapse (SFR) for these 10 patients is 42%. Six patients relapsed with low-grade follicular lymphoma. These patients received various treatments intended to control, but not necessarily cure disease. One is in second CR, one is alive with disease, and four died of disease or while on treatment. The 6-year overall SFR rate for these six patients is 40%. bcl-2 translocation and Bcl-2 protein expression at diagnosis did not predict for the type of late relapse. One patient did not undergo repeat biopsy at relapse and died 9 months later despite aggressive therapy. CONCLUSION: Curative therapy should be attempted in patients who relapse late with aggressive-histology lymphoma and those who relapse with follicular histology may benefit from palliative treatment. The behavior of late-relapse lymphoma is similar to de novo lymphoma, with outcome dictated by the histologic subtype at relapse.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Terapia de Salvação , Adulto , Biomarcadores Tumorais/metabolismo , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Leucovorina/administração & dosagem , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Recidiva , Taxa de Sobrevida , Fatores de Tempo , Vincristina/administração & dosagemRESUMO
PURPOSE: To establish the optimum biologic dose and maximal-tolerated dose (MTD) of once-daily, subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor derived from yeast (RhuGM-CSF) in patients with breast cancer. PATIENTS AND METHODS: Seventeen patients with either newly diagnosed breast cancer with more than four involved axillary nodes (five patients) or metastatic breast cancer (12 patients) were treated with cyclophosphamide 1 g/m2, doxorubicin 50 mg/m2, and fluorouracil 500 mg/m2 (CAF) intravenously (IV) once every 3 weeks. RhuGM-CSF was administered subcutaneously once daily for 14 days after the second and third CAF cycles, at one of three dose levels. RESULTS: The 125-micrograms/m2/d RhuGM-CSF dose level shortened the duration of neutropenia in only one of three patients. The 250-micrograms/m2/d level was effective in shortening the duration of the neutropenic nadir (< .5 x 10(9)/dL) by 2 or more days in five of six patients. The 500-micrograms/m2/d level caused severe toxicity (chest pain, two patients; deep vein thrombosis, one patient) in three of eight patients. CONCLUSION: RhuGM-CSF administered once daily at the 250-micrograms/m2/d level is well tolerated and effective in shortening the duration of the neutrophil nadir by 2 or more days after CAF therapy.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Neutropenia/prevenção & controle , Adulto , Idoso , Quimioterapia Adjuvante , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Feminino , Fluoruracila/efeitos adversos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Humanos , Injeções Subcutâneas , Metástase Linfática , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Saccharomyces cerevisiaeRESUMO
PURPOSE: The results of a prospective, phase II trial of an 8-week treatment program consisting of epirubicin or doxorubicin, vincristine, cyclophosphamide, etoposide, and prednisone (P/DOCE) for elderly patients with advanced large-cell lymphoma are reported and compared with previous phase II studies conducted in similar patients at the same institution. PATIENTS AND METHODS: Between March 1988 and September 1991, 63 previously untreated patients aged 65 to 85 years (median, 75) with advanced-stage diffuse large-cell lymphoma, defined as Ann Arbor stage III or IV or stage I or II with B symptoms or bulky disease, were enrolled on a brief, 8-week protocol consisting of five outpatient chemotherapy treatments. RESULTS: The complete response (CR) rate was 62%. The treatment-related mortality rate was 8%, the actuarial 4-year failure-free survival (FFS) rate was 41%, and the overall survival (OS) rate was 45%. These results were compared with two earlier, 12-week protocols, low-dose doxorubicin, cyclophosphamide, vincristine, bleomycin, and prednisone (LD-ACOB-B) and etoposide, doxorubicin, bleomycin, and prednisone (VABE), performed at the same center. There was no difference in outcome among the three regimens. If all 133 patients treated on any one of these three specially designed regimen for elderly patients are combined, the projected 5-year OS rate is 38%. CONCLUSION: The 8-week P/DOCE chemotherapy regimen is equal in efficacy and similar in toxicity to 3 months of chemotherapy administered on a weekly schedule and similar to the results reported in the literature for longer, anthracycline-based chemotherapy treatments. There does not appear to be any improvement in outcome from more protracted treatment programs compared with the 8-week P/DOCE protocol.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Prednisona/administração & dosagem , Probabilidade , Prognóstico , Estudos Prospectivos , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
PURPOSE: At the end of the 1970s it was thought that advanced epithelial ovarian cancer (EOC) could be cured by multimodality treatment using surgery, cisplatin-based combination chemotherapy, and radiotherapy (RT). Such multimodality treatment was used as standard therapy at our institution. Our long-term results are reviewed. PATIENTS AND METHODS: One hundred ninety-five previously untreated patients with stage III or IV EOC were treated between April 1979 and December 1982. All patients were to have debulking surgery, when feasible, followed by the administration of doxorubicin and cisplatin at 50 mg/m2 every 3 weeks until a total dose of doxorubicin of 450 mg/m2 had been reached. RT was used in addition in patients with disease remaining after the chemotherapy. Maintenance chemotherapy with oral cyclophosphamide and hexamethylmelamine (altretamine) was administered to patients who did not have a documented histologic complete remission. RESULTS: The 10-year overall and failure-free survivals were 4% and 8%, respectively. The median overall survival was 2 years. The achievement of a histologic complete response (n = 32) did not equate to cure because 20 (63%) of the patients eventually relapsed. Multivariate analysis identified residual disease of greater or less than 2 cm as the only independent prognostic factor. CONCLUSIONS: Our multimodality treatment program was noncurative for the majority of the patients. Innovative therapies are needed before we can hope to cure such disease.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/terapia , Neoplasias Ovarianas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Terapia Combinada , Doxorrubicina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To determine the maximum-tolerated dose of escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ) administered biweekly with a fixed dose of cisplatin, to assess the toxicity, and to evaluate the activity of this combination in a phase I/II trial in metastatic breast cancer. PATIENTS AND METHODS: Twenty-nine women with metastatic breast cancer were enrolled; 27 were assessable for response and 29 for toxicity. All but two of the women had received prior adjuvant chemotherapy, with 23 receiving anthracyclines and six previous cisplatin. RESULTS: The initial starting dose of paclitxel 90 mg/m2 and cisplatin 60 mg/m2 became the phase II dose due to dose-limiting neutropenia. Responses were seen in 85% of assessable patients, with three patients (11%) achieving a complete response (CR) and 20 patients (14%) a partial response (PR), for an overall response rate of 85% (95% confidence interval [CI], 66% to 96%). The time to disease progression for patients who achieved a CR was 110 to 200 days, and for those with a PR, it was 96 to 377+ days, with a median time to progression of 7.1 months and a median response duration of 7.9 months. Sites of CR were skin, soft tissue, and lung, and all occurred in women with previous exposure to anthracyclines. Septic events were rare, with two grade 3 infections (7%), only one of which required hospital admission. There were no grade 4 nonhematologic toxicity and minimal grade 3 toxicity. A total of 251 chemotherapy cycles were given -- 16 with paclitaxel alone in five patients. Forty-five percent of patients required dose reductions, while 52% had delays due to neutropenia. CONCLUSION: Biweekly paclitaxel and cisplatin is an active combination in the treatment of metastatic breast cancer, including for patients with previous exposure to anthracyclines.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Cisplatino/administração & dosagem , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Resultado do TratamentoRESUMO
PURPOSE: This randomized, prospective trial compares outcomes for patients with advanced Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, and vinblastine (ABV) hybrid regimen or alternating MOPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). METHODS: Three hundred one patients with advanced Hodgkin's disease were randomized to receive MOPP/ ABV hybrid regimen or alternating MOPP/ABVD after stratification for prior treatment, B symptoms, and treatment center. Eligible patients were either previously untreated and found to have stage IIIB, IVA, or IVB disease or previously treated with wide-field irradiation. Responding patients received a minimum of eight cycles of chemotherapy. Those with residual disease in a localized region received irradiation between the sixth and seventh cycle of treatment. RESULTS: Response rates to the two regimens were similar. Five-year overall survival rates were 81% and 83% for MOPP/ABV hybrid and alternating MOPP/ ABVD, respectively (P = .74; 95% confidence interval [CI] for the difference, -11% to 7%). Five-year failure-free survivals were 71% and 67% for MOPP/ABV hybrid and alternating MOPP/ABVD, respectively (P = .87; 95% CI for the difference, -9% to 17%). Significantly more episodes of febrile neutropenia and stomatitis were observed with the MOPP/ABV hybrid regimen; there was no significant difference in fatal toxicity. Patients with predefined, high-quality partial responses (PR-1s) had results similar to those with complete responses (CRs). Planned subset analysis showed no significant difference in outcome between the two arms of the trial for patients with newly diagnosed disease (5-year failure-free survival rates were 70% for MOPP/ABV hybrid and 59% for alternating MOPP/ABVD; P = .180), but superiority of alternating MOPP/ABVD for patients with prior irradiation (5-year failure-free survival 94% v 73%; P = .017). CONCLUSION: MOPP/ABV hybrid and alternating MOPP/ABVD regimens are equally effective for patients with advanced Hodgkin's disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Análise Atuarial , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Canadá , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Mecloretamina/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vincristina/administração & dosagemRESUMO
This work investigated effects of a popular oil dispersant (Corexit EC9500A) on UV- or sunlight-mediated photodegradation of pyrene (a model polycyclic aromatic hydrocarbon) in seawater. The presence of 18 and 180mg/L of the dispersant increased the first-order photodegradation rate by 5.5% and 16.7%, respectively, and reduced or ceased pyrene volatilization. By combining individual first-order rate laws for volatilization and photodegradation, we proposed an integrated kinetic model that can adequately predict the overall dissipation of pyrene from seawater. Mechanistic studies indicated that superoxide radicals played a predominant role in pyrene photodegradation, and the dispersant enhanced formation of superoxide radicals. 1-Hydroxypyrene was the main intermediate regardless of the dispersant, suggesting that electrons were transferred from excited pyrene to oxygen. In the presence of 18mg/L of the dispersant, the photodegradation rate increased with increasing ionic strength and temperature, but decreased with increasing HA concentration, and remained independent of solution pH. The results are important in understanding roles of oil dispersants on environmental fate of persistent oil components in natural and engineered systems.
Assuntos
Misturas Complexas/química , Fotólise/efeitos dos fármacos , Propilenoglicóis/química , Pirenos/química , Ácidos Sulfônicos/química , Tensoativos/química , Substâncias Húmicas , Concentração de Íons de Hidrogênio , Concentração Osmolar , Espécies Reativas de Oxigênio/química , Água do Mar/química , Espectrofotometria Ultravioleta , Temperatura , Raios Ultravioleta , Volatilização/efeitos dos fármacosRESUMO
This work investigated effects of a prototype oil dispersant on solubilization, sorption and desorption of three model PAHs in sediment-seawater systems. Increasing dispersant dosage linearly enhanced solubility for all PAHs. Conversely, the dispersant enhanced the sediment uptake of the PAHs, and induced significant desorption hysteresis. Such contrasting effects (adsolubilization vs. solubilization) of dispersant were found dependent of the dispersant concentration and PAH hydrophobicity. The dual-mode models adequately simulated the sorption kinetics and isotherms, and quantified dispersant-enhanced PAH uptake. Sorption of naphthalene and 1-methylnaphthalene by sediment positively correlated with uptake of the dispersant, while sorption of pyrene dropped sharply when the dispersant exceeded its critical micelle concentration (CMC). The deepwater conditions diminished the dispersant effects on solubilization, but enhanced uptake of the PAHs, albeit sorption of the dispersant was lowered. The information may aid in understanding roles of dispersants on distribution, fate and transport of petroleum PAHs in marine systems.
Assuntos
Sedimentos Geológicos/química , Hidrocarbonetos Policíclicos Aromáticos/química , Água do Mar/química , Poluentes Químicos da Água/química , Adsorção , Cinética , Modelos Teóricos , Naftalenos/análise , Naftalenos/química , Poluição por Petróleo/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Solubilidade , Movimentos da Água , Poluentes Químicos da Água/análise , Purificação da Água/métodosRESUMO
An ongoing phase I/II trial in patients with chemotherapy-naive metastatic breast cancer (one adjuvant chemotherapy regimen is allowed) uses a 3-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 90 mg/m2 followed by a 3-hour infusion of cisplatin 60 mg/m2 every 2 weeks given with standard premedications. The protocol called for the escalation of paclitaxel in 10 mg/m2 increments to as much as 130 mg/m2 combined with a fixed 60 mg/m2 cisplatin dose without granulocyte colony-stimulating support in the phase I portion of the trial, but dose-limiting neutropenia identified the initial 90 mg/m2 paclitaxel dose as the maximum tolerated in this biweekly schedule. The phase II portion is continuing to accrue patients and results are preliminary. Twenty-two patients have been enrolled thus far. Of the 16 evaluable for response, four (25%) have had a complete and II (69%) a partial response, for an overall response rate of 94%. Eighteen patients are evaluable for toxicity. Significant neutropenia has been dose limiting, but the mean duration of the absolute neutrophil nadir (< 0.5 x 10(9)/L) is only 2 days. Nonhematologic toxicity has been generally mild, with no grade 4 and few grade 3 toxicities occurring. Nausea, most likely attributable to cisplatin, has occurred frequently, as have mild hypersensitivity reactions. Other nonhematologic toxicity (arthralgias, fatigue, neurologic symptoms) also has been mild.