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1.
Clin Nucl Med ; 46(1): e40-e43, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32804768

RESUMO

Sarcoidosis is a systemic disorder of unknown etiology characterized by development of noncaseating granulomas in more than 1 organ system. Development of sarcoidosis during or immediately after chemotherapy and immunotherapy is not uncommon. We present a 61-year-old woman in whom restaging F-FDG PET/CT detected asymptomatic sarcoidosis after neoadjuvant chemoradiotherapy for carcinoma rectum, which resolved spontaneously by the end of adjuvant chemotherapy with no specific treatment. Recognition of anatomic-metabolic pattern of sarcoidosis could prevent erroneous upstaging of the primary malignancy during restaging PET/CT following chemotherapy, and such lesions may show self-resolution.


Assuntos
Fluordesoxiglucose F18 , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Sarcoidose/etiologia , Quimioterapia Adjuvante/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/terapia , Remissão Espontânea , Sarcoidose/patologia
2.
Medicine (Baltimore) ; 99(50): e23633, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327342

RESUMO

BACKGROUND: Transient receptor potential vanilloid 2 (TRPV2) was previously shown to play an important role in the maintenance of cancer stem cells, and its specific inhibitor, tranilast, also has potential as a targeted therapeutic agent for esophageal squamous cell carcinoma (ESCC). The present study is being conducted to confirm the safety and efficacy of the additional use of tranilast with conventional preoperative adjuvant chemotherapy for patients with advanced ESCC. PATIENTS AND METHODS: Between 56 and 59 patients aged between 20 and 74 years with clinically diagnosed Stage II or Stage III ESCC will be enrolled. Eligible patients will receive preoperative adjuvant chemotherapy, 2 cycles of combination therapy with cisplatin, 5-fluorouracil, and tranilast. Recruitment started in November 2019, with the final follow-up being planned for March 2029. One subject has been enrolled since October 21, 2020. The pathological therapeutic effect is the primary endpoint. The objective response rate, safety of preoperative adjuvant chemotherapy, recurrence-free survival (RFS), and overall survival (OS) are the secondary endpoints. RFS and OS will be calculated as the time from surgery to first recurrence and all-cause death, respectively. ETHICS AND DISSEMINATION: This protocol has been approved by the Institutional Review Boards of Kyoto Prefectural University of Medicine and all participating hospitals in August 30, 2019 (Number: CRB5180001). Written informed consent will be obtained from all patients before their registration, which is in accordance with the Declaration of Helsinki. The results of the present study will be disseminated via publication in peer-reviewed journals. TRIAL REGISTRATION: Trial registration number jRCTs051190076.


Assuntos
Quimioterapia Adjuvante/métodos , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , ortoaminobenzoatos/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Cisplatino/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Análise de Sobrevida , Adulto Jovem , ortoaminobenzoatos/administração & dosagem , ortoaminobenzoatos/efeitos adversos
4.
Farm. hosp ; 44(5): 192-197, sept.-oct. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-195146

RESUMO

OBJETIVO: Estudiar los excipientes e impurezas de los diferentes medicamentos comercializados de docetaxel y conocer la incidencia de los diversos eventos adversos derivados del uso de docetaxel y su repercusión clínica en pacientes con cáncer de mama en el contexto de adyuvancia o neoadyuvancia. MÉTODO: Estudio observacional, longitudinal, prospectivo y multicéntrico en 26 hospitales de Madrid, Cataluña, Andalucía y Comunidad Valenciana. Se caracterizaron las distintas formulaciones de docetaxel en cuanto a pH, cantidad de docetaxel e impurezas. Se evaluó la incidencia acumulada de eventos adversos de cualquier grado estratificados por tipo de medicamento, analizando las diferencias mediante el test de χ2.RESULTADOS: Se detectaron diferencias estadísticamente significativas entre las distintas formulaciones de docetaxel en cuanto a la incidencia acumulada por ciclo de: modificación de dosis, anemia, reacciones de hipersensibilidad y anafilaxia, neuropatía, toxicidad palmo-plantar y dermatológica, toxicidad ungueal y edema facial. La formulación con un menor contenido en impurezas presentó mejores resultados en modificación de dosis, visitas a urgencias, e incidencia de anemia y edema facial, pero peores en hospitalización, neutropenia febril, neuropatía motora y toxicidad palmo-plantar. CONCLUSIONES: Los resultados muestran diferencias en la incidencia de los eventos adversos de los distintos medicamentos con docetaxel comercializados en nuestro país, con diferencias significativas entre ellos en algunas de las variables estudiadas. No se ha podido identificar un medicamento con un mejor perfil de toxicidad. Tampoco se ha podido establecer su relación con respecto a la composición de excipientes e impurezas


OBJECTIVE: To analyze the excipients and impurities contained in the various docetaxel products available on the market and find out whether they may be responsible for any of the different adverse events associated with the use of docetaxel in patients with breast cancer receiving adjuvant or neoadjuvant treatment. METHOD: This is a prospective, multicenter, longitudinal observational, study carried in 26 hospitals in Madrid, Catalonia, Andalusia, and the Valencia Region. The different docetaxel formulations were characterized in terms of their pH, amount of the active ingredient and impurities. The cumulative incidence of adverse events of any grade was evaluated. Adverse events were stratified by drug type and differences were analyzed by means of a chi-square test. RESULTS: Statistically significant differences were found between the different docetaxel formulations in the cumulative per-cycle incidence of: dosage change, anemia, hypersensitivity reactions and anaphylaxis, neuropathy, palmoplantar and dermal toxicity, ungual toxicity and facia edema. The formulation with the lowest content of impurities showed better results in terms of change of dosage, visits to the emergency room and incidence of anemia and facial edema. However, it was associated with poorer results regarding hospitalization, febrile neutropenia, motor neuropathy and palmoplantar toxicity. CONCLUSIONS: The results of the study showed differences in the incidence of adverse events of the different docetaxel products available in Spain. Such differences were statistically significant for some of the variables analyzed. The study was not able to determine which of the products offered the best toxicity profile. Nor was it possible to establish a correlation with respect to the composition of excipients or the content of impurities


Assuntos
Humanos , Feminino , Docetaxel/toxicidade , Neoplasias da Mama/tratamento farmacológico , Docetaxel/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Medicamentos Genéricos/efeitos adversos , Estudos Longitudinais , Estudos Prospectivos , Contaminação de Medicamentos
5.
PLoS One ; 15(10): e0240994, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33108394

RESUMO

Extracellular vesicles (EVs) are subcellular membrane blebs that include exosomes and microparticles, which represent a potential source for cancer biomarker discovery. We assess EVs characteristics as a tool to evaluate the endothelial and anti-tumor treatment injury during adjuvant chemotherapy in breast (BC) and colon cancer (CC) patients. Blood samples were taken from 29 BC and 25 CC patients before and after chemotherapy, as well as from healthy control donors (HC). Circulating blood EVs were isolated and characterized by size/concentration, membrane antigens for cell origin, thrombogenicity, and protein content. We observed higher EVs concentration and particle size in CC patients after chemotherapy compared with HC. Higher levels of endothelial EVs (CD144-positive) and vascular endothelial growth factor receptor 1 (VEGFR1), apparently as an indication of endothelial dysfunction, were found in all cancer patients, regardless of a given treatment, compared to HC. Levels of EVs labeled CD62E, CD34+41-, the lymphocyte markers CD11+ and CD-14+, Annexin-V, and the coagulation proteins TF and TFPI, however, sometimes demonstrate significant differences between patients, although HC did not show significant differences between patients pre- and post-chemotherapy. Most importantly, increasing levels of EVs encapsulated Angiostatin were found in patients with CC, while chemotherapy treatment leads to its notable rise in circulating blood EVs. Our results demonstrate the potential of EVs encapsulated Angiostatin as a tool to evaluate endothelial damage during adjuvant chemotherapy in BC and CC patients.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Vesículas Extracelulares/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Caderinas/análise , Estudos de Casos e Controles , Neoplasias do Colo/sangue , Neoplasias do Colo/patologia , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue
6.
Int J Clin Oncol ; 25(12): 2075-2082, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32785799

RESUMO

BACKGROUND: Chemotherapy with oxaliplatin is known to induce sinusoidal obstruction syndrome (SOS). In a previous single-center study, we reported that oxaliplatin-induced increase in splenic volume (SV) is strongly indicative of SOS, and that this increase in SV persisted for > 1 year after completing chemotherapy. The aim of this study was to confirm the oxaliplatin-induced SV change in a multicenter study in patients with stage III colon cancer in Japan. METHODS: We enrolled 59 patients who underwent curative resection for stage III colon cancer in the FACOS study in a phase II multi-center clinical study. Participants received mFOLFOX6 or CAPOX as adjuvant chemotherapy. SV change was assessed three times by computed tomographic volumetry: before surgery, on completion of adjuvant chemotherapy, and 1 year after completing adjuvant chemotherapy. RESULTS: SV on completing and 1 year after chemotherapy was significantly higher than that before surgery (P < 0.001). Oxaliplatin-induced SOS persisted for > 1 year after the completion of adjuvant chemotherapy in half of the patients. There was no difference in 3-year disease-free survival with respect to the presence or absence of increased SV. An increase in SV was observed in 72% of patients treated with mFOLFOX6 and 94% of patients treated with CAPOX (P = 0.13). CONCLUSION: This study can be verified the findings observed in our previous single-center study, oxaliplatin-based adjuvant chemotherapy was associated with an increase in SV. Furthermore, this increase can persist for > 1 year. The continuous presence of SOS may have a negative impact on prognosis in patients that develop recurrent disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Oxaliplatina/efeitos adversos , Esplenopatias/induzido quimicamente , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Japão , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/administração & dosagem , Prognóstico , Esplenopatias/diagnóstico por imagem
7.
JAMA Netw Open ; 3(7): e209486, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32633764

RESUMO

Importance: There is no proven test that can guide the optimal treatment, either endocrine therapy or chemotherapy, for estrogen receptor-positive breast cancer. Objective: To investigate the associations of sperm-associated antigen 5 (SPAG5) transcript and SPAG5 protein expressions with treatment response in systemic therapy for estrogen receptor-positive breast cancer. Design, Settings, and Participants: This retrospective cohort study included patients with estrogen receptor-positive breast cancer who received 5 years of adjuvant endocrine therapy with or without neoadjuvant anthracycline-based combination chemotherapy (NACT) derived from 11 cohorts from December 1, 1986, to November 28, 2019. The associations of SPAG5 transcript and SPAG5 protein expression with pathological complete response to NACT were evaluated, as was the association of SPAG5 mRNA expression with response to neoadjuvant endocrine therapy. The associations of distal relapse-free survival with SPAG5 transcript or SPAG5 protein expressions were analyzed. Data were analyzed from September 9, 2015, to November 28, 2019. Main Outcomes and Measures: The primary outcomes were breast cancer-specific survival, distal relapse-free survival, pathological complete response, and clinical response. Outcomes were examined using Kaplan-Meier, multivariable logistic, and Cox regression models. Results: This study included 12 720 women aged 24 to 78 years (mean [SD] age, 58.46 [12.45] years) with estrogen receptor-positive breast cancer, including 1073 women with SPAG5 transcript expression and 361 women with SPAG5 protein expression of locally advanced disease stage IIA through IIIC. Women with SPAG5 transcript and SPAG5 protein expressions achieved higher pathological complete response compared with those without SPAG5 transcript or SPAG5 protein expressions (transcript: odds ratio, 2.45 [95% CI, 1.71-3.51]; P < .001; protein: odds ratio, 7.32 [95% CI, 3.33-16.22]; P < .001). Adding adjuvant anthracycline chemotherapy to adjuvant endocrine therapy for SPAG5 mRNA expression in estrogen receptor-positive breast cancer was associated with prolonged 5-year distal relapse-free survival in patients without lymph node involvement (hazard ratio, 0.34 [95% CI, 0.14-0.87]; P = .03) and patients with lymph node involvement (hazard ratio, 0.35 [95% CI, 0.18-0.68]; P = .002) compared with receiving 5-year endocrine therapy alone. Mean (SD) SPAG5 transcript was found to be downregulated after 2 weeks of neoadjuvant endocrine therapy compared with pretreatment levels in 68 of 92 patients (74%) (0.23 [0.18] vs 0.34 [0.24]; P < .001). Conclusions and Relevance: These findings suggest that SPAG5 transcript and SPAG5 protein expressions could be used to guide the optimal therapies for estrogen receptor-positive breast cancer. Retrospective and prospective clinical trials are warranted.


Assuntos
Neoplasias da Mama , Proteínas de Ciclo Celular , Monitoramento de Medicamentos/métodos , Perfilação da Expressão Gênica/métodos , Receptores Estrogênicos/metabolismo , Antraciclinas/farmacologia , Antineoplásicos/farmacologia , Biomarcadores Farmacológicos/análise , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Resistencia a Medicamentos Antineoplásicos , Antagonistas do Receptor de Estrogênio/farmacologia , Moduladores de Receptor Estrogênico/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão
8.
Medicine (Baltimore) ; 99(29): e20443, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702809

RESUMO

BACKGROUND: Although common, the use of concurrent chemoradiotherapy with adjuvant chemotherapy for stage II nasopharyngeal carcinoma (NPC) is controversial due to its undefined clinical benefits. We, therefore, conducted a retrospective cohort study to investigate whether adjuvant chemotherapy confers survival gains to stage II NPC patients. METHODS: In this study, we examined whether combining adjuvant chemotherapy (AC) and/or concurrent chemotherapy with radiotherapy (CCRT) improved survival in patients with stage II NPC. Three hundred thirty-five stage II NPC patients were retrospectively analyzed between June 2003 and June 2016 and received CCRT; some patient groups also received AC every 3 weeks for 2 to 3 cycles. RESULTS: The median follow-up duration was 72 months for all patients (range, 26-151 months) and the estimated 5-year locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 95.1%, 97.8%, 93.5%, and 94.3%. At the last follow-up, there were no statistically significant differences among the CCRT and CCRT+AC groups in 5-year LRRFS (95.2% vs 94.9%, P = .599), DMFS (98.5% vs 92.4%, P = .152), PFS (93.8% vs 90.2%, P = .599), or OS (95.5% vs 93.9%, P = .682) rates. CONCLUSION: The analyses revealed that a combined regimen was not an independent prognostic factor for any survival outcome. However, patients who received CCRT plus AC experienced more acute adverse events than those who received CCRT alone. Thus, the addition of AC to CCRT did not improve survival outcomes, but was associated with higher incidences of acute treatment-associated toxicities than CCRT alone in patients with stage II NPC.


Assuntos
Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Estadiamento de Neoplasias , Prognóstico , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
9.
Lancet Oncol ; 21(8): 1110-1122, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702309

RESUMO

BACKGROUND: Outcomes for children and adults with advanced soft tissue sarcoma are poor with traditional therapy. We investigated whether the addition of pazopanib to preoperative chemoradiotherapy would improve pathological near complete response rate compared with chemoradiotherapy alone. METHODS: In this joint Children's Oncology Group and NRG Oncology multicentre, randomised, open-label, phase 2 trial, we enrolled eligible adults (aged ≥18 years) and children (aged between 2 and <18 years) from 57 hospitals in the USA and Canada with unresected, newly diagnosed trunk or extremity chemotherapy-sensitive soft tissue sarcoma, which were larger than 5 cm in diameter and of intermediate or high grade. Eligible patients had Lansky (if aged ≤16 years) or Karnofsky (if aged >16 years) performance status score of at least 70. Patients received ifosfamide (2·5 g/m2 per dose intravenously on days 1-3 with mesna) and doxorubicin (37·5 mg/m2 per dose intravenously on days 1-2) with 45 Gy preoperative radiotherapy, followed by surgical resection at week 13. Patients were randomly assigned (1:1) using a web-based system, in an unmasked manner, to receive oral pazopanib (if patients <18 years 350 mg/m2 once daily; if patients ≥18 years 600 mg once daily) or not (control group), with pazopanib not given immediately before or after surgery at week 13. The study projected 100 randomly assigned patients were needed to show an improvement in the number of participants with a 90% or higher pathological response at week 13 from 40% to 60%. Analysis was done per protocol. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02180867. FINDINGS: Between July 7, 2014, and Oct 1, 2018, 81 eligible patients were enrolled and randomly assigned to the pazopanib group (n=42) or the control group (n=39). At the planned second interim analysis with 42 evaluable patients and a median follow-up of 0·8 years (IQR 0·3-1·6) in the pazopanib group and 1 year (0·3-1·6) in the control group, the number of patients with a 90% pathological response or higher was 14 (58%) of 24 patients in the pazopanib group and four (22%) of 18 patients in the control group, with a between-group difference in the number of 90% or higher pathological response of 36·1% (83·8% CI 16·5-55·8). On the basis of an interim analysis significance level of 0·081 (overall one-sided significance level of 0·20, power of 0·80, and O'Brien-Fleming-type cumulative error spending function), the 83·8% CI for response difference was between 16·5% and 55·8% and thus excluded 0. The improvement in pathological response rate with the addition of pazopanib crossed the predetermined boundary and enrolment was stopped. The most common grade 3-4 adverse events were leukopenia (16 [43%] of 37 patients), neutropenia (15 [41%]), and febrile neutropenia (15 [41%]) in the pazopanib group, and neutropenia (three [9%] of 35 patients) and febrile neutropenia (three [9%]) in the control group. 22 (59%) of 37 patients in the pazopanib group had a pazopanib-related serious adverse event. Paediatric and adult patients had a similar number of grade 3 and 4 toxicity. There were seven deaths (three in the pazopanib group and four in the control group), none of which were treatment related. INTERPRETATION: In this presumed first prospective trial of soft tissue sarcoma spanning nearly the entire age spectrum, adding pazopanib to neoadjuvant chemoradiotherapy improved the rate of pathological near complete response, suggesting that this is a highly active and feasible combination in children and adults with advanced soft tissue sarcoma. The comparison of survival outcomes requires longer follow-up. FUNDING: National Institutes of Health, St Baldrick's Foundation, Seattle Children's Foundation.


Assuntos
Antineoplásicos/administração & dosagem , Quimiorradioterapia/métodos , Terapia Neoadjuvante/métodos , Pirimidinas/administração & dosagem , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Sulfonamidas/administração & dosagem , Adolescente , Adulto , Antineoplásicos/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Pirimidinas/efeitos adversos , Radioterapia Adjuvante , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/radioterapia , Sulfonamidas/efeitos adversos , Adulto Jovem
10.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(7): 657-660, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32683826

RESUMO

The standard treatment for advanced gastric cancer remains surgery-based comprehensive treatment. The D2 radical surgery has made outstanding contributions to the standarlization of gastric cancer surgery, which has improved patients' prognosis and quality of life. In recent years, neoadjuvant chemotherapy has achieved a certain effect on the treatment of advanced gastric cancer. With the continuous development of the concept of membrane anatomy in gastric cancer surgery, new surgical challenges have also been raised. For patients after neoadjuvant therapy, there is heated controversy in the possibility of completing radical gastrectomy with membrane anatomical concept for gastric cancer. We believe that if neoadjuvant therapy pushes mesenteric cancer cell back into the mesentery, theoretically membrane anatomy combined with neoadjuvant therapy is beneficial to the treatment efficacy of advanced gastric cancer. However, membrane anatomy has two important problems when combined with neoadjuvant therapy: (1) After neoadjuvant chemotherapy, there are varying degrees of edema around the stomach tissue, which will affect the visualization of anatomic planes. In addition, because the patients' coagulation function is damaged to a certain extent, it is difficult to avoid bleeding or minimize bleeding during the operation. Therefore, it is still controversial whether the patients with gastric cancer after neoadjuvant chemotherapy can undergo radical gastrectomy with membrane anatomy. (2) For patients with complete pathological remission, whether to obtain the maximum rate of pathological remission through intensive neoadjuvant therapy, or to obtain the survival benefit of patients with membrane anatomy surgery in clinic is still controversial. Faced with these confusions, multi-center clinical researches on the application of membrane anatomy surgery after neoadjuvant therapy is the only solution.


Assuntos
Gastrectomia/métodos , Mesentério/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Edema/etiologia , Gastrectomia/efeitos adversos , Humanos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Mesentério/anatomia & histologia , Mesentério/irrigação sanguínea , Mesentério/patologia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Prognóstico , Qualidade de Vida , Neoplasias Gástricas/patologia
11.
BMC Cancer ; 20(1): 498, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487091

RESUMO

BACKGROUND: Addition of oxaliplatin to capecitabine remains controversial for locally advanced rectal cancer (LARC). And cumulative oxaliplatin dose (COD) varied among clinical trials showing different therapeutic effects of this regimen. The objective of this study was to explore how COD affected tumor metastasis and patient survival. METHODS: Totally 388 patients diagnosed with stage cII-III rectal cancer and treated with neoadjuvant chemoradiotherapy followed by radical surgery plus adjuvant chemotherapy were consecutively enrolled into this study and retrospectively reviewed. After grouping by total chemotherapy cycle (TCC), influences of COD on adverse effects and patients' survivals were analyzed in each group. Univariate and multivariate survival analyses were performed through Kaplan-Meier approach and COX proportional hazards model, respectively. Age, gender, anemia, differentiation, carcinoembryonic antigen, carbohydrate antigen 19-9, pretreatment clinical stage and postsurgical pathologic stage were used as covariates. RESULTS: COD < 460 mg/m2 emerged as an independent predictor of poorer overall, metastasis-free and disease-free survivals, in patients treated with TCC ≤ 7. The hazard ratios were 1.972, 1.763 and 1.637 (P values were 0.021, 0.028 and 0.041), respectively. But it was note-worthy that COD ≥460 mg/m2 increased incidence of acute toxicities from 38.4 to 70.8% (P < 0.001). And in patients treated with TCC ≥ 8, COD failed to be a prognosticator. CONCLUSIONS: For LARC patients treated with insufficient TCC (≤ 7), oxaliplatin of ≥460 mg/m2 might be needed to improve survival, though it might resulted in more acute toxicities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Oxaliplatina/administração & dosagem , Neoplasias Retais/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Metástase Neoplásica/prevenção & controle , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Oxaliplatina/efeitos adversos , Fótons/uso terapêutico , Protectomia , Radioterapia Conformacional/métodos , Neoplasias Retais/patologia , Reto/efeitos dos fármacos , Reto/patologia , Reto/efeitos da radiação , Reto/cirurgia , Adulto Jovem
12.
Breast Cancer Res Treat ; 182(2): 259-266, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32488391

RESUMO

BACKGROUND: Adjuvant endocrine therapy is a gold standard in early-stage, hormone receptor positive breast cancer. In postmenopausal women, aromatase inhibitors (AIs) are associated with improved outcome compared to tamoxifen monotherapy. Differences in the toxicity profiles of these drugs are described; however, little is known about whether the risk of adverse events changes over time. METHODS: Sequential reports of large, randomized, adjuvant endocrine therapy trials comparing AIs to tamoxifen were reviewed. Data on pre-specified adverse events were extracted including cardiovascular events, bone fractures, cerebrovascular disease, endometrial cancer, secondary malignancies excluding breast cancer, venous thrombosis and death without recurrence. Odds ratios (ORs) were calculated for each adverse event at each time over the course of follow-up. The change in the ORs for adverse events over time was evaluated using weighted linear regression. RESULTS: Analysis included 21 reports of 7 trials comprising 30,039 patients and reporting outcomes between 28 and 128 months of follow-up. Compared to tamoxifen, AIs use was associated with a significant reduction in the magnitude of increased odds of bone fracture over time (ß = - 0.63, p = 0.013). There was a non-significant decrease in the magnitude of reduced odds of secondary malignancies over time (ß = 0.448, p = 0.094). The differences in other toxicity profiles between AIs and tamoxifen did not change significantly over time. CONCLUSIONS: The increased risk of bone fractures associated with adjuvant AIs falls over time and after discontinuation of treatment. Differences in other toxicities between AIs and tamoxifen do not change significantly over time including a persistently elevated risk of cardiovascular events.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/terapia , Doenças Cardiovasculares/epidemiologia , Fraturas Ósseas/epidemiologia , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/patologia , Doenças Cardiovasculares/induzido quimicamente , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Ensaios Clínicos Fase III como Assunto , Feminino , Fraturas Ósseas/induzido quimicamente , Humanos , Mastectomia , Estadiamento de Neoplasias , Pós-Menopausa , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Tamoxifeno/efeitos adversos , Resultado do Tratamento
13.
Int J Clin Oncol ; 25(10): 1807-1813, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32533352

RESUMO

BACKGROUND: A 4-week administration of tegafur/gimeracil/oteracil (S-1) followed by a 2-week rest is the standard adjuvant chemotherapy for surgically resected advanced gastric cancer. This study aimed to evaluate the oncological feasibility of a 2-week S-1 administration followed by a 1-week rest, which is frequently applied in clinical practice to reduce toxicity and improve drug adherence. METHODS: We retrospectively enrolled patients with stage II/III gastric cancer who received S-1 adjuvant chemotherapy following radical gastrectomy from 2006 to 2016 in three institutions. Two-week and 4-week regimen cohorts were compared for relative dose intensity (RDI) as a primary outcome, and treatment completion rate, adverse event incidence, overall survival (OS), and relapse-free survival (RFS) as secondary outcomes. Confounders were adjusted for using propensity score matching (PSM). RESULTS: One hundred and thirty-four patients received the 2-week regimen and 121 patients received the 4-week regimen. Ninety-five patients were extracted from each group after PSM. The RDIs of S-1 in the 2-week and 4-week cohorts were 73.5 and 69.9%, respectively (p = 0.35), which were not significantly different. The treatment completion rate (54.7 vs. 53.7%, p = 1.0), incidence of grade ≥3 adverse events (7.4 vs. 12.6%, p = 0.33), 3-year OS (76.4 vs. 82.7%, p = 0.78), and 3-year RFS (71.3 vs. 73.4%, p = 0.70) did not significantly differ between both cohorts. CONCLUSIONS: The 2-week S-1 adjuvant chemotherapy could not improve drug adherence in terms of RDI, but its relapse rates were not significantly different compared with those of the 4-week regimen. The 2-week regimen might be considered as an option depending on the patient's status.


Assuntos
Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Idoso , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Combinação de Medicamentos , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
14.
Sci Rep ; 10(1): 9710, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546796

RESUMO

Cardiorespiratory fitness is an independent risk factor for cardiovascular disease and shortened life expectancy in breast cancer survivors. This randomised controlled trial (n = 153) was designed for patients with a physically inactive lifestyle prediagnosis and concurrently referred to adjuvant chemotherapy. We compared two 12-week exercise interventions aimed at physiological and patient-reported outcomes (cardiorespiratory fitness, muscle strength, metabolic markers, physical activity, pain, fatigue), including a 39-week follow-up. A supervised hospital-based moderate to high intensity group exercise intervention was compared to an instructed home-based individual pedometer intervention. The two 12-week interventions included oncologists' recommendations and systematic health counselling. Outcomes were measured at baseline and week 6, 12 and 39. Primary outcome cardiorespiratory fitness declined significantly during chemotherapy and was restored in both interventions at follow-up. The interventions effectively engaged breast cancer patients in sustaining physical activities during and following adjuvant treatment. A composite metabolic score improved significantly. Positive cardiorespiratory fitness responders had improved clinical effects on fatigue, pain and dyspnoea versus negative responders. We conclude that a loss of cardiorespiratory fitness among physically inactive breast cancer patients may be restored by early initiated interventions and by adapting to physical activity recommendations, leading to a decreased cardiovascular risk profile in breast cancer survivors.


Assuntos
Terapia por Exercício/métodos , Fadiga/etiologia , Aptidão Física/fisiologia , Adjuvantes Imunológicos/uso terapêutico , Adjuvantes Farmacêuticos/efeitos adversos , Adjuvantes Farmacêuticos/uso terapêutico , Adulto , Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/fisiopatologia , Sobreviventes de Câncer , Aptidão Cardiorrespiratória/fisiologia , Quimioterapia Adjuvante/efeitos adversos , Exercício Físico/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Força Muscular/fisiologia , Aptidão Física/psicologia , Qualidade de Vida , Comportamento Sedentário
15.
Eur J Cancer ; 135: 78-88, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32554314

RESUMO

BACKGROUND: Immune-contexture of tumour microenvironment (TME) influences prognosis of colorectal cancer (CRC) patients and can be altered by cytotoxic and targeted agents. Limited data are available regarding the immune-TME of CRC after treatment. METHODS: An extensive immunohistochemistry evaluation of immunological parameters on tumour cells and TME of colorectal liver metastases from 106 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (5-fluorouracil, oxaliplatin and irinotecan) or COI (capecitabine, oxaliplatin and irinotecan) plus bevacizumab (N = 59) or cetuximab (N = 47) in five first-line no-profit clinical trials was performed. RESULTS: No substantial differences were reported in immunological parameters according to administered targeted agent, RAS/BRAF mutational status and histopathological or Response Evaluation Criteria in Solid Tumours response. Stromal expression of Cyclooxygenase-2 (COX-2) (p = 0.002), Human leukocyte antigen (HLA) (p = 0.003) and Programmed cell death protein 1 (PD1) (p = 0.002) were independent prognostic factors for longer relapse-free survival (RFS) at multivariate analysis with a positive trend for post-resection overall survival (OS). Patients whose metastases expressed stromal COX-2, HLA and PD1 (inflamed-score positive) reported longer RFS (25.5 versus 9.8 months; p < 0.001) and post-resection OS (64.3 versus 37.7 months; p = 0.003) as compared with others. In addition, patients with higher expression of CD4 and CD8 T-cells in tumour core and invasive margin (CD4/CD8-score) showed a better post-resection OS (not-reached versus 41.6 months; p = 0.032). A combined score of inflamed-score and CD4/CD8-score (combo-score) showed a clear prognostic role. CONCLUSIONS: The present study emphasises the role of immune-TME as independent predictor of survival in patients resected after triplets plus biologic. Inflamed-, CD4/C8- and combo-scores should be confirmed as prognostic factors in further studies.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/terapia , Linfócitos do Interstício Tumoral/imunologia , Terapia Neoadjuvante , Microambiente Tumoral/imunologia , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina/administração & dosagem , Cetuximab/administração & dosagem , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/mortalidade , Ensaios Clínicos como Assunto , Neoplasias Colorretais/mortalidade , Feminino , Fluoruracila/administração & dosagem , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina/administração & dosagem , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
16.
Breast Cancer Res Treat ; 182(2): 247-258, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32447595

RESUMO

PURPOSE: Older patients with early-stage breast cancer (ESBC) tend to receive less aggressive treatment, have higher mortality rates, and are underrepresented in clinical trials. Outcomes, tolerance and toxicity of chemotherapy are underreported. Thus, we assessed the outcomes of chemotherapy in the real-world in a community oncology setting. METHODS: We retrospectively chart reviewed consecutive older patients (≥ 70 years) with ESBC diagnosed between January 1, 2010, and December 31, 2016, who received chemotherapy at our institution. Study outcomes were survival estimates. Logistic regression determined associations with measures of intolerance. RESULTS: Of 1296 patients, 229 received chemotherapy. Overall, 24% had early chemotherapy cessation; 18% had dose reductions; and 27% had dose delays. Severe, life threatening and lethal toxicities occurred in 38%, 1.3%, and 2.2%, respectively; constitutional toxicity (37%) was the most common. The 1- and 3-year overall survivals were 94% and 79%; 1- and 3-year breast-specific survivals were 96% and 89%, while 1- and 3-year disease-free survivals were 95% and 82%, respectively. Anthracyclines were the most poorly tolerated regimen having associations with hospital visits (OR 10.97, 95% CI 2.10-57.23) and severe toxicities (OR 5.28, 95% CI 1.27-21.89). Anti-HER2 therapies (OR 3.03, 95% CI 1.18-7.78) and poorer performance status (PS) (OR 7.48, 95% CI 1.75-31.98) were associated with severe toxicities. Older age (> 80 years) was associated with early cessation of therapy (OR 3.64, 95% CI 1.34-9.83). CONCLUSIONS: Chemotherapy can be effectively delivered to older patients with ESBC and is reasonably well tolerated. The high rate of anthracycline intolerability, poorer PS, and advanced age should be considered when tailoring treatment regimens.


Assuntos
Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/terapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Mastectomia , Estadiamento de Neoplasias , Receptor ErbB-2/antagonistas & inibidores , Estudos Retrospectivos , Índice de Gravidade de Doença
17.
Breast Cancer Res Treat ; 182(2): 325-332, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32462261

RESUMO

BACKGROUND: Chemotherapy-induced amenorrhea (CIA) is one of the critical side effects from the chemotherapy in premenopausal patients with breast cancer. The goals of our study are the following: (1) to investigate the factors affecting the incidence of CIA; and (2) to evaluate the prognostic role of CIA in premenopausal patients with breast cancer. METHODS: We conducted a post hoc retrospective substudy to examine the incidence of the CIA and the relationship between CIA and prognosis in NSAS-BC02 that compared taxane alone to Doxorubicin(A) Cyclophosphamide(C) followed by taxane in postoperative patients with node-positive breast cancer RESULTS: Of 395 premenopausal women, 287 (72.7%) had CIA due to protocol treatment. Regarding type of protocol regimen, proportion of CIA was 76.9% in AC Paclitaxel(P), 75.2% in AC Docetaxel(D), 62.8% in PTX, and 75.2% in DTX. Predictive factors of CIA were age increase by 5 years (OR 1.50), ER positivity (OR 2.08), and HER2 3 + ( OR 0.40) according to logistic regression analysis. According to the log rank test and the Cox proportional hazards model, CIA group had significantly better disease-free survival than non-CIA group (P < .0001). However, according to time-dependent Cox model that was used to reduce guarantee-time bias, CIA was not a statistically significant prognostic factor in both ER-positive and ER-negative patients. CONCLUSION: Treatment with taxane alone caused high frequency of CIA in premenopausal women with breast cancer. CIA did not turn out to be an independent prognostic factor, taking guarantee-time bias into consideration. Further clinical studies are needed to validate these findings.


Assuntos
Amenorreia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/terapia , Metástase Linfática/terapia , Pré-Menopausa/efeitos dos fármacos , Adulto , Amenorreia/induzido quimicamente , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Feminino , Humanos , Incidência , Mastectomia , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Prognóstico , Estudos Prospectivos , Receptores Estrogênicos/metabolismo , Estudos Retrospectivos , Taxoides/efeitos adversos , Adulto Jovem
18.
Breast Cancer Res Treat ; 182(2): 333-343, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32468335

RESUMO

PURPOSE: Cardiotoxicities are adverse effects often reported in chemotherapy-treated breast cancer patients. This study evaluated the potential risk factors and cumulative incidence of doxorubicin-induced cardiotoxicity in Korean breast cancer patients. METHODS: We retrospectively analyzed the data of 613 breast cancer patients who underwent a multigated acquisition (MUGA) scan or echocardiography prior to chemotherapy and at least one post-chemotherapy follow-up MUGA scan/echocardiography between 2007 and 2016 at National Cancer Center, Korea. The Cox proportional hazards models were used to evaluate cardiotoxicity risks. Competing risks analyses were performed to estimate cumulative incidence of cardiotoxicity. RESULTS: Risk factors associated with cardiotoxicity within 2 years of doxorubicin administration included age [adjusted hazard ratio (aHR) = 1.02, 95% confidence interval (CI) 1.00-1.04; p = 0.05], metastasis (aHR = 2.66; 95% CI 1.36-5.20; p < 0.01), and concomitant trastuzumab (aHR = 4.08; 95% CI 2.31-7.21; p < 0.01). The cumulative incidence of patients with cardiotoxicity was 6.1% at 2 years (without substantial change from about 9 months)and 20.2% at 2 years (without substantial change from about 15 months) after initiation of doxorubicin-containing therapy without and with trastuzumab, respectively. CONCLUSIONS: Susceptibility to chemotherapy-induced cardiotoxicity within 2 years of doxorubicin initiation in breast cancer patients was elevated with old age, metastasis, and concomitant trastuzumab. Regular imaging monitoring at least up to 9 months after doxorubicin initiation in patients treated without concomitant trastuzumab, and 15 months in patients treated with concomitant trastuzumab, is needed for early detection of chemotherapy-induced cardiotoxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/terapia , Cardiotoxicidade/epidemiologia , Doxorrubicina/efeitos adversos , Trastuzumab/efeitos adversos , Adulto , Idoso , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/etiologia , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Relação Dose-Resposta a Droga , Ecocardiografia , Feminino , Seguimentos , Humanos , Incidência , Mastectomia , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco
19.
BMC Cancer ; 20(1): 485, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32471382

RESUMO

BACKGROUND: Preoperative radiochemotherapy (RCT) is recommended in France prior to total mesorectal excision in patients with mid or low locally advanced rectal cancer (LARC) (cT3/T4 and/or N+) because it has been shown to improve local control. Preoperative RCT has also disadvantages including the absence of proven impact on metastatic recurrence and the risk of late side effects on bowel and genitourinary function. In patients with primarily resectable LARC, preoperative systemic chemotherapy without pelvic irradiation could be used as an alternative to RCT. METHODS: This study is a multicenter, open-label randomized, 2-arm phase III non-inferiority trial. Patients with mid or low resectable LARC (cT3N0 or cT1-T3N+ with circumferential resection margin [CRM] > 2 mm on pretreatment MRI) will be randomized to either modified FOLFIRINOX for 3 months or RCT (Cap50 intensified-modulated radiotherapy). All patients have restaging MRI after preoperative treatment. The primary endpoint is 3-year progression-free survival (PFS) from the time to randomization including progression during preoperative treatment. Secondary endpoints are treatment related toxicity, treatment compliance, R0 resection rate, sphincter saving surgery rate, postoperative morbidity and mortality rates, loco-regional recurrence free survival, overall survival, bowel and sexual functions at diagnosis, quality of life, radiologic and pathologic response after preoperative treatment. The number of patients required is 574. DISCUSSION: The choice of modified FOLFIRINOX for preoperative chemotherapy is supported by recent and consistent data on safety and efficacy of this regimen on rectal cancer. The use of preoperative chemotherapy instead of RCT could be associated with pronounced advantages in terms of functional results and quality of life in cancer survivors. However and first of all, the non-inferiority of preoperative chemotherapy compared to RCT on oncologic outcome has to be validated. If this study demonstrates the non-inferiority of chemotherapy compared to RCT, this can lead to a crucial change in clinical practice in a large subset of rectal cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03875781 (March 15, 2019). Version 1.1.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Neoadjuvante/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia Adjuvante/estatística & dados numéricos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Esquema de Medicação , Estudos de Equivalência como Asunto , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Cooperação do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Período Pré-Operatório , Protectomia/efeitos adversos , Intervalo Livre de Progressão , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Reto/efeitos dos fármacos , Reto/patologia , Reto/efeitos da radiação , Reto/cirurgia
20.
J Surg Res ; 253: 262-271, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32388389

RESUMO

BACKGROUND: Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be beneficial in treating limited peritoneal carcinomatosis (PC) from colorectal cancer (CRC). Perfusate volume directly affects treatment concentration and therefore is a key parameter defining HIPEC; yet little is known about the impact of perfusate concentration on systemic toxicity and treatment morbidity. MATERIALS AND METHODS: PC was induced through intraperitoneal injection of human CRC cell lines. A novel perfusion model was developed to treat athymic nude mice with continuous circulation of adequately miniaturized volumes of heated perfusate. Oxaliplatin HIPEC was performed applying different volumes of perfusate with fixed doses or fixed concentrations. Early postoperative mortality and morbidity were assessed as well as long-term survival. In addition, antiproliferative and proapoptotic effects of HIPEC were determined in vitro and in vivo. RESULTS: Perfusate concentration crucially affected the toxicity of fixed-dose oxaliplatin HIPEC as indicated by postoperative weight loss and early postoperative mortality. Applying different perfusate volumes at a fixed concentration did not influence toxicity. Adequately miniaturized HIPEC with oxaliplatin did not exert relevant cytotoxic effects toward PC arising from human CRC cells in vivo. CONCLUSIONS: We describe a novel murine model that adequately miniaturizes all physical parameters of HIPEC as applied in humans. HIPEC drug concentration is a crucial parameter determining excess toxicity and should be better standardized. HIPEC with oxaliplatin fails to induce relevant antitumor activity or to improve survival in this murine model of PC from CRC.


Assuntos
Quimioterapia do Câncer por Perfusão Regional/métodos , Neoplasias Colorretais/patologia , Hipertermia Induzida/métodos , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/terapia , Animais , Linhagem Celular Tumoral , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Procedimentos Cirúrgicos de Citorredução , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Camundongos , Oxaliplatina/toxicidade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Peritônio/efeitos dos fármacos , Peritônio/patologia , Falha de Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
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