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1.
Oncologist ; 27(10): e811-e814, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35946834

RESUMO

Physical activity (PA) is associated with improvement in breast cancer treatment-related symptoms and survival, yet most breast cancer survivors do not meet national PA guidelines. This study aimed to identify characteristics of participants that were associated with an increased likelihood of meeting PA guidelines. Adults with breast cancer seen at Mayo Clinic (Rochester, MN) were surveyed regarding their PA participation, and those who self-reported at least 150 minutes of moderate and/or strenuous aerobic PA weekly on average were considered to be "meeting guidelines". Three thousand participants returned PA data. Younger age, completion of the survey 7-12 years after diagnosis, absence of recurrence, no bilateral mastectomy, absence of metastatic disease, and lower BMI at the time of survey completion were associated with PA participation (P < .05 in univariate and multivariate analyses). Findings were similar when a threshold of 90 minutes was applied. These results may inform the development of targeted PA-facilitating interventions.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Adulto , Neoplasias da Mama/terapia , Exercício Físico , Feminino , Humanos , Mastectomia , Sobreviventes
2.
Support Care Cancer ; 31(1): 40, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36525104

RESUMO

PURPOSE: This project evaluated the dietary supplement (DS) use of patients referred to an integrative oncology program and documented the frequency and reasons for recommending stopping DS. Many patients with cancer are taking dietary supplements and may not disclose such to their care teams. There is potential for harm in several ways: (1) interactions with their medications that may increase side effects, (2) interactions with their treatment that may lead to decreased efficacy, and 3) direct toxicity from the supplement. METHODS: Patient data (N = 100) were collected prospectively from an Integrative Oncology Clinic. The number and type of DS were documented. Using the Natural Medicines Database, we determined whether supplements interacted with the patient's other medications or cancer therapies. We calculated the percentage of patients in which a recommendation for discontinuation (DC) of DS was provided, along with the supporting reasons. RESULTS: We found that 91% of patients took DS, averaging 5.5 per patient (range 0-20). In 35% of patients, we recommended stopping some of their DS or other therapies, the reasons being: DC antioxidants, vitamin B12/iron while on chemo/RT (unless deficient or part of protocol) 32%; DC due to taking excess amounts (i.e., fat-soluble vitamins, calcium, iron) 13.5%; DC supplements with known toxicity (i.e., laetrile, Miracle mineral solution) 13.5%; DC due to interactions with other medications (i.e., anticoagulants) 13.5%; DC DS with potential to increase cancer growth (i.e., estrogenic potential in those with hormone-sensitive cancers, glutamine) 11%; DC due to potential for increased toxicity with chemotherapy (i.e., increased risk of bleeding, CIPN) 11%; DC probiotics, immune stimulants, and cannabis while on immunotherapy 5.4%. CONCLUSIONS: Patients with cancer referred to an integrative oncology clinic use large numbers of DS with the potential for adverse effects and/or decreasing efficacy of treatments. This study highlights the prevalence of DS usage in cancer patients referred to an integrative oncology clinic and demonstrates the need for counseling about safe supplement use.


Assuntos
Oncologia Integrativa , Neoplasias , Humanos , Suplementos Nutricionais , Vitaminas/efeitos adversos , Ferro , Neoplasias/tratamento farmacológico
3.
J Transl Med ; 16(1): 142, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29843811

RESUMO

BACKGROUND: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma. METHODS: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). RESULTS: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. CONCLUSIONS: Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival. Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1 ; initially registered 19 September 2002.


Assuntos
Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Glioblastoma/imunologia , Glioblastoma/terapia , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico , Vacinas Anticâncer/efeitos adversos , Determinação de Ponto Final , Feminino , Glioblastoma/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
4.
J Transl Med ; 16(1): 179, 2018 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-29958537

RESUMO

Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section.

5.
Obes Pillars ; 10: 100106, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38495815

RESUMO

Background: The link between excess adiposity and carcinogenesis has been well established for multiple malignancies, and cancer is one of the main contributors to obesity-related mortality. The potential role of different weight-loss interventions on cancer risk modification has been assessed, however, its clinical implications remain to be determined. In this clinical review, we present the data assessing the effect of weight loss interventions on cancer risk. Methods: In this clinical review, we conducted a comprehensive search of relevant literature using MEDLINE, Embase, Web of Science, and Google Scholar databases for relevant studies from inception to January 20, 2024. In this clinical review, we present systematic reviews and meta-analysis, randomized clinical trials, and prospective and retrospective observational studies that address the effect of different treatment modalities for obesity in cancer risk. In addition, we incorporate the opinions from experts in the field of obesity medicine and oncology regarding the potential of weight loss as a preventative intervention for cancer. Results: Intentional weight loss achieved through different modalities has been associated with a reduced cancer incidence. To date, the effect of weight loss on the postmenopausal women population has been more widely studied, with multiple reports indicating a protective effect of weight loss on hormone-dependent malignancies. The effect of bariatric interventions as a protective intervention for cancer has been studied extensively, showing a significant reduction in cancer incidence and mortality, however, data for the effect of bariatric surgery on certain specific types of cancer is conflicting or limited. Conclusion: Medical nutrition therapy, exercise, antiobesity medication, and bariatric interventions, might lead to a reduction in cancer risk through weight loss-dependent and independent factors. Further evidence is needed to better determine which population might benefit the most, and the amount of weight loss required to provide a clinically significant preventative effect.

6.
Artigo em Inglês | MEDLINE | ID: mdl-39016024

RESUMO

Background: Patients have been known to use cannabinoids for treating established chemotherapy-induced peripheral neuropathy (CIPN) based on anecdotal information and retrospective reports suggesting that such might be beneficial. In response, a double-blinded, placebo-controlled, randomized, pilot clinical trial was developed to evaluate whether resultant data would support a phase III trial for testing whether a cannabidiol (CBD) cream might improve CIPN. Methods: Forty patients with established CIPN were randomized, in a double-blinded manner, to topical CBD or a placebo cream. The study product was applied for 2 weeks, followed by a crossover for 2 weeks. Neuropathy was evaluated using the European Organization of Research and Treatment of Cancer (EORTC)-CIPN20, the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool, and the Global Impression of Change instruments. Side effects were recorded by symptom diaries. Results: The EORTC-CIPN20 scores were similar in the patients receiving CBD versus the placebo. Likewise, the toxicity scores were similar in patients who received the CBD versus the placebo. Conclusions: This pilot trial did not support that the studied CBD isolate cream improved painful established CIPN. It was well tolerated overall. Clinical Trial Registration Number: NCT05388058.

7.
Cancers (Basel) ; 16(14)2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39061134

RESUMO

BACKGROUND: There are limited evidence-based data to guide treatment recommendations for breast cancer (BC) patients ≥80 years (P80+). Identifying and addressing unmet needs are critical. AIMS: Advocate-BREAST80+ compared the needs of P80+ vs. patients < 80 years (P80-). METHODS: In 12/2021, a REDCap survey was electronically circulated to 6918 persons enrolled in the Mayo Clinic Breast Disease Registry. The survey asked about concerns and satisfaction with multiple aspects of BC care. RESULTS: Overall, 2437 participants responded (35% response rate); 202 (8.3%) were P80+. P80+ were less likely to undergo local regional and systemic therapies vs. P80- (p < 0.01). Notably, P80+ were significantly less satisfied with information about the short and long-term side effects of BC therapies and managing toxicities. P80+ were also less likely to have participated in a clinical trial (p < 0.001) or to want to do so in the future (p = 0.0001). CONCLUSIONS: Although P80+ experienced less anxiety and symptom-related distress compared with P80-, they were significantly less satisfied with information regarding the side effects of BC therapies and their management. P80+ were significantly less likely to have participated in a clinical trial or be open to considering this option. Future studies should address educational needs pertaining to side effects and barriers to research participation in P80+.

8.
BMJ ; 382: e071565, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37722731

RESUMO

Breast cancer survivors may experience significant after effects from diagnoses of breast cancer and cancer directed therapies. This review synthesizes the evidence about optimal management of the sequelae of a diagnosis of breast cancer. It describes the side effects of chemotherapy and endocrine therapy and evidence based strategies for management of such effects, with particular attention to effects of therapies with curative intent. It includes strategies to promote health and wellness among breast cancer survivors, along with data to support the use of integrative oncology strategies. In addition, this review examines models of survivorship care and ways in which digital tools may facilitate communication between clinicians and patients. The strategies outlined in this review are paramount to supporting breast cancer survivors' quality of life.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Humanos , Feminino , Neoplasias da Mama/terapia , Promoção da Saúde , Qualidade de Vida , Mama
9.
JNCI Cancer Spectr ; 7(5)2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37561108

RESUMO

BACKGROUND: Physical activity is associated with decreased breast cancer recurrence and mortality, as well as fewer treatment-related symptoms. Nevertheless, most breast cancer survivors do not meet physical activity guidelines. The purpose of this manuscript is to characterize physical activity trends over time in breast cancer survivors. METHODS: Mayo Clinic Breast Disease Registry participants received surveys at baseline and at 1 and 4 years after diagnosis; breast cancer recurrence and/or metastatic disease were exclusion criteria. Participants were considered to be meeting guidelines if they self-reported at least 150 minutes of moderate-intensity (eg, fast walking) and/or strenuous (eg, jogging) physical activity per week. Statistical analyses include analysis of covariance methods, paired t tests, conditional logistic regression models, and McNemar tests of homogeneity. RESULTS: A total of 171 participants were included in the analysis. The amount of total physical activity decreased over time (P = .07). Mild-intensity physical activity (eg, easy walking) decreased most over time (P = .05). Among participants aged 18-49 years, mild-intensity (P = .05) and moderate-intensity (P = .02) physical activity decreased over time. Strenuous-intensity physical activity levels decreased over time among participants with a normal body mass index (P = .002) and with obesity (P = .01). CONCLUSIONS: We found a trend-level decrease in total physical activity over time, driven mostly by a decrease in mild-intensity physical activity. Young breast cancer survivors are especially likely to reduce their physical activity over time. Further research on implementing physical activity guidelines in clinical practice is warranted.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Humanos , Feminino , Neoplasias da Mama/terapia , Exercício Físico , Sobreviventes , Inquéritos e Questionários
10.
JAMA Oncol ; 9(1): 112-121, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36394838

RESUMO

Importance: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed. Objective: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma. Design, Setting, and Participants: This phase 3, prospective, externally controlled nonrandomized trial compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC vs contemporaneous matched external control patients treated with SOC. This international, multicenter trial was conducted at 94 sites in 4 countries from August 2007 to November 2015. Data analysis was conducted from October 2020 to September 2021. Interventions: The active treatment was DCVax-L plus SOC temozolomide. The nGBM external control patients received SOC temozolomide and placebo; the rGBM external controls received approved rGBM therapies. Main Outcomes and Measures: The primary and secondary end points compared overall survival (OS) in nGBM and rGBM, respectively, with contemporaneous matched external control populations from the control groups of other formal randomized clinical trials. Results: A total of 331 patients were enrolled in the trial, with 232 randomized to the DCVax-L group and 99 to the placebo group. Median OS (mOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 (95% CI, 17.5-21.3) months from randomization (22.4 months from surgery) vs 16.5 (95% CI, 16.0-17.5) months from randomization in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months from randomization was 15.7% vs 9.9%, and at 60 months, it was 13.0% vs 5.7%. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 (95% CI, 9.7-16.8) months from relapse vs 7.8 (95% CI, 7.2-8.2) months among control patients (HR, 0.58; 98% CI, 0.00-0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively. Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P = .03). Conclusions and Relevance: In this study, adding DCVax-L to SOC resulted in clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received SOC alone. Trial Registration: ClinicalTrials.gov Identifier: NCT00045968.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Temozolomida/uso terapêutico , Estudos Prospectivos , Neoplasias Encefálicas/patologia , Recidiva , Células Dendríticas/patologia , Vacinação
11.
JCO Precis Oncol ; 6: e2200306, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36315917

RESUMO

PURPOSE: The TAPUR Study is a pragmatic phase II basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from two cohorts of patients with colorectal cancer (CRC) with either ERBB2 amplifications or ERBB2 or ERBB3 (ERBB2/3) mutations treated with pertuzumab plus trastuzumab (P + T) are reported. METHODS: Eligible patients with measurable CRC were selected for treatment with P + T according to protocol-specified genomic matching rules. Patients had no remaining standard treatment options, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. Simon's two-stage design was used with a primary study end point of disease control (DC; objective response [OR] or stable disease of at least 16 weeks duration [SD16+]). Secondary end points include safety, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS: Thirty-eight patients with CRC with ERBB2 amplification (N = 28) or ERBB2/3 mutations (N = 10) were treated with P + T. For the ERBB2 amplification cohort, DC and OR were observed in 54% and 25% of patients, respectively; the median PFS and median OS (95% CIs) were 17.2 (11.1 to 27.4) weeks and 60.0 (32.1 to 102.3) weeks, respectively. For the ERBB2/3 mutation cohort, DC and OR were observed in 10% and 0% of patients, respectively; the median PFS and median OS were 9.6 (5.1 to 16.0) weeks and 28.8 (7.6 to 146.3) weeks, respectively. Four of 38 patients experienced grade 3 adverse events or serious adverse events including anemia, infusion reaction, diarrhea, left ventricular systolic dysfunction, and decreased lymphocyte count. CONCLUSION: Although P + T treatment does not appear to have antitumor activity in CRC with ERBB2/3 mutations, this combination has antitumor activity in patients with CRC with ERBB2 amplification and warrants further study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Mutação , Receptor ErbB-2/genética , Trastuzumab/uso terapêutico
12.
J Clin Oncol ; 40(19): 2138-2147, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35290101

RESUMO

PURPOSE: Platinum-based chemotherapy is the standard of care for platinum-sensitive ovarian cancer, but complications from repeated platinum therapy occur. We assessed the activity of two all-oral nonplatinum alternatives, olaparib or olaparib/cediranib, versus platinum-based chemotherapy. PATIENTS AND METHODS: NRG-GY004 is an open-label, randomized, phase III trial conducted in the United States and Canada. Eligible patients had high-grade serous or endometrioid platinum-sensitive ovarian cancer. Patients were randomly assigned 1:1:1 to platinum-based chemotherapy, olaparib, or olaparib/cediranib. The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included activity within germline BRCA-mutated or wild-type subgroups and patient-reported outcomes (PROs). RESULTS: Between February 04, 2016, and November 13, 2017, 565 eligible patients were randomly assigned. Median PFS was 10.3 (95% CI, 8.7 to 11.2), 8.2 (95% CI, 6.6 to 8.7), and 10.4 (95% CI, 8.5 to 12.5) months with chemotherapy, olaparib, and olaparib/cediranib, respectively. Olaparib/cediranib did not improve PFS versus chemotherapy (hazard ratio [HR] 0.86; 95% CI, 0.66 to 1.10; P = .077). In women with germline BRCA mutation, the PFS HR versus chemotherapy was 0.55 (95% CI, 0.32 to 0.94) for olaparib/cediranib and 0.63 (95% CI, 0.37 to 1.07) for olaparib. In women without a germline BRCA mutation, the PFS HR versus chemotherapy was 0.97 (95% CI, 0.73 to 1.30) for olaparib/cediranib and 1.41 (95% CI, 1.07 to 1.86) for olaparib. Hematologic adverse events occurred more commonly with chemotherapy; however, nonhematologic adverse events were higher with olaparib/cediranib. In 489 patients evaluable for PROs, patients receiving olaparib/cediranib scored on average 1.1 points worse on the NFOSI-DRS-P subscale (97.5% CI, -2.0 to -0.2, P = .0063) versus chemotherapy; no difference between olaparib and chemotherapy was observed. CONCLUSION: Combination olaparib/cediranib did not improve PFS compared with chemotherapy and resulted in reduced PROs. Notably, in patients with a germline BRCA mutation, both olaparib and olaparib/cediranib had significant clinical activity.


Assuntos
Neoplasias Ovarianas , Platina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Indóis , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Ftalazinas/efeitos adversos , Piperazinas , Platina/uso terapêutico , Quinazolinas
13.
Integr Cancer Ther ; 20: 15347354211061739, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34841942

RESUMO

BACKGROUND: Chemotherapy-induced peripheral neuropathy is a common and often severe side effect from many chemotherapeutic agents, with limited treatment options. There is no literature on the use of topical cannabinoids for chemotherapy-induced neuropathy. CASE PRESENTATIONS: The current manuscript presents a case series of patients presenting in oncology clinics at Sutter Health, CA and Mayo Clinic, Rochester, MN from April 2019 to December 2020 with chemotherapy-induced peripheral neuropathy who used topical creams containing the cannabinoids delta-nine-tetrahydrocannabinol (THC) and/or cannabidiol (CBD). CONCLUSIONS: This case series suggests that topical cannabinoids may be helpful for patients with chemotherapy-induced peripheral neuropathy. This paper also discusses the potential mechanisms of action by which topical cannabinoids might alleviate established CIPN symptoms. A randomized placebo-controlled trial using a standardized product is planned to study the actual efficacy of such treatment.


Assuntos
Antineoplásicos , Canabidiol , Canabinoides , Doenças do Sistema Nervoso Periférico , Antineoplásicos/efeitos adversos , Dronabinol , Humanos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico
14.
Clin Colorectal Cancer ; 4(5): 325-31, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15663836

RESUMO

Although 5-fluorouracil (5-FU)-based chemotherapy is commonly used in patients with advanced colorectal cancer (CRC), little data exist on the tolerability and benefit of therapy in elderly patients. To compare toxicity, dose intensity, response rate, time to tumor progression, and overall survival for older and younger patients, we conducted a pooled analysis of 1748 patients, divided into 4 quartile-based age groups, from 4 North Central Cancer Treatment Group trials testing 5-FU with or without leucovorin for advanced CRC. Patients aged > 65 years had modestly higher rates of severe toxicity (grade >/= 3) overall (53% vs. 46%) and higher rates of diarrhea (21% vs. 16%), stomatitis (17% vs. 13%), and infection (4% vs. 2%). Toxicity rates were similar between patients aged 66-70 years and patients aged > 70 years. The response rate did not differ by age group (2-sided; P = 0.90); it was significantly lower for patients with higher performance status scores (30% for score of 0/1; 17% for 2/3; 2-sided; P = 0.001). Performance status, not age, was predictive of time to tumor progression and overall survival. The older patients with CRC treated with 5-FU have modestly higher rates of severe toxicity, mainly diarrhea and stomatitis. Supportive measures to control diarrhea and stomatitis may be particularly important in elderly patients. Age alone should not be used to determine whether older patients are treated, because performance status is predictive of dose intensity, response rate, time to tumor progression, and overall survival.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Distribuição de Qui-Quadrado , Ensaios Clínicos como Assunto , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do Tratamento
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