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2.
Radiother Oncol ; 196: 110219, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38479443

RESUMO

PURPOSE: We report the impact of 1 vs. 2 doses of mitomycin-C (MMC) based chemoradiation (CRT) on patterns of treatment failure and long-term patient outcomes in anal squamous cell carcinoma (ASCC) and the predictors for locoregional failure (LRF) and distant metastasis (DM). METHODS: In this population-based study, we identified all patients with anal cancer in our province treated radically with radiation and concurrent 5-Fluorouracil (5FU) and 1 vs. 2 doses of MMC between the years 2000-2019. The primary outcomes analyzed were locoregional recurrence (LRR), disease free survival (DFS), ASCC cancer-specific survival (ASCC-CSS) and overall survival (OS). RESULTS: 451 patients were identified. 272 (60%) patients received 1 cycle of MMC (MMC1) and 179 (40%) received 2 cycles (MMC2) as part of the CRT regimen. The median follow-up was 57 (36-252) and 97 (38-239) months for MMC1 and MMC2, respectively. Cox Regression analysis showed stage IIIb and IIIc were associated with worse locoregional recurrence free survival (RFS) (HR=2.851, p=<0.001) and distant RFS (HR=3.391, p=<0.001). Similarly, stage IIIb and IIIc patients had poorer DFS (HR 3.439, p=<0.001), ASCC-SS (HR 3.729, p=<0.001) and OS (2.230, p=<0.001). The use of MMC2 showed a positive impact on improved ASCC-SS (HR 0.569, p=0.029) and distant RFS (HR 0.555, p=0.040) in patients with stage IIIb and IIIc. CONCLUSIONS: Our analysis showed that 1 vs. 2 cycles of MMC along with 5FU and radiation is associated with comparable treatment outcomes in general. However, in patients with stage IIIb and IIIc cancer, 2 doses of MMC were associated with improved ASCC-SS and distant DFS.


Assuntos
Neoplasias do Ânus , Quimiorradioterapia , Fluoruracila , Mitomicina , Recidiva Local de Neoplasia , Humanos , Mitomicina/administração & dosagem , Mitomicina/uso terapêutico , Masculino , Feminino , Neoplasias do Ânus/terapia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/mortalidade , Quimiorradioterapia/métodos , Pessoa de Meia-Idade , Idoso , Fluoruracila/administração & dosagem , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/tratamento farmacológico , Falha de Tratamento , Adulto , Antibióticos Antineoplásicos/uso terapêutico , Antibióticos Antineoplásicos/administração & dosagem , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Intervalo Livre de Doença
3.
Int J Radiat Oncol Biol Phys ; 117(2): 434-445, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37148982

RESUMO

PURPOSE: Intensity modulated radiation therapy (IMRT) has confirmed its superiority in improving acute treatment-related toxicities in anal cancer, without compromising tumor control. However, the effect of IMRT on long-term quality of life (QOL) is poorly documented. The study prospectively evaluated the long-term patient-reported QOL after IMRT-based chemoradiation in anal cancer. METHODS AND MATERIALS: Fifty-eight patients treated with IMRT and concurrent 5 fluorouracil/mitomycin-C were enrolled in the study. A prespecified secondary endpoint was prospective evaluation of long-term QOL. Fifty-four patients underwent QOL evaluation at baseline, after treatment, and during follow-up until 60 months, with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) scales and the Colorectal Cancer-Specific Quality Of Life Questionnaire (QLQ-CR29) scales. The QOL scores at baseline and posttreatment periods were compared. RESULTS: For QLQ-C30, at 60 months, the mean scores of global health status, all functional scales, and all symptoms except diarrhea had improved, indicating normalization of QOL. Clinically and statistically significant improvements in the global health status (15.4; P = .003), role functioning (19.3; P = .0017), emotional functioning (18.9; P = .008), and social functioning (29.8; P ≤ .001) were observed. Diarrhea persisted as a concern over the years (P = .172). For European Organization for Research and Treatment of Cancer QLQ-CR29, rectal pain (-38.6; P = .001), mucous or blood discharge per rectum (-22.8; P = .005), and perianal soreness (-37.3; P ≤ .001) were improved both clinically and statistically. Clinically significant fecal leakage was reported by 16% of patients (5.6; P = .421). Volumes receiving 45 and 54 Gy were independent predictors for fecal incontinence. Clinically and statistically significant urinary incontinence occurred in 21% of patients (17.5; P = .014). Deterioration of dyspareunia was clinically significant (26.7; P = .099) at 60 months. CONCLUSIONS: Compared with historical data, IMRT is associated with reduced long-term effects on QOL. The majority of patients treated with IMRT experienced clinically significant recovery of function and improvement in QOL over 5 years after completion of treatment. Specific toxicities such as chronic diarrhea, fecal incontinence, and urinary and sexual dysfunction were primarily responsible for deterioration of the long-term QOL. Future research aimed at reducing such toxicities is needed to further improve long-term QOL in anal cancer.


Assuntos
Neoplasias do Ânus , Sobreviventes de Câncer , Incontinência Fecal , Radioterapia de Intensidade Modulada , Feminino , Humanos , Qualidade de Vida , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Incontinência Fecal/etiologia , Neoplasias do Ânus/terapia , Diarreia/etiologia , Medidas de Resultados Relatados pelo Paciente
4.
BMC Cancer ; 22(1): 1119, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319973

RESUMO

BACKGROUND: Colorectal cancer remains the second leading cause of cancer death in North America. Fluorouracil and oxaliplatin based adjuvant chemotherapy for resected colon cancer (CC) reduces cancer recurrence, but also causes significant toxicity requiring dose reductions. The effect of dose intensity on survival outcomes is not fully understood and strengthening the evidence supports informed decision making between patients and oncologists. METHODS: Patients treated with adjuvant chemotherapy, between 2006 and 2011, for resected colon cancer at four Canadian academic cancer centers were retrospectively analyzed. All patients must have received oxaliplatin with either capecitabine (CAPOX) or 5-FU (FOLFOX). Dose intensity (DI) was calculated as total delivered dose of an individual chemotherapy agent divided by the cumulative intended dose of that agent. The influence of DI on overall survival was examined. RESULTS: Five hundred thirty-one patients with high-risk stage II or stage III resected CC were eligible and included in the analysis. FOLFOX was the most common regimen (69.6%) with 29.7% of patients receiving CAPOX and 0.7% receiving both therapies. Median follow-up was 36.7 months. The median DI for 5-FU and capecitabine was 100% and 100% with 13.6% and 9.8% of patients receiving ≤ 80% DI, respectively. The median DI of oxaliplatin was 70% with 56.8% of patients receiving ≤ 80% DI. A DI of > 80% for each chemotherapy component was associated with a significant improvement in overall survival compared to those with a DI of ≤ 80% (5-FU HR = 0.23, 95% CI = 0.08-0.65, p = 0.006; capecitabine HR = 0.56, 95% CI = 0.33-0.94, p = 0.026; oxaliplatin HR = 0.52, 95% CI = 0.33-0.82, p = 0.005). Patients with T2 and/or N2 disease with an oxaliplatin DI > 80% had a trend towards improved survival (HR = 0.62, 95% CI = 0.38-1.02, p = 0.06). CONCLUSIONS: In resected CC an adjuvant chemotherapy DI of > 80%, of each chemotherapy agent, is associated with improved overall survival.


Assuntos
Neoplasias do Colo , Neoplasias Testiculares , Masculino , Humanos , Capecitabina , Oxaliplatina , Leucovorina , Estudos Retrospectivos , Compostos Organoplatínicos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Canadá , Quimioterapia Adjuvante/efeitos adversos , Neoplasias do Colo/patologia , Fluoruracila , Neoplasias Testiculares/tratamento farmacológico
5.
Curr Oncol ; 29(5): 3160-3170, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35621647

RESUMO

Gastric, esophageal and gastro-esophageal junction cancers are associated with inferior outcomes. For early-stage disease, perioperative chemotherapy or chemoradiation followed by surgery is the standard treatment. For most patients with advanced upper gastrointestinal tract cancers, platinum-based chemotherapy remains a standard treatment. Recently, several randomized clinical trials have demonstrated the benefit of immunotherapy involving checkpoint inhibitors alone or in combination with chemotherapy in patients with gastro-esophageal cancer and have changed the treatment landscape. The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC), involving experts from four Western Canadian provinces, convened virtually on 16 June 2021 and developed the recommendations on the role of immunotherapy in patients with gastro-esophageal cancer.


Assuntos
Neoplasias Esofágicas , Neoplasias Gastrointestinais , Neoplasias Gástricas , Canadá , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica , Neoplasias Gastrointestinais/terapia , Humanos , Imunoterapia , Neoplasias Gástricas/cirurgia
6.
Curr Oncol ; 29(3): 1796-1807, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35323347

RESUMO

The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) convened virtually on 4 November 2021. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals, including surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals from across four Western Canadian provinces, British Columbia, Alberta, Saskatchewan, and Manitoba, who are involved in the care of patients with gastrointestinal cancer. They participated in presentation and discussion sessions for the purpose of developing recommendations on the role of systemic therapy and its optimal sequence in patients with resectable metastatic colorectal cancer.


Assuntos
Neoplasias Gastrointestinais , Neoplasias Hepáticas , Neoplasias Retais , Alberta , Neoplasias Gastrointestinais/terapia , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Retais/terapia
7.
Curr Oncol ; 29(2): 924-927, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35200577

RESUMO

An educational session related to the Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held virtually on 14 October 2020. The WCGCCC is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba), who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists, radiologists, and allied health care professionals participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of total neoadjuvant therapy in rectal cancer.


Assuntos
Neoplasias Gastrointestinais , Neoplasias Retais , Alberta , Consenso , Neoplasias Gastrointestinais/terapia , Humanos , Terapia Neoadjuvante , Neoplasias Retais/terapia
8.
Curr Oncol ; 28(6): 4317-4327, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34898545

RESUMO

The Western Canadian Gastrointestinal Cancer Consensus Conference (WC-5) convened virtually on 10 February 2021. The WC-5 is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of hepatocellular cancer (HCC). Recommendations have been made for the transition from local to systemic therapy and the optimal sequencing of systemic regimens in the management of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Gastrointestinais , Neoplasias Hepáticas , Alberta , Carcinoma Hepatocelular/terapia , Consenso , Neoplasias Gastrointestinais/terapia , Humanos , Neoplasias Hepáticas/terapia
9.
Curr Oncol ; 28(5): 3629-3648, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34590606

RESUMO

The 21st annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Calgary, Alberta, 20-21 September 2019. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists, pathologists, radiologists, and allied health care professionals such as dietitians and nurses participated in presentation and discussion sessions to develop the recommendations presented here. This consensus statement addresses current issues in the management of hepato-pancreato-biliary (HPB) cancers.


Assuntos
Neoplasias Gastrointestinais , Alberta , Consenso , Neoplasias Gastrointestinais/terapia , Humanos , Manitoba , Saskatchewan
10.
Am J Clin Oncol ; 44(9): 487-494, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34269694

RESUMO

AIM: Capecitabine (Cape) is routinely used for the neoadjuvant chemoradiation treatment (NACRT) of locally advanced rectal cancers (LARCs). Previous reports have suggested that the concomitant use of proton pump inhibitors (PPIs) may affect the efficacy of Cape, although the true effect of PPIs when used with Cape as a radiosensitizer for neoadjuvant radiation is unclear. The aim of our study was to evaluate the impact of concurrent PPI use along with fluorouracil (FU) and Cape based NACRT in terms of pathologic and oncological outcomes, in patients with LARC. METHODS: LARC patients treated at our center with NACRT from 2010 to 2016 were identified. Postoperative pathology and follow-up outcomes were examined for any differences with relation to the use of PPIs concurrently with FU and Cape based NACRT and adjuvant chemotherapy regimens. RESULTS: Three hundred four and 204 patients received treatment with FU and Cape based NACRT. No difference in pathologic complete response rate was noted between the 2 arms with the concurrent use of PPIs (25.8% and 25%, respectively, P=0.633); or with and without the use of PPIs in the Cape-NACRT arm specifically (20% and 20.7%, P=0.945). At a median follow-up of 5 years, no statistical difference in local or distant control was noted in the Cape-NACRT patients, with and without concomitant PPI use (P=0.411 and 0.264, respectively).Multivariate analysis showed no association of PPI use and NACRT with Cape, in terms of local control (hazard ratio=0.001, P=0.988) or overall survival (hazard ratio=1.179, confidence interval=0.249-5.579, P=0.835). CONCLUSIONS: Our study revealed that there was no adverse pathologic or oncological outcome with the concurrent use of PPIs along with Cape-NACRT in the treatment of LARC. We report that it may be safe to use PPIs if essential, in this clinical setting, although it would be wise to exercise caution.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Inibidores da Bomba de Prótons/uso terapêutico , Neoplasias Retais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Quimiorradioterapia/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/patologia , Inibidores da Bomba de Prótons/administração & dosagem , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento
11.
Am J Clin Oncol ; 44(4): 158-161, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33625121

RESUMO

OBJECTIVE: The objective of this study was to review real-world patterns of chemotherapy utilization among patients with metastatic gastric/lower esophageal adenocarcinoma with particular focus on the use of ramucirumab plus paclitaxel in previously treated patients. METHODS: This is a retrospective, registry-based study using datasets from Alberta Cancer Registry and other provincial databases in Alberta, Canada. Multivariable logistic regression analysis was used to identify factors associated with palliative chemotherapy use. Among patients who received >1 line of chemotherapy, Kaplan-Meier survival estimates were used to compare outcomes according to ramucirumab plus paclitaxel use. Multivariable Cox regression analysis was then used to identify factors associated with overall survival (OS) in this cohort. RESULTS: A total of 1590 patients were included (including 1070 gastric patients and 520 lower esophageal patients). The following factors were associated with use of palliative chemotherapy: younger age (odds ratio with increasing age: 0.95; 95% confidence interval [CI]: 0.94-0.95), and lower Charlson Comorbidity Index (odds ratio with increasing index: 0.82; 95% CI: 0.74-0.91). Within the subcohort of patients who received >1 line of chemotherapy, use of ramucirumab/paclitaxel was associated with better OS (P=0.033). Multivariable Cox regression analysis suggested that the following factors are associated with better OS: use of ramucirumab/paclitaxel (hazard ratio [HR]: 1.56; 95% CI: 1.07-2.29) and living within urban zones including Calgary or Edmonton zones (vs. Northern zone) (HR for Calgary zone vs. Northern zone: 0.44; 95% CI: 0.23-0.85; HR for Edmonton zone vs. Northern zone: 0.41; 95% CI: 0.22-0.77). CONCLUSIONS: Use of paclitaxel/ramucirumab combination beyond first-line treatment is associated with improved OS among patients with metastatic gastric/lower esophageal adenocarcinoma in this real-world study. Further work is needed to reduce disparity in our health care system between individuals living in rural versus urban areas.


Assuntos
Adenocarcinoma/secundário , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Cuidados Paliativos , Estudos Retrospectivos , Ramucirumab
12.
Int J Colorectal Dis ; 36(3): 493-499, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33068162

RESUMO

OBJECTIVE: To assess the real-world patterns of systemic treatment attrition rates among patients with metastatic colorectal cancer. METHODS: Databases based from the provincial cancer registry and electronic medical records in Alberta were accessed, and cases with a de novo diagnosis of metastatic colorectal cancer with no history of other primary cancers (2004-2017) were reviewed. Rates of chemotherapy administration in first and subsequent lines of treatment were assessed. Multivariable logistic regression analysis for factors associated with non-administration of chemotherapy was evaluated. The impact of administration of all three chemotherapy agents (fluoropyrimidines, oxaliplatin, and irinotecan) across the course of treatment was assessed through multivariable Cox regression analysis with time-dependent covariates. RESULTS: A total of 4179 patients with metastatic colorectal cancer were included in the current study. This includes 1988 patients receiving at least one cycle of chemotherapy and 2191 patients who did not receive any chemotherapy. The following factors were associated with a higher probability of no chemotherapy use: older age (OR 1.064; 95% CI 1.057-1.070), higher Charlson comorbidity index (OR 1.444; 95% CI 1.342-1.554), female sex (OR for male sex versus female sex 0.763; 95% CI 0.660-0.881), rural residence (OR for residence in zone 2 (Calgary) versus zone 5 (North zone) 0.346; 95% CI 0.272-0.440), proximal tumor location (OR 1.255; 95% CI 1.083-1.454), and earlier year at diagnosis (OR (continuous) 0.895; 95% CI 0.879-0.911). Within the cohort of patients who received at least one cycle of chemotherapy, 42.5% received one line of chemotherapy only, and 30.5% received two lines of chemotherapy. The use of all three chemotherapy drugs was associated with better overall survival (HR 3.305; 95% CI 2.755-3.965) and colorectal cancer-specific survival (HR 3.367; 95% CI 2.753-4.117). CONCLUSIONS: A considerable proportion of metastatic colorectal cancer patients who received active chemotherapy in this population-based study received only one line of therapy. This highlights the significance of choosing effective treatments in the first-line treatment as the attrition rate is high. Furthermore, the use of all three chemotherapy agents across the course of treatment was associated with better outcomes.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Masculino , Oxaliplatina
13.
J Oncol Pharm Pract ; 27(7): 1596-1603, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33023385

RESUMO

INTRODUCTION: The study evaluated the effect of chemotherapy dose-capping on disease recurrence, toxicity and survival of rectal cancer patients treated with chemoradiotherapy (CRT). METHODS: 601 consecutive rectal cancer patients treated with concurrent CRT were retrospectively analysed. Dose-capped patients were defined as having a body surface area (BSA) ≥2.0 m2 and who received <95% full weight-based chemotherapy dose. Binary logistic regression was used to study the factors associated with the outcome variables (capped vs. uncapped). Kaplan-Meier estimation evaluated significant predictors of survival. RESULTS: The median follow-up time was 7.54 years. The rate of disease recurrence was significantly higher in dose-capped patients (35%) compared to those without dose-capping (24%, P = 0.016). The adjusted odds ratio for dose-capped patients experiencing recurrence was 1.64 compared to uncapped patients (95% CI, 1.10-2.43). Overall, dose-capped patients were less likely to experience significant toxicity requiring dose reduction and/or treatment break when compared to uncapped patients (15% and 28% respectively, P = 0.008).There was significant differences in PFS between capped and uncapped group (77% vs. 85%; P = 0.017). The 5-year OS in the capped group was 75.0%, and 80% in the uncapped group (P = 0.149). CONCLUSIONS: Rectal cancer patients treated with dose-capped CRT were at increased risk of disease recurrence. Patients dosed by actual BSA did experience excessive toxicity compared to dose-capped group. We recommend that chemotherapy dose-capping based on BSA should not be practiced in rectal cancer patients undergoing CRT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Intervalo Livre de Doença , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Retais/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
14.
Radiother Oncol ; 136: 21-28, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31015125

RESUMO

BACKGROUND AND PURPOSE: We prospectively assessed the contributions of PET to initial staging, early detection of treatment failures, and prognostication in patients with anal squamous cell carcinoma (ASCC). MATERIALS AND METHODS: Consecutive patients with ASCC referred for radical chemoradiotherapy (CRT) consented to undergo FDG-PET imaging pre-treatment and at 3 and 6 months post-treatment. Clinicopathologic data were collected and CT and PET imaging reviewed for contribution to staging and recurrence detection. Maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were assessed for association with progression-free survival (PFS), cause-specific survival (CSS), and overall survival (OS) using the Kaplan-Meier and Cox regression models. RESULTS: Between 2009 and 2016, 73 patients with clinical stages I-IIIB ASCC completed curative-intent CRT. Median follow-up was 48 months. 14 patients died and 18 patients experienced disease progression. 4-year PFS, CSS, and OS were 73%, 87%, and 84%, respectively. A pre-treatment MTV >35 cm3 predicted for worse PFS (p = 0.011) and CSS (p = 0.024) on univariate and multivariate analyses, employing an MTV definition of voxels ≥25% of SUVmax. Higher 6-month post-treatment SUVmax and SUVpeak predicted for worse PFS and OS (p ≤ 0.011). Pre-treatment SUVmax, SUVpeak, and TLG, and 3-month post-treatment SUVmax and SUVpeak did not significantly correlate with survival outcomes. CONCLUSIONS: Our findings support that pre-treatment MTV provides meaningful prognostic information, with suggestion that an MTV delineation threshold of voxels ≥25% of SUVmax is appropriate in the anal region. Post treatment, the combination of clinical examination and PET effectively detected all treatment failures. Higher 6-month post-treatment SUVmax and SUVpeak predicted worse PFS and OS; however, the optimal timing of post-treatment PET imaging remains unclear.


Assuntos
Neoplasias do Ânus/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Adulto , Idoso , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Quimiorradioterapia , Progressão da Doença , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carga Tumoral
15.
Invest New Drugs ; 36(4): 674-682, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29725881

RESUMO

Purpose Chemotherapy remains the primary treatment for metastatic gastric/GEJ cancer but optimal agents and schedule remain controversial. This study examined the safety and efficacy of first-line Irinotecan, capecitabine (Xeloda®), and Oxaliplatin (IXO). Patients and Methods Eligible patients with HER2-unamplified/unknown, metastatic gastric/GEJ adenocarcinoma were treated with 21-day cycle IXO at dose level 1 (DL1: Day 1 O-100 mg/m2 & I-160 mg/m2 IV, Day 2-15 X-1900 mg/m2/day PO divided doses) or modified IXO (mIXO): Day 1 O-85 mg/m2 & I-120 mg/m2 IV, Day 2-15 X-1425 mg/m2/day PO divided doses). This Bryant and Day two-stage designed study had dual primary endpoints of objective response rate (ORR) and toxicity. Secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results Fifty patients were enrolled and received a median of 7 cycles. After accrual of 9 patients at DL1, evaluable RR was 88% however dose limiting toxicity (DLT) rate was 56% thus doses were adjusted to mIXO. Fifteen patients accrued at mIXO had a RR of 60% and DLT rate of 13% allowing continuation to stage 2. Overall, 48 and 49 patients were evaluable for efficacy and safety, respectively, with ORR of 54% and DLTs in 24% of patients (DL1 = 56%; mIXO = 18%). Disease control rate was 85%. The most frequent grade 3/4 adverse events were diarrhea, neutropenia, fatigue, hypokalemia, and nausea. Median PFS and OS were 7.5 and 13.0 months, respectively, with a median follow-up of 9.7 months. Conclusion mIXO demonstrates promising ORR, PFS, OS, and acceptable toxicity compared to standard triplet regimens. IXO should be evaluated in phase III trials.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Capecitabina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Irinotecano/administração & dosagem , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Adulto Jovem
16.
Clin Colorectal Cancer ; 17(2): 156-163, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29486916

RESUMO

BACKGROUND: Capecitabine and oxaliplatin (CAPOX) and folinic acid, fluorouracil, and oxaliplatin (FOLFOX) are both used in the adjuvant treatment of colon cancer, and while their efficacy is assumed to be similar, they have not been directly compared. We reviewed the toxicity profiles, relative dose intensity (RDI), and survival associated with these regimens across a multi-institutional cohort. PATIENTS AND METHODS: We identified 394 consecutively treated patients with stage III colon cancer who received an oxaliplatin-containing regimen. RDI was defined as the total dose received divided by the intended total dose if all cycles were received. RESULTS: FOLFOX was associated with increased mucositis (6.2% vs. 0.7%, P = .0069) and neutropenia (25.9% vs. 8.6%, P < .0001), while CAPOX was associated with increased dose-limiting toxicities (DLTs) (90.7% vs. 80.2%, P = .0055), diarrhea (31.8% vs. 9.0%, P < .0001), and hand-foot syndrome (19.9% vs. 2.1%, P < .0001). Higher median RDI of fluoropyrimidine (93.7% vs. 80.0%, P < .0001) and oxaliplatin (87.2% vs. 76.3%, P < .0001) was noted for patients receiving FOLFOX. Reducing the duration from 6 to 3 months would have prevented 28.7% of FOLFOX and 20.5% of CAPOX patients from ever experiencing a DLT (P = .0008). Overall survival did not differ by regimen (hazard ratio = 0.73; 95% confidence interval 0.45-1.22; P = .24). However, CAPOX was associated with improved disease-free survival (3-year disease-free survival 83.8% vs. 73.4%, P = .022), which remained significant in high-risk (T4 or N2) (P = .039) but not low-risk patients (P = .19). CONCLUSION: CAPOX may be associated with improved disease-free survival despite greater toxicities and lower RDI. Reducing adjuvant chemotherapy duration to 3 months would prevent 26% of patients from ever experiencing a DLT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Neoplasias do Colo/tratamento farmacológico , Idoso , Capecitabina/uso terapêutico , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/uso terapêutico , Estudos Retrospectivos
17.
JAMA Oncol ; 3(6): 767-773, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-27737436

RESUMO

IMPORTANCE: Capecitabine is an oral cytotoxic chemotherapeutic commonly used across cancer subtypes. As with other oral medications though, it may suffer from drug interactions that could impair its absorption. OBJECTIVE: To determine if gastric acid suppressants such as proton pump inhibitors (PPIs) may impair capecitabine efficacy. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of TRIO-013, a phase III randomized trial, compares capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer (GEC); patients were randomized 1:1 between CapeOx with or without lapatinib. Proton pump inhibitor use was identified by medication records. Progression-free survival (PFS) and overall survival (OS) were compared between patients treated with PPIs vs patients who were not. Specific subgroups were accounted for, such as younger age (<60 years), Asian ethnicity, female sex, and disease stage (metastatic/advanced) in multivariate Cox proportional hazards modeling. The TRIO-013 trial accrued and randomized patients between June 2008 and January 2012; this analysis took place in January 2014. INTERVENTIONS: Patients were divided based on PPI exposure. MAIN OUTCOMES AND MEASURES: Primary study outcome was PFS and OS between patients treated with PPIs vs patients who were not. Secondary outcomes included disease response rates and toxicities. RESULTS: Of the 545 patients with GEC (median age, 60 years; 406 men [74%]) included in the study, 229 received PPIs (42.0%) and were evenly distributed between arms. In the placebo arm, PPI-treated patients had poorer median PFS, 4.2 vs 5.7 months (hazard ratio [HR], 1.55; 95% CI, 1.29-1.81, P < .001); OS, 9.2 vs 11.3 months (HR, 1.34; 95% CI, 1.06-1.62; P = .04); and disease control rate (83% vs 72%; P = .02) vs patients not treated with PPIs. In multivariate analysis considering age, race, disease stage, and sex, PPI-treated patients had poorer PFS (HR, 1.68; 95% CI, 1.42-1.94; P < .001) and OS (HR, 1.41; 95% CI, 1.11-1.71; P = .001). In patients treated with CapeOx and lapatinib, PPIs had less effect on PFS (HR, 1.08; P = .54) and OS (HR, 1.26; P = .10); however, multivariate analysis in this group demonstrated a significant difference in OS (HR, 1.38; 95% CI, 1.06-1.66; P = .03). CONCLUSIONS AND RELEVANCE: Proton pump inhibitors negatively effected capecitabine efficacy by possibly raising gastric pH levels, leading to altered dissolution and absorption. These results are consistent with previous erlotinib and sunitinib studies. Whether PPIs affected lapatinib is unclear given concurrent capecitabine. Given capecitabine's prevalence in treatment breast cancer and colon cancer, further studies are under way. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00680901.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Inibidores da Bomba de Prótons/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Capecitabina/administração & dosagem , Interações Medicamentosas , Feminino , Humanos , Lapatinib , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Quinazolinas/administração & dosagem , Resultado do Tratamento
18.
Radiother Oncol ; 120(2): 228-33, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27406441

RESUMO

BACKGROUND AND PURPOSE: Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced anal canal carcinoma, although treatment-related side effects can affect patient quality of life (QOL). The purpose was to prospectively evaluate the effects of Tomotherapy (HT) based CCRT on patient reported QOL in locally advanced anal cancer. PATIENTS AND METHODS: Fifty-four patients treated with HT and concurrent 5-fluorouracil/mitomycin-C underwent QOL evaluation at baseline, after treatment, and during follow-up with EORTC core (QLQ-C30) and colorectal (QLQ-CR29) questionnaires. The QOL scores at baseline and post-treatment were compared. RESULTS: All C30 functional symptoms, except emotional and cognitive functioning, were impaired end-of-treatment and recovered by 3months follow-up. The majority of symptom scores were worse end-of-treatment but recovered by 3months except for fecal incontinence (FI), diarrhea, urinary incontinence (UI), and dyspareunia which persisted. FI returned to baseline at 12months while diarrhea, UI, and dyspareunia persisted. CONCLUSIONS: Most impaired functions and symptoms following HT based CCRT were temporary and improved by 3months post-therapy. Late complications affecting QOL were FI, sexual function, UI, and diarrhea. Our observations support routine use of IMRT and emphasize the significance of precise evaluation of sexual, urinary, and anorectal functions before starting CCRT and routine incorporation of QOL evaluations.


Assuntos
Neoplasias do Ânus/reabilitação , Carcinoma de Células Escamosas/reabilitação , Quimiorradioterapia/efeitos adversos , Qualidade de Vida , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Incontinência Fecal/etiologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Psicometria , Radioterapia de Intensidade Modulada/métodos , Inquéritos e Questionários , Incontinência Urinária/etiologia
19.
Clin Colorectal Cancer ; 15(3): 257-63, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26803708

RESUMO

BACKGROUND: Capecitabine is used to treat colorectal (CRC) cancer. TRIO-013, a study examining capecitabine/oxaliplatin ± lapatinib in metastatic gastro-esophageal cancer did not show increases in overall survival (OS) with lapatinib. An analysis showed concurrent proton pump inhibitor (PPI) usage negatively impacted recurrence-free survival (RFS). We retrospectively studied PPI effects on capecitabine efficacy in early stage CRC and how capecitabine adjustments impacted RFS. METHODS: Early stage CRC patients taking monotherapy capecitabine treated from 2008 to 2012 were reviewed for demographics, medications, toxicities, and patient outcomes. RESULTS: Of 298 identified patients, 25.8% (n = 77) received concurrent PPIs. Five-year RFS was 74% versus 83% (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.07-3.35; P = .03) in PPI versus non-PPI patients respectively. OS was 81% versus 78%, respectively (HR, 1.13; 95% CI, 0.60-2.14; P = .7). After accounting for gender, stage, age, and performance status, PPI patients tended toward decreased RFS (HR, 1.65; 95% CI, 0.93-2.94; P = .09). Capecitabine dose modifications affected outcomes. Five-year RFS was 84% in the control group, 100% in the treatment-delay group (P = .99), 67% in the dose reduction group (HR, 2.46; 95% CI, 1.23-4.93; P = .01), and 64% in the discontinuation group (HR, 2.27; 95% CI, 0.93-5.53; P = .07). Five-year OS was significantly less in the discontinuation group than control group (59% vs. 82%; HR, 3.27; 95% CI, 1.44-7.45; P = .005). CONCLUSIONS: PPIs appear to impact RFS; this may be due to PPIs preventing capecitabine tablet dissolution and absorption. Patients with dose reductions or who stopped treatment had worse outcomes than patients who continued with treatment at starting doses.


Assuntos
Antineoplásicos/uso terapêutico , Capecitabina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Recidiva Local de Neoplasia , Inibidores da Bomba de Prótons/efeitos adversos , Adulto , Idoso , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos
20.
J Oncol Pharm Pract ; 22(3): 454-60, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26002954

RESUMO

BACKGROUND: Capecitabine is a highly water soluble prodrug of 5-fluorouracil that is dosed by patient body surface area. Body surface area dosing makes no allowances for differences in body composition. There is mounting evidence that lean body mass is a better predictor of toxicity than body surface area for drugs which distribute into the lean compartment. Because women, on average, have lower lean body mass than men, we expect that women would experience a higher incidence of toxicity than men when body surface area dosing is used. OBJECTIVE: To determine whether female colorectal cancer patients experienced a higher incidence of dose-limiting toxicity than men when treated with adjuvant capecitabine. METHODS: We conducted a retrospective chart review of colorectal cancer patients treated with adjuvant capecitabine at our institute between 2008 and 2012. Patients receiving capecitabine were identified from the pharmacy dispensing database and then screened for inclusion. Dosing and toxicity information were gathered and dose-limiting toxicity incidence (defined as a composite endpoint of dose delay, dose reduction, or discontinuation of therapy) was compared between males and females using the chi-square test. Binary logistic regression analysis was then performed to account for differences between male and female populations. RESULTS: A total of 299 patients (163 males, 136 females) met inclusion criteria. Females had a significantly higher dose-limiting toxicity incidence than males (67.7 vs. 52.2%, p = 0.007). Relationships between gender and dose-limiting toxicity incidence remained significant after logistic regression analysis (OR: 2.04; 95% CI: 1.23-3.36). CONCLUSION: Female colorectal cancer patients experience a higher dose-limiting toxicity incidence than male patients when given adjuvant capecitabine dosed according to body surface area.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Caracteres Sexuais , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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