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1.
Cochrane Database Syst Rev ; 5: CD011220, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34037241

RESUMO

BACKGROUND: Retrospective analyses suggest that capecitabine may carry superior activity in hormone receptor-positive relative to hormone receptor-negative metastatic breast cancer. This review examined the veracity of that finding and explored whether this differential activity extends to early breast cancer. OBJECTIVES: To assess effects of chemotherapy regimens containing capecitabine compared with regimens not containing capecitabine for women with hormone receptor-positive versus hormone receptor-negative breast cancer across the three major treatment scenarios: neoadjuvant, adjuvant, metastatic. SEARCH METHODS: On 4 June 2019, we searched the Cochrane Breast Cancer Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 5) in the Cochrane Library; MEDLINE; Embase; the World Health Organization International Clinical Trials Registry Platform; and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials looking at chemotherapy regimens containing capecitabine alone or in combination with other agents versus a control or similar regimen without capecitabine for treatment of breast cancer at any stage. The primary outcome measure for metastatic and adjuvant trials was overall survival (OS), and for neoadjuvant studies pathological complete response (pCR). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias and certainty of evidence using the GRADE approach. Hazard ratios (HRs) were derived for time-to-event outcomes, and odds ratios (ORs) for dichotomous outcomes, and meta-analysis was performed using a fixed-effect model. MAIN RESULTS: We included 26 studies with outcome data by hormone receptor: 12 metastatic studies (n = 4325), 6 neoadjuvant trials (n = 3152), and 8 adjuvant studies (n = 13,457). Capecitabine treatment was added in several different ways across studies. These could be classified as capecitabine alone compared to another treatment, capecitabine substituted for part of the control chemotherapy, and capecitabine added to control chemotherapy. In the metastatic setting, the effect of capecitabine was heterogenous between hormone receptor-positive and -negative tumours. For OS, no difference between capecitabine-containing and non-capecitabine-containing regimens was observed for all participants taken together (HR 1.01, 95% confidence interval (CI) 0.98 to 1.05; 12 studies, 4325 participants; high-certainty evidence), for those with hormone receptor-positive disease (HR 0.93, 95% CI 0.84 to 1.04; 7 studies, 1834 participants; high-certainty evidence), and for those with hormone receptor-negative disease (HR 1.00, 95% CI 0.88 to 1.13; 8 studies, 1577 participants; high-certainty evidence). For progression-free survival (PFS), a small improvement was seen for all people (HR 0.89, 95% CI 0.82 to 0.96; 12 studies, 4325 participants; moderate-certainty evidence). This was largely accounted for by a moderate improvement in PFS for inclusion of capecitabine in hormone receptor-positive cancers (HR 0.82, 95% CI 0.73 to 0.91; 7 studies, 1594 participants; moderate-certainty evidence) compared to no difference in PFS for hormone receptor-negative cancers (HR 0.96, 95% CI 0.83 to 1.10; 7 studies, 1122 participants; moderate-certainty evidence). Quality of life was assessed in five studies; in general there did not seem to be differences in global health scores between the two treatment groups at around two years' follow-up. Neoadjuvant studies were highly variable in design, having been undertaken to test various experimental regimens using pathological complete response (pCR) as a surrogate for disease-free survival (DFS) and OS. Across all patients, capecitabine-containing regimens resulted in little difference in pCR in comparison to non-capecitabine-containing regimens (odds ratio (OR) 1.12, 95% CI 0.94 to 1.33; 6 studies, 3152 participants; high-certainty evidence). By subtype, no difference in pCR was observed for either hormone receptor-positive (OR 1.22, 95% CI 0.76 to 1.95; 4 studies, 964 participants; moderate-certainty evidence) or hormone receptor-negative tumours (OR 1.28, 95% CI 0.61 to 2.66; 4 studies, 646 participants; moderate-certainty evidence). Four studies with 2460 people reported longer-term outcomes: these investigators detected no difference in either DFS (HR 1.02, 95% CI 0.86 to 1.21; high-certainty evidence) or OS (HR 0.97, 95% CI 0.77 to 1.23; high-certainty evidence). In the adjuvant setting, a modest improvement in OS was observed across all participants (HR 0.89, 95% CI 0.81 to 0.98; 8 studies, 13,547 participants; moderate-certainty evidence), and no difference in OS was seen in hormone receptor-positive cancers (HR 0.86, 95% CI 0.68 to 1.09; 3 studies, 3683 participants), whereas OS improved in hormone receptor-negative cancers (HR 0.72, 95% CI 0.59 to 0.89; 5 studies, 3432 participants). No difference in DFS or relapse-free survival (RFS) was observed across all participants (HR 0.93, 95% CI 0.86 to 1.01; 8 studies, 13,457 participants; moderate-certainty evidence). As was observed for OS, no difference in DFS/RFS was seen in hormone receptor-positive cancers (HR 1.03, 95% CI 0.91 to 1.17; 5 studies, 5604 participants; moderate-certainty evidence), and improvements in DFS/RFS with inclusion of capecitabine were observed for hormone receptor-negative cancers (HR 0.74, 95% CI 0.64 to 0.86; 7 studies, 3307 participants; moderate-certainty evidence). Adverse effects were reported across all three scenarios. When grade 3 or 4 febrile neutropenia was considered, no difference was seen for capecitabine compared to non-capecitabine regimens in neoadjuvant studies (OR 1.31, 95% CI 0.97 to 1.77; 4 studies, 2890 participants; moderate-certainty evidence), and a marked reduction was seen for capecitabine in adjuvant studies (OR 0.55, 95% CI 0.47 to 0.64; 5 studies, 8086 participants; moderate-certainty evidence). There was an increase in diarrhoea and hand-foot syndrome in neoadjuvant (diarrhoea: OR 1.95, 95% CI 1.32 to 2.89; 3 studies, 2686 participants; hand-foot syndrome: OR 6.77, 95% CI 4.89 to 9.38; 5 studies, 3021 participants; both moderate-certainty evidence) and adjuvant trials (diarrhoea: OR 2.46, 95% CI 2.01 to 3.01; hand-foot syndrome: OR 13.60, 95% CI 10.65 to 17.37; 8 studies, 11,207 participants; moderate-certainty evidence for both outcomes). AUTHORS' CONCLUSIONS: In summary, a moderate PFS benefit by including capecitabine was seen only in hormone receptor-positive cancers in metastatic studies. No benefit of capecitabine for pCR was noted overall or in hormone receptor subgroups when included in neoadjuvant therapy. In contrast, the addition of capecitabine in the adjuvant setting led to improved outcomes for OS and DFS in hormone receptor-negative cancer. Future studies should stratify by hormone receptor and triple-negative breast cancer (TNBC) status to clarify the differential effects of capecitabine in these subgroups across all treatment scenarios, to optimally guide capecitabine inclusion.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Capecitabina/uso terapêutico , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Viés , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Terapia Neoadjuvante , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
2.
Ann Palliat Med ; 10(3): 3009-3017, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33849091

RESUMO

BACKGROUND: This study sought to test the effectiveness of EVOSKIN®Palm and sole moisturizing cream (PSMC) in preventing and treating hand-foot syndrome (HFS) during capecitabine chemotherapy. METHODS: Stage II/III colorectal cancer patients receiving capecitabine adjuvant chemotherapy were randomly allocated to receive either EVOSKINPSMC or physiological saline treatments for their hands and feet. Treatment was initiated along with adjuvant chemotherapy and continued till the end of chemotherapy. Participants' skin responses were evaluated every 3 weeks. RESULTS: During the study, 51 participants in the EVOSKIN PSMC group and 54 participants in the physiological saline group completed at least three cycles of capecitabine chemotherapy. The total incidence of HFS in the EVOSKIN PSMC group was lower than that in the physiological saline group (56.8% vs. 75.9%, P=0.006), as was the incidence of Grade 3/4 HFS (6.0% vs. 18.5%, P=0.011). The incidence of HFS became significant after 6weeks of chemotherapy. Further, the incidence of severe HFS was significant from as early as 3weeks after the commencement of chemotherapy despite the use of EVOSKIN PSMC to manage the condition. Notably, the incidence of Grade 1/2 HFS was not statistically significant between the two groups (26/51 vs. 32/54, 52.0% vs. 59.2%, P=0.194). CONCLUSIONS: The incidence of severe HFS among individuals using oral capecitabine can be reduced by the prophylactic treatment of EVOSKIN PSMC, this treatment is reasonable and acceptable for patients with capecitabine chemotherapy.


Assuntos
Neoplasias Colorretais , Síndrome Mão-Pé , Antimetabólitos Antineoplásicos/uso terapêutico , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Síndrome Mão-Pé/tratamento farmacológico , Síndrome Mão-Pé/etiologia , Humanos
3.
In Vivo ; 35(3): 1881-1884, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33910876

RESUMO

BACKGROUND/AIM: To describe the clinical progress and management of ocular side effects in a 35-year-old patient with metastatic breast cancer who underwent oral chemotherapy with capecitabine and lapatinib. MATERIALS AND METHODS: Slit lamp evaluation revealed bilateral perikeratic hyperemia, perilimbal conjunctival edema associated with corneal marginal infiltrates and epithelial and anterior stromal defects in both eyes. Slit lamp examination, in vivo confocal microscopy and anterior-segment optical coherence tomography were highly suggestive for limbal stem cell deficiency. The decision to administer autologous blood- derived serum eye drops was made. RESULTS: Following administration of autologous blood-derived serum eye drops, corneal marginal infiltrates, epithelial and stromal defects significantly regressed in both eyes after only 10 days. Chemotherapy was resumed and serum eye drops were prescribed simultaneously. CONCLUSION: Autologous blood-derived serum eye drops may be an adequate therapeutic choice for bilateral corneal lesions detected as ocular side effects of capecitabine.


Assuntos
Córnea , Doenças da Córnea , Adulto , Capecitabina/efeitos adversos , Doenças da Córnea/induzido quimicamente , Doenças da Córnea/diagnóstico , Humanos , Soluções Oftálmicas , Soro
4.
Crit Rev Oncol Hematol ; 162: 103346, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33930532

RESUMO

Cancer patients experienced an increased risk of cardiotoxicity during fluoropyrimidine-based chemotherapy (5-fluorouracil or capecitabine). We searched PubMed, PsycINFO, IPA, CINAHL, Web of Science, and ClinicalTrials.gov for studies published between January 1, 1990 and December 31, 2019, in English, examining risk factors for cardiotoxicity induced by fluoropyrimidine. Included study-level data were converted to risk ratios (RRs) and pooled RRs were calculated for meta-analyses using a random-effects method. Among 690 publications identified for abstract and title screening, 22 unique studies were included in the review, and 20 had sufficient data for meta-analyses. Results indicated that patients undergoing capecitabine-based combination therapy had a higher risk than those with monotherapy (pooled RR = 1.61). Patients with pre-existing cardiac disease (pooled RR = 3.26), hypertension (pooled RR = 1.52) or smoking (pooled RR = 2.22) also had higher risks than their counterparts. Developing risk assessment tools to mitigate the risk could be a viable strategy to improve outcomes for cancer patients undergoing fluoropyrimidine-based treatments.


Assuntos
Cardiotoxicidade , Neoplasias , Capecitabina/efeitos adversos , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Fluoruracila/efeitos adversos , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Fatores de Risco
6.
BMJ Case Rep ; 14(3)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762290

RESUMO

An elderly woman with metastatic breast cancer was admitted with hyperglycaemic hyperosmolar state (HHS) and an elevated haemoglobin A1C. For 1 week, she had experienced confusion, nausea and frequent urination. Preceding this, she had completed seven cycles of capecitabine chemotherapy for her breast cancer. She did not have a history of diabetes prior to chemotherapy. Given the temporal dysglycaemia following the patient's chemotherapy regimen, capecitabine was thought to be a probable offending agent. The patient was acutely treated for HHS, and was discharged on a basal-bolus insulin regimen. Her capecitabine was held pending review with her oncology team. The patient was ultimately titrated down to basal insulin only by her family doctor. Given the common use of capecitabine, it is important to recognise the risk of hyperglycaemic and hyperglycaemic emergencies as potential adverse effects. This highlights the need to monitor blood glucose throughout treatment to prevent hyperglycaemic emergencies.


Assuntos
Neoplasias da Mama , Diabetes Mellitus , Hiperglicemia , Coma Hiperglicêmico Hiperosmolar não Cetótico , Idoso , Glicemia , Neoplasias da Mama/tratamento farmacológico , Capecitabina/efeitos adversos , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Coma Hiperglicêmico Hiperosmolar não Cetótico/induzido quimicamente , Coma Hiperglicêmico Hiperosmolar não Cetótico/diagnóstico
7.
BMC Cancer ; 21(1): 179, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607964

RESUMO

BACKGROUND: The management of unresectable locally advanced colon cancer (LACC) remains controversial, as resection is not feasible. The goal of this study was to evaluate the treatment outcomes and toxicity of neoadjuvant chemoradiotherapy (NACRT) followed with surgery and adjuvant chemotherapy in patients with unresectable radically LACC. METHODS: We included patients who were diagnosed at our institution, 2010-2018. The neoadjuvant regimen consisted of radiotherapy and capecitabine/ 5-fluorouracil-based chemotherapy. RESULTS: One hundred patients were identified. The median follow-up time was 32 months. The R0 resection rate, adjusted nonmultivisceral resection rate and bladder preservation rate were 83.0, 43.0 and 83.3%, respectively. The pCR and clinical-downstaging rates were 18, and 81.0%%, respectively. The 3-year PFS and OS rates for all patients were 68.6 and 82.1%, respectively. Seventeen patients developed grade 3-4 myelosuppression, which was the most common adverse event observed after NACRT. Tumor perforation occurred in 3 patients during NACRT. The incidence of grade 3-4 surgery-related complications was 7.0%. Postoperative anastomotic leakage was observed in 3 patients. CONCLUSIONS: NACRT followed by surgery was feasible and safe for selected patients with LACC, and can be used as a conversion treatment to achieve satisfactory downstaging, long-term survival and quality of life, with acceptable toxicities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Qualidade de Vida , Taxa de Sobrevida , Resultado do Tratamento
8.
Medicine (Baltimore) ; 99(51): e23719, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371122

RESUMO

ABSTRACT: Maintenance treatment after first-line chemotherapy for patients with metastatic colorectal cancer (mCRC) is a priority strategy. However, which medicine is chosen is controversial. This study aimed to determine the efficacy and safety of maintenance treatment with metronomic capecitabine vs observation.In this randomized controlled trial, patients who completed 18 weeks of induction chemotherapy with XELOX and achieved disease control were randomly assigned centrally (1:1) to receive maintenance therapy with metronomic chemotherapy or observation until disease progression. The primary endpoint was progression-free survival from randomization; secondary endpoints included overall survival and safety. Analyses were performed by intention to treat.Between January 1st, 2017 and December 31th 2018, 48 patients were enrolled and randomly assigned to receive maintenance treatment with metronomic capecitabine (n = 25) or only observation (n = 23). The median progression-free survival in the metronomic capecitabine group was 5.66 (95% confidence interval [CI] 5.25-6.07) months vs 3.98 (95%CI 3.71-4.24) months in the observation group (hazard ratio 0.11, 95% [CI] 0.04-0.26, P = .000). There was no statistically significant difference in median overall survival: 23.82 (95% CI 22.38-25.25) months in the metronomic capecitabine group vs 21.81 (95% CI 20.23-23.38) months in the observation group (hazard ratio 0.49, 95% CI 0.21-1.11, P = .087). Subgroup analyses were generally consistent with the primary finding. Similar safety profiles were observed in both arms. The most frequent adverse events in metronomic capecitabine group included neutropenia, diarrhea, hand-foot skin reaction, and mucositis.Maintenance therapy with metronomic capecitabine can be considered an alternative option following first-line chemotherapy of XELOX in patients with metastatic colorectal cancer with controlled toxicities.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Oxaloacetatos/uso terapêutico , Administração Metronômica , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Neoplasias Colorretais/patologia , Feminino , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Oxaloacetatos/administração & dosagem , Oxaloacetatos/efeitos adversos , Intervalo Livre de Progressão
9.
Anticancer Res ; 40(7): 4011-4015, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620645

RESUMO

BACKGROUND/AIM: The aim of this monocentric study was to evaluate the efficacy and tolerability of a polychemotherapy regimen based on gemcitabine, docetaxel, capecitabine, cisplatin (PDGX) as second-line for advanced pancreatic cancer after FOLFIRINOX. PATIENTS AND METHODS: Patients received FOLFIRINOX as first-line regimen were retrospectively identified between January 2016 and January 2019. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were treated in our center by PDGX. RESULTS: During this period, 18 patients received PDGX regimen as second-line therapy. Main grade 3 toxicities were hematologic, which required dose adaptation in 14/18 patients. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2,91 and 5,3 months, respectively. Total OS from the initiation of first-line was and 11,9 months. CONCLUSION: Second-line PDGX regimen after FOLFIRINOX failure is feasible, with notable toxicity profile and is associated with poor clinical outcomes.


Assuntos
Adenocarcinoma/tratamento farmacológico , Capecitabina/uso terapêutico , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/efeitos adversos , Cisplatino/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Docetaxel/efeitos adversos , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Resultado do Tratamento
10.
Indian J Gastroenterol ; 39(2): 204-210, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32406009

RESUMO

BACKGROUND: Eppikajututo (TJ-28, a Kampo medicine) is effective against rheumatoid arthritis and eczema. We conducted a randomized comparative trial to assess the efficacy of TJ-28 for preventing hand-foot syndrome (HFS) as a complication of adjuvant chemotherapy using capecitabine. METHODS: The present study was a multi-institutional randomized-controlled trial (UMIN000005899). Colorectal cancer patients scheduled to receive capecitabine chemotherapy as adjuvant therapy were randomly assigned to receive TJ-28 (7500 mg/day) or oral pyridoxine (60 mg/day). Patients were monitored for the development of grade ≥ 2 HFS according to the National Cancer Institute Common Toxicity Criteria until chemotherapy completion. RESULTS: Twenty-two patients were enrolled in this study. The relative dose intensity of capecitabine was 76.2% in the TJ-28 group and 68.2% in the pyridoxine group. Grade ≥ 2 HFS developed in 6 (50.0%) of 12 TJ-28 patients and in 4 (40.0%) of 10 pyridoxine patients. Chemotherapy treatment failure was observed in seven patients, mainly due to HFS, liver dysfunction, diarrhea, and neutropenia. Chemotherapy treatment failure due to HFS occurred in none of the TJ-28 group and 2 patients (20.0%) in the pyridoxine group (p = 0.114). CONCLUSION: Capecitabine-associated HFS was not markedly prevented by TJ-28 compared with pyridoxine. However, TJ-28 might support the continuation of chemotherapy with capecitabine. Further studies are warranted to clarify the benefits of TJ-28.


Assuntos
Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Colorretais/terapia , Síndrome Mão-Pé/etiologia , Síndrome Mão-Pé/prevenção & controle , Resultados Negativos , Preparações Farmacêuticas/administração & dosagem , Fitoterapia , Extratos Vegetais/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piridoxina/administração & dosagem , Adulto Jovem
11.
Pharm Res ; 37(5): 89, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382808

RESUMO

PURPOSE: Capecitabine is an oral pre-pro-drug of the anti-cancer drug 5-fluorouracil (5-FU). The biological activity of the 5-FU degrading enzyme, dihydropyrimidine dehydrogenase (DPD), and the target enzyme thymidylate synthase (TS), are subject to circadian rhythmicity in healthy volunteers. The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), safety, pharmacokinetics (PK) and pharmacodynamics (PD) of capecitabine therapy adapted to this circadian rhythm (chronomodulated therapy). METHODS: Patients aged ≥18 years with advanced solid tumours potentially benefitting from capecitabine therapy were enrolled. A classical dose escalation 3 + 3 design was applied. Capecitabine was administered daily without interruptions. The daily dose was divided in morning and evening doses that were administered at 9:00 h and 24:00 h, respectively. The ratio of the morning to the evening dose was 3:5 (morning: evening). PK and PD were examined on treatment days 7 and 8. RESULTS: A total of 25 patients were enrolled. The MTD of continuous chronomodulated capecitabine therapy was established at 750/1250 mg/m2/day, and was generally well tolerated. Circadian rhythmicity in the plasma PK of capecitabine, dFCR, dFUR and 5-FU was not demonstrated. TS activity was induced and DPD activity demonstrated circadian rhythmicity during capecitabine treatment. CONCLUSION: The MTD of continuous chronomodulated capecitabine treatment allows for a 20% higher dose intensity compared to the approved regimen (1250 mg/m2 bi-daily on day 1-14 of every 21-day cycle). Chronomodulated treatment with capecitabine is promising and could lead to improved tolerability and efficacy of capecitabine.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Capecitabina/administração & dosagem , Capecitabina/farmacologia , Cronoterapia Farmacológica , Neoplasias/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/sangue , Capecitabina/efeitos adversos , Capecitabina/sangue , Ritmo Circadiano , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Feminino , Fluoruracila/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Timidilato Sintase/metabolismo , Uridina Trifosfato/análogos & derivados , Uridina Trifosfato/sangue
12.
Am J Clin Oncol ; 43(5): 305-310, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32343515

RESUMO

OBJECTIVES: Gastrointestinal neuroendocrine carcinoma (NEC) is a lethal, uncommon, and understudied neoplasm. We present the efficacy and safety of first-line capecitabine (CP), oxaliplatin, irinotecan, and bevacizumab (CAPOXIRI-BEV) combination followed by pazopanib plus CP maintenance therapy in patients with advanced high-grade poorly differentiated gastrointestinal NEC. METHODS: This was a two-stage phase II study conducted at multiple institutions. Patients were consecutively enrolled and had advanced NEC of the colon or small bowel. Patients received irinotecan 125 mg/m, oxaliplatin 80 mg/m on day 1, CP 1000 mg/m twice daily on days 1 to 14, plus bevacizumab 8 mg/kg on day 1 for six 21-day cycles. Maintenance therapy was given to those who responded (complete response/partial response) or had stable disease after 6 cycles with CAPOXIRI-BEV with pazopanib 800 mg daily plus CP 1600 mg/m daily on days 1 to 14 every 3 weeks until disease progression or unacceptable toxicity. Patients who progressed on CAPOXIRI-BEV received standard etoposide-carboplatin. The primary endpoint was overall response rate. RESULTS: Twenty-two patients were enrolled of whom 19 were evaluable. The median age was 60 years. The overall response rate (3 complete response/6 partial response) was 47.4% (95% confidence interval: 29.5-76.1), the overall disease control rate was 78.9% (95% confidence interval: 62.6-99.6), and, at median 30 (11 to 41 mo) months' follow-up, 5 patients (26.3%) were still alive. Median progression-free survival was 13 months, and the 1-year progression-free survival rate was 52.6%. The median overall survival was 29 months. The median overall survival of the 9 patients who responded versus those with stable disease/progressive disease was 30.5 versus 14 months, respectively. The median duration of response was 16 months. Predictable toxicity was observed. CONCLUSIONS: First-line CAPOXIRI-BEV followed by pazopanib plus CP maintenance therapy for advanced NEC demonstrates promising efficacy and predictable toxicity. Further investigation is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Neoplasias Gastrointestinais/tratamento farmacológico , Adulto , Idoso , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Carcinoma Neuroendócrino/mortalidade , Feminino , Neoplasias Gastrointestinais/mortalidade , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Intervalo Livre de Progressão , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos
13.
BMJ Case Rep ; 13(3)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32139448

RESUMO

A 49-year-old male carcinoma rectum patient was treated with neoadjuvant FOLFOX (folinic acid, fluorouracil (5-FU) and oxaliplatin) chemotherapy, chemoradiotherapy with capecitabine, surgery and adjuvant FOLFOX. On follow-up, the patient developed a metabolically active liver lesion mimicking metastasis. Liver biopsy and histopathology showed sinusoidal dilatation with non-caseating granulomas. Follow-up fluorodeoxyglucose positron-emission tomography CT scan demonstrated increase in size of the lesion with metabolic activity suspicious of metastasis. The patient underwent segmental liver resection and histopathology showed non-necrotising granuloma with no evidence of malignancy. It is crucial to consider potential side effects of chemotherapeutic agents and have an unbiased approach when evaluating new liver lesions during post treatment follow-up of colorectal cancer. A multidisciplinary tumour board approach comprising of gastroenterologists, medical oncologists, pathologists, radiologists and surgeons is suggested in the management of such patients. The patient is currently doing well and on regular follow-up.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Granuloma/induzido quimicamente , Neoplasias Retais/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Capecitabina/administração & dosagem , Diagnóstico Diferencial , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos
14.
Cancer Chemother Pharmacol ; 85(4): 785-792, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32193619

RESUMO

PURPOSE: Capecitabine is a widely used 5-fluorouracil oral prodrug. Hand-foot syndrome (HFS), one of the most common adverse events of capecitabine, impacts patients' quality of life seriously. The pathogenesis of HFS remains unclear but was usually considered as a type of inflammation conducted by cyclooxygenase-2 (COX-2). The COX-2/PGES/EP signaling pathway plays an important role in the inflammatory reaction. We hypothesized that the single nucleotide polymorphisms (SNPs) in this pathway may be associated with the risk of HFS induced by capecitabine. PATIENTS AND METHODS: Using DNA from blood samples of 225 patients, we genotyped 19 SNPs in 6 core genes (COX-2, PGES, EP1, EP2, EP3, and EP4). Common Terminology Criteria for Adverse Events version 3.0 was used to grade hand-foot syndrome. We used logistic regression analysis to evaluate the correlations between genotype variants and occurrence of HFS. The cumulative incidence of HFS was assessed by Kaplan-Meier analysis. RESULTS: Among the 225 participants, 58.6% (132/225) patients developed into HFS, including 41.3% (93/225) grade 1 HFS, 10.2% (23/225) grade 2 HFS and 7.1% (16/225) grade 3 HFS. Multivariate logistic regression analysis showed the AG/GG genotype of rs3810255 to be associated with a significantly higher risk of grade 2/3 HFS, while the AG/AA genotype of rs17131450 to be associated with a significantly lower risk of grade 2/3 HFS (OR = 3.646, P = 0.011; and OR = 0.266, P = 0.036; respectively). CONCLUSION: Our study showed that rs3810255 AG/GG genotypes and rs17131450 GG genotypes to be associated with high risk of capecitabine-induced HFS.


Assuntos
Capecitabina/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Ciclo-Oxigenase 2/genética , Síndrome Mão-Pé/epidemiologia , Polimorfismo de Nucleotídeo Único , Prostaglandina-E Sintases/genética , Receptores de Prostaglandina E/genética , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Síndrome Mão-Pé/etiologia , Síndrome Mão-Pé/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transdução de Sinais , Neoplasias Gástricas/patologia , Adulto Jovem
15.
Support Care Cancer ; 28(10): 4781-4788, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31974772

RESUMO

PURPOSE: We aimed to identify potential clinical parameters that can be easily obtained by a pre-treatment clinicopathological evaluation and whole blood test to estimate the development of oxaliplatin-induced peripheral neuropathy (OIPN). METHODS: This study was conducted retrospectively. For the FOLFOX regimen, patients received oxaliplatin, 85 mg/m2, every 2 weeks for 12 courses, and with the XELOX regimen, oxaliplatin was 130 mg/m2, every 3 weeks for 6-8 courses. The incidence and degree of neuropathy (NCI-CTCAE v.3) were recorded. RESULTS: A total of 186 patients were included in the study. There were 108 (58%) patients in the grade 0-1 (G0-G1) neuropathy group (mean age 50.5 ± 11.5; 63% men), and 78 (42%) patients in the grade 2-3 (G2-G3) neuropathy group (mean age 58.0 ± 10.8; 46.2% men). The relationship between G2-G3 OIPN development and age (p < 0.001), gender (p = 0.02), and ECOG performance status (p = 0.007) was statistically significant. In the G2-G3 neuropathy group, serum gamma-glutamyl transferase (GGT) (p < 0.001) and glucose (p = 0.007) levels were higher, whereas vitamin D (p < 0.001), hemoglobin (Hgb) (p < 0.001), serum albumin (p = 0.001), and serum magnesium (p = 0.035) levels were lower compared with the G0-G1 neuropathy group. G2-G3 neuropathy was observed in 88% of patients with mucinous carcinoma pathologic type (p < 0.001). CONCLUSION: This study demonstrated that age, histopathologic type, albumin, GGT, glucose, vitamin D, and Hgb levels were the effective factors in prediction of the development of OIPN. In addition, GGT, vitamin D, and Hgb levels were the most effective factor to predict development of OIPN.


Assuntos
Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Incidência , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina/administração & dosagem , Oxaloacetatos/administração & dosagem , Oxaloacetatos/efeitos adversos , Doenças do Sistema Nervoso Periférico/sangue , Doenças do Sistema Nervoso Periférico/patologia , Estudos Retrospectivos , Vitamina D/sangue
16.
Trials ; 21(1): 89, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941523

RESUMO

BACKGROUND: A substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year. Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement. Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications. However, there remains a need for further treatment options for patients with bone metastases. Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects. METHODS/DESIGN: CARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy. DISCUSSION: The CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer. If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit. TRIAL REGISTRATION: ISRCTN, ISRCTN92755158, Registered on 17 February 2016.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Capecitabina/uso terapêutico , Rádio (Elemento)/uso terapêutico , Administração Oral , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Remodelação Óssea/efeitos dos fármacos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Humanos , Metástase Neoplásica/patologia , Radioisótopos/administração & dosagem , Radioisótopos/efeitos adversos , Radioisótopos/uso terapêutico , Rádio (Elemento)/administração & dosagem , Rádio (Elemento)/efeitos adversos , Segurança , Resultado do Tratamento
17.
N Engl J Med ; 382(7): 597-609, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-31825569

RESUMO

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase. METHODS: We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety. RESULTS: Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group. CONCLUSIONS: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Capecitabina/administração & dosagem , Oxazóis/administração & dosagem , Proteínas Tirosina Quinases/antagonistas & inibidores , Piridinas/administração & dosagem , Quinazolinas/administração & dosagem , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Encefálicas/secundário , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Capecitabina/efeitos adversos , Quimioterapia de Consolidação , Diarreia/induzido quimicamente , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Oxazóis/efeitos adversos , Intervalo Livre de Progressão , Piridinas/efeitos adversos , Quinazolinas/efeitos adversos , Receptor ErbB-2/análise , Trastuzumab/efeitos adversos
18.
Support Care Cancer ; 28(8): 3649-3657, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31811480

RESUMO

PURPOSE: Capecitabine-based adjuvant chemotherapy for colorectal cancer patients often causes adverse events (AEs), such as diarrhea, stomatitis, anorexia, and hand-foot syndrome (HFS). Cystine and theanine were reported to attenuate some chemotherapy-associated AEs, and hence are also expected to attenuate capecitabine-induced AEs. Therefore, we aimed to investigate the safety and efficacy of cystine/theanine treatment in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery. METHODS: A total of 100 colorectal cancer patients treated with capecitabine as an adjuvant chemotherapy after surgery were randomly allocated into the cystine/theanine group (n = 52) or the placebo group (n = 48). The primary endpoint was incidence rate of diarrhea of grade 1 or higher in accordance with the Common Terminology Criteria for AEs (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. The secondary endpoints included incidence rates of other AEs (CTCAE v.4.0-JCOG), as well as the incidence rate of HFS according to the HFS grading scale. RESULTS: There were no significant differences in capecitabine-induced AEs between the two groups. However, the incidence rate of diarrhea of grade 1 or higher tended to be lower in the cystine/theanine group than the placebo group (18.4% vs. 28.9%, p = 0.169) as well as the incidence rate of HFS of grade 1 or higher (CTCAE v.4.0-JCOG or HFS grading scale) (67.4% vs. 77.8%, p = 0.185, 67.3% vs. 80.0%, p = 0.124, respectively). CONCLUSION: This trial demonstrated that cystine/theanine treatment of colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery is safe and has the tendency to reduce the incidence rate of diarrhea or HFS. TRIAL REGISTRATION: UMIN000024784.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Cistina/uso terapêutico , Glutamatos/uso terapêutico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anorexia/induzido quimicamente , Anorexia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Neoplasias Colorretais/cirurgia , Cistina/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Feminino , Glutamatos/efeitos adversos , Síndrome Mão-Pé/tratamento farmacológico , Síndrome Mão-Pé/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico
19.
Anticancer Drugs ; 31(1): 73-75, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31567310

RESUMO

Anal canal adenocarcinoma is generally treated like rectal cancer. Surgery is the standard treatment in early stages and neoadjuvant chemoradiation in locally advanced tumors. Local recurrences treatment paradigm often depends on the previous therapies of either surgery or radiotherapy or systemic therapy. We present the case of a patient with tubulovillous adenocarcinoma of the anal canal which relapsed after chemoradiation. The patient refused salvage surgery and was treated with definitive electrochemotherapy under general anesthesia. Tumor electroporation performed with the insertion of three needles in the recurred site was preceded by an intravenous bolus of bleomycin. After the administered treatment, the patient showed a complete clinical response. A year after electrochemotherapy, the patient is free from local disease with excellent preservation of the sphincter function. Electrochemotherapy may be considered as an alternative to surgery in small lesion in the anorectal region when other approaches are excluded.


Assuntos
Adenocarcinoma/tratamento farmacológico , Capecitabina/administração & dosagem , Eletroquimioterapia/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina/efeitos adversos , Humanos , Masculino
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