RESUMO
BACKGROUND: Regorafenib(Rego)is the salvage line standard treatment for metastatic colorectal cancer(mCRC), which often causes severe toxicities, such as hand-foot syndrome. Previously, we reported that in phase â ¡ study, S-1 plus bevacizumab( Bev)(SB)showed favorable anticancer activity and feasibility as a salvage line. The aim of this study was to evaluate 2 treatments for mCRC as salvage line. PATIENTS AND METHODS: In this multicenter phase â ¡ study, the patients were randomly assigned(1:1)to the Rego or SB group. In the Rego group, Rego 160 mg/kg body weight was orally administered every 28 days for 21 days. In the SB group, S-1 was orally administered every 42 days for 28 days, according to body surface area, and Bev 5 mg/kg was administered by intravenous infusion on days 1, 15, and 29. Administration of S-1 every 21 days for 14 days and Bev 7.5 mg/kg on day 1 was also permitted. The primary endpoint was overall survival(OS), and the planned sample size was 86. RESULTS: This study was ended prematurely due to poor accrual. Overall, 8 patients were enrolled from 6 institutions between Oct 2013 and May 2015. Although 4 patients were assigned to each group, one patient in the Rego group was excluded after enrollment. The median OS in the Rego and SB groups was 30.2 months and 6.6 months, respectively(hazard ratio: 0.205, p=0.123). The median progression-free survival in the Rego and SB groups was 3.7 months and 1.6 months, respectively. The disease control rate in the Rego and SB groups was 100% and 75%, respectively. The Grade 3 or 4 adverse events were increased, including AST/ALT(n=1, 25%), hyponatremia(n=1, 25%), hand-foot syndrome(n=1, 25%), hypertension(n=1, 25%), and proteinuria(n=1, 25%)in the Rego group and colitis( n=1, 25%)in the SB group; the treatment was discontinued. CONCLUSION: Despite the fact that data could only be collected from a small number of patients, SB is not recommended as salvage line for mCRC.
Assuntos
Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Humanos , Compostos de Fenilureia/uso terapêutico , PiridinasRESUMO
BACKGROUND: Fluorouracil and leucovorin combined with oxaliplatin or irinotecan plus bevacizumab (Bmab) or cetuximab (Cmab) are now widely accepted treatment options as first-line or second-line chemotherapy for metastatic colorectal cancer (mCRC). Sequential chemotherapy with oral 5-FU backbone for mCRC without using central venous ports is beneficial for both patients and physicians. We designed the SOBIC trial to validate the effectiveness of the first- and second-line oral combination chemotherapy for mCRC. PATIENTS AND METHODS: From May 2010 through March 2013, 52 patients were enrolled from 47 institutions in the Hyogo Colorectal Cancer Surgery Group. First-line chemotherapy was S-1 + oxaliplatin (SOX) plus Bmab, and second-line chemotherapy after first-line failure was irinotecan + S-1 (IRIS) + Cmab, IRIS + Bmab, or IRIS based on the KRAS status. RESULTS: The 50 finally included patients received first-line chemotherapy. Second-line therapy was administered to 20 patients (40%): 12 patients received IRIS + Cmab and 8 patients received IRIS + Bmab. The median follow-up period was 48.6 months (range 35-67 months). The median second progression-free survival was 24.2 months (95% confidence interval [CI] 17.7-35.2). The response rate after first- and second-line chemotherapy was 46.7% and 15%, respectively. The median overall survival was 35.2 months (95% CI: 27.8 to not reached). The main grade 3-4 adverse events were sensory neuropathy (18%) and fatigue (10%). There were no treatment-related deaths. CONCLUSION: Sequential S-1-based combination regimens including oxaliplatin, irinotecan, Bmab, and Cmab were beneficial for patients with mCRC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Bevacizumab/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Ácido Oxônico/uso terapêutico , Intervalo Livre de Progressão , Tegafur/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Older or frail patients are often underrepresented in clinical trials for metastatic colorectal cancer (mCRC). We here assessed the efficacy and safety of 5-fluorouracil (5-FU)-leucovorin plus bevacizumab in such patients. METHODS: The study (OGSG 0802) was designed as a single-arm, open-label, multicenter phase II trial. Eligible patients had mCRC and at least one of the following: an age of ≥ 65 years, an Eastern Cooperative Oncology Group performance status of 1 or 2, a serum albumin level of ≤ 3.5 g/dL, incompatibility with oxaliplatin or irinotecan, and a history of abdominal or pelvic radiotherapy. Patients received 5-FU (600 mg/m2) and l-leucovorin (200 mg/m2) on days 1, 8, and 15 together with bevacizumab (5 mg/kg) on days 1 and 15 every 4 weeks. The primary end point was objective response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty-one patients were enrolled and eligible. Median age was 76 years (range 56-90 years), and 51% of patients had a performance status of 0. The ORR was 36.6% [95% confidence interval (CI) 22.1-53.1%], median PFS was 9.4 months (95% CI 7.4-17.7 months), and median OS was 24.0 months (95% CI 19.9 months-not reached). The most common treatment-related adverse events of grade ≥ 3 were neutropenia (24%), anorexia (10%), leukopenia (7%), and mucositis/stomatitis (7%). There were no treatment-related deaths. CONCLUSION: Weekly 5-FU-leucovorin with biweekly bevacizumab may be a tolerable and effective treatment option for older or frail patients with mCRC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Idoso Fragilizado , Humanos , Irinotecano/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/efeitos adversos , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this multicenter, open-label, randomized phase II trial was to evaluate the efficacy of a dose-dense capecitabine and oxaliplatin (XELOX) regimen in patients with metastatic colorectal cancer (mCRC) for whom reintroduction of oxaliplatin had been planned as a third- or later-line regimen. METHODS: The patients with mCRC who had received prior chemotherapy including oxaliplatin and were scheduled for reintroduction of oxaliplatin were randomized to capecitabine (1,000 mg/m(2)) twice daily on days 1-14 and oxaliplatin (130 mg/m(2)) on day 1 every 21 days (Q3W group) or capecitabine (2,000 mg/m(2)) twice daily on days 1-7 and oxaliplatin (85 mg/m(2)) on day 1 every 14 days (Q2W group). The primary endpoint was the time-to-treatment failure (TTF). Other endpoints included overall survival (OS), progression-free survival (PFS) and other adverse events (AEs). RESULTS: A total of 46 patients were enrolled in the trial-22 patients were randomly assigned to the Q3W group and 23 to the Q2W group. The median TTF was 3.4 months in both groups (hazard ratio [HR] 1.053; p = 0.880). The median PFS and OS were 3.3 and 9.2 months in the Q2W group and 4.3 and 12.1 months in the Q3W group, respectively (HR 1.15; p = 0.153 and 0.672; p = 0.836). The most common grade 3-4 AEs in the Q3W and Q2W groups were fatigue (27.3 vs 21.7), neuropathy (9.1 vs 0 %) and diarrhea (9.1 vs 0 %), respectively. CONCLUSION: There was no significant inter-group difference in any of the efficacy and safety endpoints, including TTF, OS, RFS and AEs. The results of this clinical trial were convincingly negative.
Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Compostos Organoplatínicos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Esquema de Medicação , Fadiga/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Doenças do Sistema Nervoso/induzido quimicamente , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Oxaloacetatos , Retratamento , Taxa de SobrevidaRESUMO
BACKGROUND: Perineal approaches are widely applied for the treatment of rectal prolapse. Recently, less-invasive treatments such as sclerotherapy using aluminum potassium sulfate/tannic acid (ALTA) have been introduced for internal hemorrhoids. Herein, we report the results of ALTA injection for the treatment of rectal prolapse in high-risk patients. METHODS: Between January 2009 and March 2011, we performed ALTA injection sclerosing therapy in 12 female patients with high risk for preoperative complications. Using the perineal approach, 0.5 to 1 mL of ALTA was injected into the submucosa at 30 to 60 different sites. RESULTS: All patients were successfully treated without any operative or postoperative morbidity. Average operation time took 35±7 (mean±SD) minutes, and average volume of ALTA injected was 39±6 mL per patient. Neither complaints of bleeding nor findings of anal stenosis were noted. A slight degree of recurrence of prolapse developed in a patient after 8 months. The patient required an additional injection to be cured. CONCLUSIONS: ALTA injection could be administered for the treatment of rectal prolapse without any pain or complication and would be useful even for patients with risks due to preoperative complications and/or medical history.
Assuntos
Prolapso Retal/terapia , Soluções Esclerosantes/administração & dosagem , Escleroterapia/métodos , Idoso , Idoso de 80 Anos ou mais , Compostos de Alúmen/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Injeções , Recidiva , Estudos Retrospectivos , Taninos/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVE: S-1 and cisplatin combination therapy is a standard regimen for patients with advanced gastric cancer in Japan. The primary objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of a triplet regimen adding paclitaxel to S-1 and cisplatin combination therapy. METHODS: Patients with previously untreated metastatic or recurrent gastric cancer were enrolled. Patients received S-1 (40 mg/m(2) p.o., twice daily, on days 1-21 every 35 days), cisplatin (30 mg/m(2) divided, on days 1 and 15) and paclitaxel (divided on days 1 and 15). The starting dose of paclitaxel was 50 mg/m(2) (level 1); the dose was escalated to 60 (level 2), 70 (level 3) and 80 mg/m(2) (level 4) in a stepwise fashion. Dose-limiting toxicity was determined during the first treatment cycle. RESULTS: Eighteen patients enrolled. During the first cycle, no dose-limiting toxicity was observed at dose levels 1 and 2. At dose level 3, one of the six patients had dose-limiting toxicity (one patient had grade 4 neutropenia) and at dose level 4, one of the six patients had dose-limiting toxicity (one patient had febrile neutropenia, hypoalbuminemia and fatigue of grade 3). The maximum tolerated dose was not reached at level 4; however, grade 3 hyponatremia and hypokalemia in two of the six patients occurred during the second treatment course at level 4. From the point of view of safety in the outpatient setting, the recommended dose of paclitaxel was determined at 70 mg/m(2). The overall response rate was 50%. CONCLUSIONS: The recommended dose of paclitaxel added to S-1 (80 mg/m(2) days 1-21) plus cisplatin (30 mg/m(2) days 1 and 15) was 70 mg/m(2) on days 1 and 15 of a 5-week cycle.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Esquema de Medicação , Combinação de Medicamentos , Fadiga/induzido quimicamente , Feminino , Humanos , Hipoalbuminemia/induzido quimicamente , Hipopotassemia/induzido quimicamente , Hiponatremia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSES: We have devised a modified seton technique that resects the external fistula tract while preserving the anal sphincter muscle. This study assessed the technique when used for the management of complex anal fistulas. METHODS: Between January 2006 and December 2007, 239 patients (208 males and 31 females, median age: 41 years) underwent surgery for complex anal fistulas using the technique. Of the 239 patients, 198 patients had trans-sphincteric fistula and 41 patients had supra-sphincteric fistula. RESULTS: The durations of the surgeries were 17 min (47, 13) [median (range, interquartile range)] for trans-sphincteric fistulas and 38 (44, 16) for supra-sphincteric fistulas. The durations of the surgeries were significantly (P < 0.05) longer for supra-sphincteric fistula than trans-sphincteric fistula. The hospital stays were 4 (13, 2) days and 5 (14, 3) days, respectively, for trans- and supra-sphincteric fistulas. The durations of seton placement until the spontaneous dropping of the seton were 42 (121, 48) and 141 (171, 55) days respectively. The recurrence rate was 0 % in patients with trans-sphincteric fistulas and 4.9 % (2 of 41) in patients with supra-sphincteric fistulas (P < 0.01). Serious incontinence was not observed. CONCLUSIONS: The technique provided favorable results for the treatment of complex anal fistulas and could be safely applied while preserving the sphincter function and conserving fecal continence.
Assuntos
Canal Anal/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Fístula Retal/cirurgia , Técnicas de Sutura , Adulto , Defecação , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Fístula Retal/fisiopatologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: It is unclear whether S-1 plus cisplatin is effective for patients with recurrent gastric cancer after adjuvant S-1 chemotherapy. METHODS: We retrospectively evaluated the efficacy of S-1 plus cisplatin in patients whose gastric cancer recurred after adjuvant S-1 chemotherapy. RESULTS: In the 52 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 8.1 months, and the median recurrence-free interval (RFI) since the last administration of adjuvant S-1 was 6.4 months. Among the 36 patients with measurable lesions, 7 achieved a complete or partial response, and 13 were evaluated as having stable disease, for an overall response rate of 19.4% and a disease control rate of 55.6%. For all patients, the median progression-free survival (PFS) was 4.8 months, and the median overall survival (OS) was 12.2 months. Compared with patients with an RFI of <6 months (n = 25), patients with an RFI of ≥6 months (n = 27) had a significantly higher response rate (5.0 vs. 37.5%, respectively), longer PFS (2.3 vs. 6.2 months, respectively), and longer overall survival (7.3 vs. 16.6 months, respectively). According to a multivariate Cox model including performance status (PS) and reason for discontinuation of adjuvant S-1, an RFI of 6 months was still significantly associated with PFS and OS. CONCLUSIONS: S-1 plus cisplatin is effective for patients with gastric cancer that recurs after adjuvant S-1 chemotherapy, especially for those with an RFI of ≥6 months.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Ácido Oxônico/administração & dosagem , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Resultado do TratamentoRESUMO
UNLABELLED: In colorectal cancer (CRC), 5-fluorouracil (5-FU) has been a basic chemotherapeutic agent. Orotate phosphoribosyltransferase (OPRT) and thymidine phosphorylase (TP) are essential enzymes for activation of 5-FU. Dihydropyrimidine dehydrogenase (DPD) is an enzyme for degradation. The feasibility of individualized chemotherapy was studied using the enzyme expression and drug sensitivity test. METHODS: The study included 160 surgical patients (stage II to IV). OPRT, TP, and DPD expressions, assessed with immunohistochemistry, were evaluated in relation to clinicopathological features and patient survival. We assessed 5-FU sensitivity using the collagen gel droplet. Embedded culture-drug sensitivity test(CDDST). The area under the concentration curve (AUC) and growth inhibition curve (IR) were combined in the AUC-IR curve, according to which the individual AUC(IR50) was calculated. Durations to achieve AUC(IR50) were calculated using AUC(24hr) values in UFT and S-1. RESULTS: TP and DPD expression were positively associated with CRC progression and related with poor prognosis, although OPRT expression was negatively associated with CRC progression and related with better prognosis. Patient survival was best in patients with OPRT (+) DPD (-), and worst in those with OPRT (-) DPD (+). Individual AUC(IR50) ranged from less than 100 mg·hr/mL to more than 10,000 mg·hr/mL. In the chemotherapy with UFT, 55% of patients achieved AUC(IR50) within 6 months, 13% of patients achieved it 6 to 12 months, another 13% of patients in 12 to 24 months, and the other 19% after 24 months of chemotherapy. In the chemotherapy with S-1, 31% of patients achieved AUC(IR50) within 1 course, 15% in 1 to 2 courses, another 23% in 2 to 6 courses and the other 31% of patients achieved AUC(IR50) after 6 courses. CONCLUSIONS: The present results suggest that patients' prognosis may be improved with selection of an anti-cancer drug based on the 5-FU metabolizing enzyme expressions and prognostic factors. CD-DST may predict the duration of chemotherapy.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/enzimologia , Idoso , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Sensibilidade e EspecificidadeRESUMO
UNLABELLED: Injectable combination chemotherapy with 5-fluorouracil (5-FU)/Leucovorin (LV), oxaliplatin (OHP), and irinotecan (CPT-11) has been a standard treatment for advanced colorectal cancer (CRC). An oral fluoropyrimidine, S-1 (tegafur, gimeracil, and oteracil), has been developed recently, and a combination of S-1/CPT-11 demonstrated effects comparable to FOLFIRI for the treatment of advanced CRC. Being without continuous infusion lasting for days, combination chemotherapy with oral fluoropyrimidine may limit inconvenience and improve the quality of life (QOL) of patients. There have been few studies evaluating chemotherapy with oral fluoropyrimidine in terms of patient QOL and convenience. PATIENTS AND METHODS: We assessed the patients' QOL by questionnaire, comparing experiences of those treated with S-1/CPT-11 to those treated with mFOLFOX6 in patients with advanced CRC. The questionnaire, selected from EORTC QLQ, FACT-G, and FACT/GOG-Ntx, consisted of six categories: moving activity, willingness, pain and numbness, gastrointestinal symptoms, daily life, and convenience. The questionnaire had 5 questions in each category and a total of 30 questions. RESULTS: Patients' background and characteristics were similar. No significant difference was observed in response rates and time to progression between the groups. As for adverse effects, there was a case of fatigue (grade 2), five cases of neurotoxicites (grade 1 and 2) in mFOL-FOX6, and a case of diarrhea (grade 3) in S-1/CPT-11. No difference between the two groups was observed in responses to the questionnaire asking about moving activity, willingness, gastrointestinal symptoms, and daily life. As for neurotoxicity and convenience, however, S-1/CPT-11 showed significantly better results than mFOLFOX6. CONCLUSION: The present results suggest that questionnaires are useful for assessing patients' QOL with advanced CRC treated chemotherapy. Combination chemotherapy with oral fluoropyrimidine S-1 could provide similar response rates, limit inconvenience, and improve QOL.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Qualidade de Vida , Tegafur/uso terapêutico , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/uso terapêutico , Combinação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Irinotecano , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/uso terapêutico , Ácido Oxônico/administração & dosagem , Inquéritos e Questionários , Tegafur/administração & dosagemRESUMO
BACKGROUND: We retrospectively compared the results of sclerotherapy with a new sclerosing agent (aluminum potassium sulphate/tannic acid) and hemorrhoidopexy using an improved type of circular stapler with hemorrhoidectomy. METHODS: Between January 2006 and September 2008, we performed hemorrhoidectomy in 416 patients, sclerotherapy in 784 patients and hemorrhoidopexy in 118 patients with prolapsing internal hemorrhoids. RESULTS: The median volume of the agent injected into a hemorrhoid was 7 ml (interquartile range = 4). The operation duration was significantly shorter (p < 0.01) in sclerotherapy, 13 min (interquartile range = 7), than in hemorrhoidectomy, 43 min (interquartile range = 15), and hemorrhoidopexy, 31 min (interquartile range = 16). Postoperative pain, needing pain killer injection, occurred in 59 patients (14%) in hemorrhoidectomy, 14 patients (1.8%) in sclerotherapy and 1 patient (0.8%) in hemorrhoidopexy (p < 0.01). The disappearance rates of prolapse were 100% (416/416 patients) in hemorrhoidectomy, 96% (753/784 patients) in sclerotherapy and 98.3% (116/118 patients) in hemorrhoidopexy. CONCLUSIONS: Hemorrhoidectomy, widely applied for hemorrhoids, needs hospitalization, being accompanied by pain. Sclerotherapy could be performed on outpatient bases without any severe pain or complication. Hemorrhoidopexy is a useful alternative treatment with less pain. Less invasive treatments would be useful when performed paying attention to avoid complications.
Assuntos
Compostos de Alúmen/uso terapêutico , Hemorroidas/terapia , Soluções Esclerosantes/uso terapêutico , Escleroterapia , Grampeamento Cirúrgico , Taninos/uso terapêutico , Assistência Ambulatorial , Feminino , Hemorroidas/cirurgia , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória , Prolapso , Estudos Retrospectivos , Grampeadores Cirúrgicos , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: In colorectal cancer (CRC), 5-fluorouracil (5-FU) has been a basic chemotherapeutic agent. Antitumor effects of 5-FU and its derivatives are likely due to inter-individual difference in the drug sensitivity. METHODOLOGY: We evaluated the 5-FU sensitivity of cancer cells from CRC patients using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) under multiple drug concentration and contact durations. The area under the concentration curve (AUC) and growth inhibition curve (IR) were combined in the AUC-IR curve. Using the AUC-IR curve, the individual AUC(IR50) was calculated. Furthermore, using the AUC values of 5-FU during 24 hours with chemotherapy with UFT and S-1, the durations to achieve the AUC(IR50) were calculated in chemotherapy with UFT or S-1 for individual patient. RESULTS: The value of individual AUC(IR50) ranged widely from less than 100 microg hr/ml to more than 1000 microg hr/ml. Approximately 13% of patients demonstrated a relatively low 5-FU sensitivity. Durations of chemotherapy to achieve the AUC(IR50) differed widely depending on the AUC(IR50) of individual patient. Relapse free survival was significantly better in the patients who have achieved individual AUC(IR50) than those who have not achieved the AUC(IR50). CONCLUSIONS: The present results suggest that the antitumor effects of 5-FU and its derivatives differ widely depending on inter-individual difference of sensitivity, and that individual AUC(IR50) may be useful to predict the optimal duration of chemotherapy.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Fluoruracila/farmacologia , Adulto , Idoso , Área Sob a Curva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
We report here two cases of recurrent gastric cancer after post operative adjuvant chemotherapy, in which S-1 has been effective to control the recurrence and provided long-term survival. Case 1: A 75-year-old male presented with malaise. Endoscopy showed an advanced gastric cancer. He underwent total gastrectomy with lymph adenectomy and received adjuvant chemotherapy with 3 courses of weekly paclitaxel and 6 months of UFT. An abdominal tumor developed with elevation of tumor markers 1 year and 2 months after surgery. After 5 courses of S-1(100mg/day), the tumor resolved and a complete response(CR)was obtained with decline of the markers for 2 years. Case 2: A 62-year-old male presented with abdominal pain. Endoscopy showed an advanced gastric cancer. He underwent distal gastrectomy with lymph adenectomy. Peritonitis carcinomatosa developed with ascites though adjuvant chemotherapy with UFT had been continued for 6 months after paclitaxel. After 10 courses of S-1(100 mg/day), ascites disappeared with decline of the markers. He has been well without any sign of recurrence or elevation of tumor markers for 2 years. Differences in the 5-fluorouracil concentration of UFT and that of S-1 may explain the effectiveness of S-1 for recurrence of gastric cancer after adjuvant chemotherapy with UFT.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Combinação de Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Recidiva , Indução de Remissão , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , Tomografia Computadorizada por Raios X , Uracila/administração & dosagem , Uracila/uso terapêuticoRESUMO
BACKGROUNDS/AIMS: Laparoscopic hepatectomy may provid a less invasive treatment and diagnostic modality. To date, however, few reports have been published on a clinical usefulness of laproscopic hepatectomy using vessel sealer (VS) and soft-coagulation system (SC) for small hepatic tumors suspected of malignancy. METHODOLOGY: Case 1; A 58-year-old man presented with a small hepatic tumor, detected during a medical examination. Image sutdies including ultrasonography, magnetic resonance image and angiography suspected it as hepatocellular carcinoma (HCC), adenoma, angiomyolipoma, or focal nodular hyperplasia (FNH). Laparoscopic hepatectomy was performed after enhanced ultrasonography. Histopathological diagnosis was FNH. Case 2; A 57-year-old man presented with a small hepatic tumor, detected during a medical examination. Image stuides suspected it as HCC or adenoma. Laparoscopic medial segmentectomy was performed. Histopathological diagnosis was HCC. Case 3; A 59-year old man with a history of early colon cancer presented with a small hepatic tumor, detected during a routine check-up. Image studies showed it, and laparoscopic lateral segmentectomy was performed. Histopathological diagnosis was adenocarcinoma. Using VS and SC, laparoscopic hepatectomy was performed safely without any morbidity. Glisson's trunk and the left hepatic vain were transected with endo-linear staplers. DISCUSSIONS: It has been difficult to obtain a biopsy specimen from small lesions and make a denifite diagnosis even with the specimen. There are risks of dissemination and route recurrence. Recurrence rates have been reported to be relatively high after radio frequency ablation. Laparoscopic hepatectomy represents an intermediate option between ablation therapy and conventional hepatectomy. CONCLUSIONS: Laparoscopic hepatectomy using VS and SC may be a less invasive and radical treatment as well as an useful diagnostic modality for small hepatic tumors suspected of malignancy.
Assuntos
Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Hepatectomia/instrumentação , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
We report a case of disease-free survival with low-dose of uracil-tegafur (UFT) after reaction of hepatic and pulmonary metastases from rectal cancer. A 58-year-old male had a medical history of low anterior resection of the rectal cancer. Hepatic and pulmonary metastases developed 3 years and 3 months after the primary operation. Image studies including computed tomography, ultrasonography, and angiography showed multiple metastases in the liver and lung. Two surgeries were performed to resect all of them, followed by adjuvant chemotherapy with low-dose UFT due to relatively low platelet counts. After surgery, the patient has been well without any sign of recurrence or elevation of tumor markers for 2 years and 10 months. This case indicated the usefulness of surgical resection of hepatic and pulmonary metastases, followed by low-dose adjuvant chemotherapy.
Assuntos
Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Pneumonectomia , Neoplasias Retais/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Tegafur/administração & dosagem , Uracila/administração & dosagemRESUMO
BACKGROUND: An oral combined fluoropyrimidine, S-1 (tegafur, gimeracil and oteracil) has recently been used alone or in combination for colorectal cancer (CRC). CASE AND METHODS: A 67-year-old man underwent left hemicolectomy for the descending colon cancer with multiple hepatic metastases. A combined chemotherapy with S-1 and irinotecan (CPT-11) was started after surgery. After three courses of the chemotherapy, no metastasis was observed in contrast computed tomography with decline of tumor markers. The patient was judged to have achieved a complete response (CR). The chemotherapy, continued on an outpatient basis, has maintained the CR for 15 months so far, though adverse reactions such as neutropenia, thrombocytopenia, and hypolacrimia have occurred. CONCLUSION: This case indicates that the combination of S-1 and CPT-11 is feasible on an outpatient basis and has potential as one of the treatment choices for hepatic metastasis from CRC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias do Colo/patologia , Combinação de Medicamentos , Humanos , Irinotecano , Masculino , Ácido Oxônico/administração & dosagem , Tegafur/administração & dosagemRESUMO
We report a case in which combination chemotherapy with oral fluoropyrimidine and weekly paclitaxel was effective for gastric cancer with peritoneal dissemination. A 44-year-old woman suffering from advanced gastric cancer with peritoneal dissemination underwent total gastrectomy. After surgery, combination chemotherapy with doxifluridine plus weekly paclitaxel was administered on an outpatient basis, and was effective without any sign of relapse of the disease for a year. However, she complained of dull abdominal pain, and ascites was observed 13 months after surgery. She received combination chemotherapy with S-1 plus weekly paclitaxel. The ascites decreased after 3 courses of the chemotherapy. No major adverse effect was observed except for grade 1 anemia and grade 2 hair loss. She has been well with the chemotherapy on an outpatient basis 18 months after surgery.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácido Oxônico/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Tegafur/uso terapêutico , Administração Oral , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Ácido Oxônico/administração & dosagem , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/cirurgia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Fluorouracil monotherapy, instead of the FOLFOX or FOLFIRI regimen, is administered to patients intolerant to oxaliplatin or irinotecan because of their adverse effects. A prospective clinical trial was designed to evaluate the efficacy and safety of fluorouracil monotherapy combined with panitumumab administered to patients with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) intolerant to oxaliplatin and irinotecan. Screening for potential serum biomarkers to predict early therapeutic responses was conducted. METHODS: This single-arm, open-label multicenter phase II trial recruited patients with KRAS WT mCRC from 16 institutes between January 2012 and October 2014. Panitumumab (6 mg/kg) was intravenously administered every 2 weeks, combined with fluorouracil monotherapy, in 2-week cycles. The primary objective was overall response rate, and secondary endpoints included disease-control rate, progression-free survival, overall survival, toxicity, and blood-test data. RESULTS: Forty patients (male, 65.0%; median age, 74 years; colon cancer, 72.5%) met eligibility criteria and received 7 cycles (median) of fluorouracil chemotherapy combined with panitumumab. There were no treatment-related deaths. Median time to treatment failure was 3.2 months. 23 (57.5%) patients experienced at least one adverse effect ≥ grade 3. The response rate was 10.0% (95% confidence interval 2.8-23.7%). Median progression-free survival and overall survival were 4.3 and 11.3 months, respectively. Total lactase dehydrogenase (LDH) levels and those of LDH-4 and LDH-5, quickly changed with disease reduction or progression. CONCLUSIONS: Fluorouracil monotherapy combined with panitumumab was safely administered to patients with KRAS WT mCRC intolerant to oxaliplatin and irinotecan. Serum LDH levels may predict early responses.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Panitumumabe/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Irinotecano/efeitos adversos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Oxaliplatina/efeitos adversos , Intervalo Livre de Progressão , Estudos Prospectivos , Falha de TratamentoRESUMO
BACKGROUND: The aim of this single-arm phase II clinical trial was to evaluate whether the alternate-day administration of S-1 plus irinotecan would reduce the incidence of severe diarrhea in comparison to consecutive-day S-1 administration (standard IRIS regimen) in second-line treatment for patients with metastatic colorectal cancer. METHODS: Patients with metastatic colorectal cancer after failure with first-line treatment of oxaliplatin and fluoropyrimidine were enrolled. Irinotecan (150 mg/m2) and bevacizumab (5 mg/kg) were given intravenously on day 1. Oral S-1 was administered on alternate days at a dose of 40-60 mg twice a day. Cycles were repeated every 2 weeks. The primary endpoint was the incidence of grade ≥ 3 diarrhea. Our hypothesis set 21% as a threshold incidence and 10% as an expected incidence from previous studies with one-sided alpha 0.05. The secondary endpoints included the relative dose intensity, progression-free survival, overall survival and other adverse events. RESULTS: A total of 51 patients were enrolled. The incidence of grade ≥ 3 diarrhea was 15.7% (8/51). Other common grade ≥ 3 adverse events were neutropenia, anemia, thrombocytopenia and fatigue were 13.7% (7/51), 5.9% (3/51), 2.0% (1/51) and 5.9% (3/51), respectively. The relative dose intensities of irinotecan, bevacizumab, and S-1 were 80.0, 86.8, and 77.7%, respectively. The median progression-free survival and overall survival were 8.4 months (5.8-9.8) and 17.1 months (11.8-22.3). CONCLUSIONS: The alternate-day S-1 administration does not have significant effectiveness to reduce diarrhea in patients who received second-line treatment for metastatic colorectal cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Diarreia/induzido quimicamente , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Neoplasias Colorretais/patologia , Diarreia/epidemiologia , Intervalo Livre de Doença , Esquema de Medicação , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Incidência , Irinotecano/administração & dosagem , Masculino , Metástase Neoplásica , Ácido Oxônico/administração & dosagem , Taxa de Sobrevida , Tegafur/administração & dosagemRESUMO
BACKGROUND: Orotate phosphoribosyl transferase (OPRT) is an essential enzyme for activation of 5-fluorouracil (5-FU) and its derivatives. Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme for degradation of 5-FU. In colorectal cancer (CRC), few studies have evaluated the relationship between OPRT, DPD, and clinicopathologic features. METHODS: The study included 150 patients whose CRCs were classified into stage II to IV, and resected operatively. OPRT and DPD expression were evaluated using immunohistochemistry with new antibodies. Relationships between their expressions and clinicopathologic features. Survival curves were calculated using Kaplan-Meier method, and differences were evaluated with log-rank test. Cox proportional hazards model was also used. RESULTS: OPRT expression showed a negative correlation with advances in venous invasion (P=.041), though DPD expression showed positive correlations with advances in venous invasion (P=.0053), and cancer stage (P=.0064). The patients survival rates were higher in those OPRT(+) than in those OPRT(-) (P=.004), and higher in those DPD(-) than in those DPD(+) (P=.008). The estimated hazard ratio for patients death with OPRT and DPD expression were 2.43 and 6.55 (P=.0047 and .0096) respectively. CONCLUSIONS: OPRT expression was associated negatively with CRC progression and related with better prognosis, although DPD expression was positively correlated with CRC progression and related with poor prognosis. The overall patients survival rates were best in the patients OPRT(+)DPD(-), and worst in those OPRT(-)DPD(+) in treatment with fluoropyrimidine after operation.