RESUMEN
BACKGROUND: Accelerated tumor growth during immunotherapy in pre-existing measurable lesions, hyperprogressive disease (HPD), has been reported. However, progression of non-measurable lesions and new lesions are frequently observed in patients with advanced gastric cancer (AGC). METHODS: This retrospective study involved AGC patients at 24 Japanese institutions who had measurable lesions and received nivolumab after ≥ 2 lines of chemotherapy. HPD was defined as a ≥ two-fold increase in the tumor growth rate of measurable lesions. The pattern of disease progression was classified according to new lesions in different organs and ascites appeared/increase of ascites. RESULTS: Of 245 patients, 147 (60.0%) showed progressive disease (PD) as the best response and 41 (16.7%) showed HPD during nivolumab monotherapy. There was no significant difference in overall survival (OS) between patients with HPD and those with PD other than HPD (median OS 5.0 vs 4.8 months; hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.6-1.5; p = 1.0). Fifty-three patients developed new lesions in different organs and 58 had appearance/increase of ascites; these patients showed shorter OS than those without each of these features (median OS 3.3 vs 7.1 months, HR 1.8, 95% CI 1.2-2.7, p = 0.0031 for new lesions, and 3.0 vs 7.8 months, HR 2.6, 95% CI 1.8-3.8, p < 0.0001 for ascites). Thirty-one patients who had both features showed the worst prognosis (median OS 2.6 months). CONCLUSIONS: New lesions in different organs and appearance/increase of ascites, rather than the original definition of HPD, are the patterns of disease progression associated with poor prognosis in AGC patients receiving nivolumab whose best response was PD.
Asunto(s)
Nivolumab , Neoplasias Gástricas , Humanos , Nivolumab/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Estudios Retrospectivos , Japón , Ascitis , Pronóstico , Progresión de la EnfermedadRESUMEN
BACKGROUND: The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. MATERIALS AND METHODS: DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). RESULTS: Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, p = .07). FOLFIRI showed a trend toward better response rate (RR), progression-free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p = .134 for RR; interaction test, p = .102 for PFS and p = .003 for OS) and 8q24.2 (Fisher's exact test, p = .179 for RR; interaction test, p = .144 for PFS and p = .002 for OS). CONCLUSION: Chromosome 8q24.1-q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. IMPLICATIONS FOR PRACTICE: Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1-p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.
Asunto(s)
Bevacizumab/uso terapéutico , Biomarcadores/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Hibridación Genómica Comparativa/métodos , Irinotecán/uso terapéutico , Oxaliplatino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/farmacología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Humanos , Irinotecán/farmacología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Oxaliplatino/farmacología , Pronóstico , Análisis de SupervivenciaRESUMEN
A 69-year-old man with chronic gastritis, reflux esophagitis, esophageal hiatal hernia, and history of appendicitis surgery complained of difficulty swallowing. Upper gastrointestinal endoscopy revealed a 10 cm sized Type 3 gastric cancer. Immunostaining was positive for chromogranin A(2+), synaptophysin(3+), CD56(-), and Ki-67>70%. Contrast computed tomography(CT)showed upper gastric wall thickening, and #1, #3, #7, #8a, and #11p enlarged lymph nodes but no distant metastasis. We diagnosed gastric cancer, UM, Less, Type 3, gastric neuroendocrine carcinoma, cT4aN3M0P0CY0, Stage â ¢C. We administered 2 courses of CDDP plus CPT-11 chemotherapy, and a partial response was obtained for the primary gastric lesion and lymph node metastases. We subsequently performed open distal gastrectomy, D2 lymph node dissection, and splenectomy. Pathological examination confirmed that the lesion was gastric cancer, U, Less, Type 3, gastric neuroendocrine carcinoma, MP, Ul-â ¡(+), int, INF b, ly2, v0, PM0, DM0, R0, ypT2N2, Stage â ¡B, with a therapeutic value of Grade 2. The patient was discharged on day 15 after the surgery and received 2 courses of adjuvant chemotherapy with CDDP plus CPT-11. Nine months after the surgery, metastasis of the left adrenal grand was found. We performed open left adrenal gland resection and administered adjuvant S-1 chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Neuroendocrino , Neoplasias Gástricas , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Neuroendocrino/tratamiento farmacológico , Cisplatino/administración & dosificación , Combinación de Medicamentos , Gastrectomía , Humanos , Irinotecán/administración & dosificación , Metástasis Linfática , Masculino , Ácido Oxónico , Neoplasias Gástricas/tratamiento farmacológico , TegafurRESUMEN
BACKGROUND: Fluoropyrimidine and platinum combination is the standard treatment for advanced or recurrent gastric cancer (AGC). However, fluoropyrimidine monotherapy is commonly used for elderly patients with AGC because of its good tolerability. METHODS: In this multicenter retrospective study, we collected clinical data of AGC patients aged 70 years or older, treated with S-1 alone or S-1 plus cisplatin (SP) as the first-line treatment between January 2009 and December 2011. Propensity score matched cohorts (PSMC) were used for reducing the confounding effects to compare efficacy and safety between the two treatment groups. Cox regression analysis was performed to clarify the prognostic factors. RESULTS: PSMC (n = 109 in each group) were selected from among 444 eligible patients (S-1 group, 210; SP group, 234); the S-1 group included more patients deemed unfit for intensive chemotherapy than the SP group (e.g., higher age, poorer PS, poor renal function). In the PSMC, patients' characteristics were comparable between groups, except the male ratio (S-1 group, 64.2%; SP group, 77.1%; p = 0.04). No significant differences were observed in either overall survival [hazard ratio (HR) 0.93, p = 0.63] or progression-free survival (HR 1.09, p = 0.61). Severe adverse events (AEs) and hospitalization due to AEs were more frequent in the SP group than in the S-1 group (p < 0.001 each). CONCLUSION: Our findings do not support the survival benefit of SP over S-1 in elderly patients with AGC. We are now conducting a prospective comparative study to optimize treatment strategy and explore applicability of the geriatric assessment for these patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Combinación de Medicamentos , Femenino , Humanos , Masculino , Análisis Multivariante , Ácido Oxónico/administración & dosificación , Ácido Oxónico/uso terapéutico , Puntaje de Propensión , Neoplasias Gástricas/patología , Tegafur/administración & dosificación , Tegafur/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Although number of elderly patients with metastatic colorectal cancer (mCRC) is rapidly increasing, this population is often underrepresented in clinical trials. Recently, a phase II trial demonstrated that capecitabine and oxaliplatin (XELOX) combined with bevacizumab XELOX plus bevacizumab was effective and well tolerated by elderly patients with mCRC who reside in Western countries. The aim of this study was to evaluate the safety and efficacy of XELOX plus bevacizumab for Japanese patients aged ≥ 75 years with mCRC. METHODS: This prospective, open-label phase II trial recruited patients aged ≥ 75 years with previously untreated mCRC between March 2010 and January 2012. Treatment consisted of 7.5 mg/kg of intravenous bevacizumab and 130 mg/m(2) of oxaliplatin on day 1 of each cycle combined with 2000 mg/m(2) of oral capecitabine per day on days 1-14 of each cycle. Treatment was repeated every 3 weeks until disease progression or termination of the study. The primary endpoint was progression-free survival; the secondary endpoints were toxicity, overall response rate, time-to-treatment failure, and overall survival. RESULTS: Thirty-six patients (male 58%; median age 78 years; colon cancer 67%) met all eligibility criteria and received at least one course of the planned treatment. The median time-to-treatment failure was 7.0 months. Twelve patients (33.3%) experienced adverse effects (AEs) ≥ grade 3 and frequent AEs ≥ grade 3, including neutropenia (22.2%) and neuropathy (13.9%). Hypertension was the most frequent AE ≥ grade 3 associated with bevacizumab (11.1%). Low baseline creatinine clearance associated significantly with the incidence of AEs ≥ grade 3. Response and disease control rates were 55.6 and 91.7%, respectively. Median progression-free and overall survival times were 11.7 months (95% confidence interval, 8.0-13.4 months) and 22.9 months, respectively. CONCLUSION: XELOX combined with bevacizumab was well tolerated by selected Japanese patients aged ≥ 75 years with mCRC patients, and controlled clinical trials are now required to determine the survival benefit.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Pueblo Asiatico , Bevacizumab/administración & dosificación , Capecitabina/administración & dosificación , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/tratamiento farmacológico , Compuestos Organoplatinos/administración & dosificación , Factores de Edad , Anciano , Anciano de 80 o más Años , Bevacizumab/efectos adversos , Capecitabina/efectos adversos , Neoplasias Colorrectales/mortalidad , Femenino , Humanos , Masculino , Náusea/inducido químicamente , Neutropenia/inducido químicamente , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Estudios Prospectivos , Tasa de Supervivencia/tendencias , Resultado del TratamientoRESUMEN
The combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) as preoperative treatment for esophageal squamous cell carcinoma (ESCC) has not been investigated. We carried out a multicenter phase II feasibility study of preoperative chemotherapy with DCF for ESCC. Patients with clinical stage II/III ESCC (International Union Against Cancer TNM classification system, 6th edition) were eligible. Chemotherapy consisted of i.v. docetaxel (70-75 mg/m(2)) and cisplatin (70-75 mg/m(2)) on day 1, and continuous infusion of fluorouracil (750 mg/m(2)/day) on days 1-5. Antibiotic prophylaxis on days 5-15 was mandatory. This regimen was repeated every 3 weeks with a maximum of three cycles allowed. After completion of chemotherapy, esophagectomy with extended lymphadenectomy was carried out. The primary endpoint was the completion rate of protocol treatment. Forty-two eligible patients were enrolled. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (83%), anorexia (7%), and stomatitis (5%). Forty-one (98%) patients underwent surgery. The completion rate of protocol treatment was 90.5% (38/42). No treatment-related death was observed and the incidence of operative morbidity was tolerable. According to RECIST, the overall response rate after the completion of DCF was 64.3%. Pathological complete response was achieved in 17%. The estimated 2-year progression-free survival and overall survival were 74.5% and 88.0%, respectively. Although these data are preliminary, preoperative DCF was well tolerated. Antitumor activity was highly promising and warrants further investigation. This trial was registered with University Hospital Medical Information Network (no. UMIN000002396).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Docetaxel , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Estudios de Factibilidad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Taxoides/administración & dosificación , Toracotomía , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: To evaluate the efficacy of internal biliary drainage after pancreaticoduodenectomy (PD), postoperative gastrointestinal function and complications of PD were compared in patients with and without the use of an external drainage stent for hepaticojejunostomy (HJ). METHODOLOGY: Between June 2005 and September 2011, 66 patients who underwent PD, including 40 patients with externally-stented HJ (ES group) and 26 patients with non-stented HJ (NS group), were included in this study, and postoperative bowel movements, oral intake, and complications were assessed. RESULTS: Time to tolerance of water or solid food were comparable between the two groups, and time to first bowel movement was significantly shorter in the NS group than in the ES group (3.2 +/- 1.6 days versus 4.6 +/- 1.7 days; p = 0.002). There were no differences in the incidence and severity of postoperative complications when comparing the two groups, whereas the incidence of postoperative cholangitis was significantly higher in the ES group (25.0%) than in the NS group (3.8%; p = 0.024). CONCLUSIONS: External biliary drainage may have a negative impact on biliary complications after PD, especially on the incidence of postoperative cholangitis.
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Drenaje , Ictericia Obstructiva/cirugía , Pancreaticoduodenectomía/efectos adversos , Anciano , Colangitis/epidemiología , Drenaje/instrumentación , Femenino , Humanos , Incidencia , Japón/epidemiología , Yeyunostomía/efectos adversos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Stents , Factores de Tiempo , Resultado del TratamientoRESUMEN
This phase II, open-label, single-arm study investigated sunitinib + FOLFIRI in Japanese patients with treatment-naïve unresectable/metastatic colorectal cancer. Patients received i.v. FOLFIRI (levo-leucovorin 200 mg/m(2) + irinotecan 180 mg/m(2), followed by 5-fluorouracil 400 mg/m(2) bolus then 2400 mg/m(2) 46-h infusion) every 2 weeks, and oral sunitinib 37.5 mg/day on Schedule 4/2 (4 weeks on, 2 weeks off), until disease progression or treatment withdrawal. Progression-free survival (PFS) was the primary endpoint, with a target median of 10.8 months (35% improvement over FOLFIRI alone). Seventy-one patients started a median of 3 (range 1-11) sunitinib cycles (median relative dose intensity, <60%). The median PFS was 6.7 months (95% confidence interval, 4.7-9.2) by independent review, 7.2 months (95% confidence interval, 5.4-9.5) by investigator assessment. Objective response rate (complete responses + partial responses) was 36.6% (independent review) and 42.3% (investigator assessment). Clinical benefit rate (complete responses + partial responses + stable disease) was 83.1% (independent review) and 88.7% (investigator assessment). Common all-causality, any-grade, adverse events were: neutropenia and leukopenia (both 97.2%); thrombocytopenia (84.5%); diarrhea and nausea (both 78.9%); decreased appetite (74.6%); and fatigue (66.2%). Neutropenia (96%) was the most frequent grade 3/4 adverse event. This study was closed early due to findings from a concurrent phase III study of sunitinib + FOLFIRI in non-Japanese patients with metastatic colorectal cancer. In conclusion, the median PFS for sunitinib + FOLFIRI in Japanese patients was shorter than the 10.8 month target, indicating that sunitinib did not add to the antitumor activity of FOLFIRI. This study was registered with www.ClinicalTrials.gov (NCT00668863).
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Indoles/administración & dosificación , Pirroles/administración & dosificación , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Pueblo Asiatico , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Humanos , Indoles/efectos adversos , Leucovorina/efectos adversos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pirroles/efectos adversos , Sunitinib , Resultado del TratamientoRESUMEN
BACKGROUND: When applying the topoisomerase inhibitor irinotecan (CPT) with the infusional fluorouracil/levofolinate (FOLFIRI) ± bevacizumab chemotherapy regimen in cases of advanced colorectal carcinoma, the international standard dose for CPT is 180 mg/m(2). Despite this, 150 mg/m(2) CPT is widely prescribed and is the maximum dosage covered by Japanese health insurance. Consequently, the safety of dosing at the international standard has not been tested comprehensively and the efficacy of FOLFIRI in Japan may be underestimated. METHODS: To evaluate the safety of FOLFIRI (+bevacizumab) in clinical practice using international standards, we reviewed medical records of 53 patients who received FOLFIRI (+bevacizumab) with CPT 180 mg/m(2) as first-line treatment between September 2004 and August 2009. The primary endpoint of the study was to measure the relative dose intensity (RDI) of CPT after four courses. The secondary endpoint was to assess treatment completion rate, adverse events, response rate, progression-free survival (PFS) and overall survival (OS) among all patients. RESULTS: The RDI and the treatment completion rate were 88.9% and 69.8%, respectively, in the 53 patients. Accompanying grade 3 or 4 adverse events included neutropenia (35.8%), febrile neutropenia (7.5%), and diarrhea (3.8%). Supportive care managed all toxicity symptoms. Median durations for PFS and OS were 10.3 and 26.5 months, respectively. CONCLUSION: FOLFIRI (+bevacizumab) with the international standard dose of CPT is feasible in clinical practice. In order to minimize deviation of the Japanese regimen from global best practice, international dose standards should be followed.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Japón , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neutropenia/inducido químicamente , Estudios RetrospectivosRESUMEN
Between 1989 and 2009, 10 patients with small bowel adenocarcinoma were treated in our hospital. These tumors appeared in the jejunum in 6 patients and in the ileum in the remaining 4 patients. All patients had some symptoms. The median size of the tumors was 50mm(30-110mm). All tumors were advanced type 2 lesion with severe stricture. Histologically there were 8 well, 1 moderately and 1 poorly differentiated adenocarcinomas. There were 8 tumors invading the serosa and 2 tumors invaded other organs. Positive lymph nodes were identified in 6 cases. Liver metastasis and peritoneal dissemination were identified in 3 and 4 cases, respectively. Eight cases were diagnosed as small bowel adenocarcinoma preoperatively by double balloon endoscopy. The 4 patients with stage II tumor and 2 patients with stage III tumor underwent curative-intent surgery. The 4 patients with stage II tumor are all surviving without evidence of disease now.
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Adenocarcinoma/patología , Neoplasias del Íleon/patología , Neoplasias del Yeyuno/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: This study examined the effect of five systemic chemotherapy regimens on survival in patients with unresectable biliary tract cancer (BTC) as compared with the best supportive care (BSC). METHODS: This study retrospectively reviewed data from 413 consecutive patients with BTC who were seen at any of nine central hospitals in Japan between April 2000 and March 2003. Patients were eligible if they had intra- or extrahepatic cholangiocarcinoma or gallbladder cancer with no prior chemotherapy. Hazard ratios of treatment regimens were estimated using the Cox proportional hazard model and the propensity score method. RESULTS: Three-hundred and four patients were enrolled: 125 (41.1%) received BSC and 179 (58.9%) took chemotherapy. Of those who received chemotherapy, 58 (19.1%) took gemcitabine (GEM), 45 (14.5%) took a cisplatin (CDDP)-based regimen, 30 (9.9%) took a 5-fluorouracil (5-FU)-based regimen, 27 (8.9%) took 5-FU + doxorubicin + mitomycin (FAM) and 20 (6.6%) took S-1. The response rate was 8.4% (n = 15). The CDDP-based regimen was associated with a high frequency of toxicity symptoms. The adjusted hazard ratio for GEM in the Cox regression was 0.53 (95% CI 0.34-0.82) and the hazard ratio for the CDDP-based regimen was 0.49 (95% CI 0.36-0.99). CONCLUSION: Chemotherapy with GEM may benefit patients with BTC.
Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/mortalidad , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Doxorrubicina/administración & dosificación , Combinación de Medicamentos , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Ácido Oxónico/administración & dosificación , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Supervivencia , Tegafur/administración & dosificación , GemcitabinaRESUMEN
BACKGROUND/AIMS: Hypofractionated radiotherapy can shorten the irradiation period and allow systemic chemotherapy with full-dose gemcitabine to be started earlier. The purpose of this study was to determine the feasible dose of hypofractionated radiotherapy that could be followed by full-dose gemcitabine in patients with locally advanced pancreatic cancer. METHODOLOGY: Nine patients with unresectable locally advanced pancreatic cancer were enrolled in this study. Three patients received radiotherapy at 45Gy in 15 fractions (level 1) and six at 40 Gy in 8 fractions (level 2). Systemic chemotherapy with gemcitabine was started 3 months after the start of irradiation and was administered as a 30-minute intravenous infusion of a dose of 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. RESULTS: No patients experienced dose-limiting toxicity at either level of radiotherapy. Gemcitabine was started in two of the three patients treated at the level 1 on schedule. At level 2, grade 3 nausea, vomiting and anorexia was observed in all 6 patients, and gemcitabine could not be started on schedule in 4 of the 6 patients. Two (22%) of the 9 patients achieved a partial response. The median time to progression was 5.8 months and the median overall survival time was 9.5 months. CONCLUSIONS: Hypofractionated radiotherapy with 40 Gy in 8 fractions was not feasible in patients with locally advanced pancreatic cancer.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Desoxicitidina/análogos & derivados , Fraccionamiento de la Dosis de Radiación , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Anciano , Terapia Combinada , Desoxicitidina/administración & dosificación , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , GemcitabinaRESUMEN
PURPOSE: To evaluate the safety and efficacy of proton beam radiotherapy (PRT) for hepatocellular carcinoma. PATIENTS AND METHODS: Eligibility criteria for this study were: solitary hepatocellular carcinoma (HCC); no indication for surgery or local ablation therapy; no ascites; age >/= 20 years; Zubrod performance status of 0 to 2; no serious comorbidities other than liver cirrhosis; written informed consent. PRT was administered in doses of 76 cobalt gray equivalent in 20 fractions for 5 weeks. No patients received transarterial chemoembolization or local ablation in combination with PRT. RESULTS: Thirty patients were enrolled between May 1999 and February 2003. There were 20 male and 10 female patients, with a median age of 70 years. Maximum tumor diameter ranged from 25 to 82 mm (median, 45 mm). All patients had liver cirrhosis, the degree of which was Child-Pugh class A in 20, and class B in 10 patients. Acute reactions of PRT were well tolerated, and PRT was completed as planned in all patients. Four patients died of hepatic insufficiency without tumor recurrence at 6 to 9 months. Three of these four patients had pretreatment indocyanine green retention rate at 15 minutes of more than 50%. After a median follow-up period of 31 months (16 to 54 months), only one patient experienced recurrence of the primary tumor, and 2-year actuarial local progression-free rate was 96% (95% CI, 88% to 100%). Actuarial overall survival rate at 2 years was 66% (48% to 84%). CONCLUSION: PRT showed excellent control of the primary tumor, with minimal acute toxicity. Further study is warranted to scrutinize adequate patient selection in order to maximize survival benefit of this promising modality.
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Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Radioterapia/métodos , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/mortalidad , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Cirrosis Hepática/clasificación , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Radioterapia/efectos adversos , Tasa de SupervivenciaRESUMEN
Little is known about the clinical impact of salvage panitumumab with irinotecan for metastatic colorectal cancer (mCRC) patients. The present study conducted a single-arm, multicenter phase II trial for mCRC with skin toxicity prevention program. The subjects were mCRC patients with wild-type KRAS, who showed resistance to fluoropyrimidine, oxaliplatin and irinotecan. Panitumumab was administered at a dose of 6 mg/kg every 2 weeks by intravenous infusion over 60 min, and irinotecan was administered at a dose of 100-180 mg/m2 every 2 weeks by intravenous infusion over 90 min, depending on the preceding treatment dose. To prevent skin toxicities, a moisturizer was applied and oral antibiotics (100 mg minocycline twice daily) were initiated for 6 weeks. The primary endpoint was the response rate (RR) determined by independent reviewers. Secondary endpoints were the disease control rate (DCR), progression-free survival (PFS) time, overall survival (OS) time and adverse events. A total of 35 patients were enrolled between October 2010 and March 2012. The median age was 61 years (range, 41-76 years), with 25 male and 10 female patients. The initial irinotecan dose was 150 mg/m2 in 19 patients and 180 mg/m2 in 1 patient. The remaining patients were treated with ≤120 mg/m2. A central review indicated a partial response in 8 patients (22.9%) and stable disease in 6 patients (17.1%), with an RR of 22.9% (95% confidence interval, 12.1-39.0) and a DCR of 40%. The RR of the patients with standard-dose irinotecan (150 or 180 mg/m2) was 30%, although that of low-dose irinotecan (100-120 mg/m2) was 13%. The median PFS time was 2.7 months, and the median OS time was 6.3 months. A grade 3 or above acne-like rash developed in 25.7% of patients. In conclusion, panitumumab and irinotecan as salvage therapy for mCRC KRAS wild-type patients with skin toxicity prevention exhibits limited efficacy. In particular, the effect of low-dose irinotecan with panitumumab appears to be clinically insignificant. Routine use of skin toxicity prevention is currently under evaluation.
RESUMEN
BACKGROUND/AIMS: To clarify whether external beam radiotherapy combined with intraluminal brachytherapy without stenting provides long-term relief of jaundice in extrahepatic cholangiocarcinoma patients. METHODOLOGY: Twenty-five patients with unresectable hilar or distal cholangiocarcinoma were treated by external beam radiotherapy (30 or 50 Gy) combined with intraluminal brachytherapy (24 to 40 Gy). After radiotherapy, we removed the biliary drainage tubes from the patients who responded, and we did not perform stenting in these patients. RESULTS: In 19 (76%) patients, full patency was achieved at the treated lesion, and they were tube-free thereafter. The tube-free survival time in the 19 patients ranged from 7 to 468 days (median: 76 days). Cholangitis and gastroduodenal ulcer developed in 10 (40%) and 2 (8%) patients, respectively, as adverse events after the combined radiotherapy. The median survival time of all patients was 9.3 months, and their 6- and 12-month survival rates were 75.3% and 29.3%, respectively. The ratios of tube-free to overall survival in the 19 patients ranged from 2.4% to 79.4% (median: 26.8%). Eight patients died tube-free. CONCLUSIONS: Although there were limitations to the long-term relief of jaundice by this combined radiotherapy alone, tube-free status was achieved in some patients without stenting.
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Neoplasias de los Conductos Biliares/complicaciones , Conductos Biliares Extrahepáticos , Braquiterapia/métodos , Colangiocarcinoma/complicaciones , Ictericia Obstructiva/etiología , Ictericia Obstructiva/radioterapia , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/mortalidad , Braquiterapia/efectos adversos , Colangiocarcinoma/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Stents , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: To examine the efficacy and safety of a combined modality therapy consisting of hepatic arterial infusion of 5-fluorouracil and external-beam radiotherapy in patients with advanced pancreatic carcinoma. METHODOLOGY: Hepatic arterial infusion chemotherapy consisted of 5-FU 1000mg/m2 administrated as a 5-hr continuous infusion once weekly. External-beam radiotherapy (total dose, 50Gy; 2Gy/day) was delivered to the pancreas tumor concurrently for 5-6 weeks. Seventeen patients with no distant metastases except to the liver were enrolled in this study. RESULTS: Patients received a median of 13 cycles of chemotherapy. Sixteen of 17 patients received a total radiotherapy dose of 50Gy. In one patient, treatment was discontinued after 24Gy of radiotherapy and 2 cycles of chemotherapy because of progressive disease. Nausea and vomiting were the most common types of toxicity. Grade 3 or worse toxicity was observed in 2 patients. Four patients developed gastroduodenal ulcers. Of the 16 patients, 7 (41%) showed a partial response, and 9 (53%) showed no change. The median overall survival was 4.5 months and 1-yr overall survival of 11.8% was observed. CONCLUSIONS: The combined therapy is active and well tolerated, but results in a poorer prognosis, in spite of its high initial response rate.
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Antimetabolitos Antineoplásicos/administración & dosificación , Carcinoma/radioterapia , Carcinoma/secundario , Fluorouracilo/administración & dosificación , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundario , Neoplasias Pancreáticas/patología , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Carcinoma/tratamiento farmacológico , Carcinoma/mortalidad , Terapia Combinada , Relación Dosis-Respuesta en la Radiación , Femenino , Fluorouracilo/efectos adversos , Arteria Hepática , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Traumatismos por Radiación , Análisis de SupervivenciaRESUMEN
BACKGROUND/AIMS: Virtual endoscopy is a new method of diagnosis using computer processing of three-dimensional images data sets. However, there are few reports about the clinical application of virtual endoscopy for the pancreas. In this study, we evaluated the feasibility of surface-rendered magnetic resonance virtual endoscopy for pancreatic cancer. METHODOLOGY: Twenty-six cases of pancreatic cancer were studied. Fifteen patients had pancreatic head cancer, 7 had pancreatic body cancer, and 4 had pancreatic tail cancer. Twelve patients underwent surgical resection of the pancreas. Magnetic resonance imaging data were acquired with a 1.5-T clinical imager (Signal.5; GE Medical Systems, USA). We used a multislab single-shot fast spin-echo sequence. Section thickness was between 2 and 3 mm in the coronal plane. Three-dimensional reconstructed images and virtual endoscopic images were generated with Advantage Windows by GE. RESULTS: Virtual endoscopic images could be generated in 20 patients with pancreatic cancer (76.9%). In these cases, we were able to observe the inner surface of the pancreatic duct and the stricture from not only the pancreatic head but also the pancreatic tail. Clear virtual images could not be generated in 6 cases. We were able to divide the 20 cases in which images could be generated into groups according to the appearance of the stricture. The edge of the stricture appeared to be protruding in 4 cases (15.4%), and appeared to be polygonal in 13 cases (50.0%). In 3 cases, we recognized the existence of a stricture, but the detail of the stricture was unclear. CONCLUSIONS: Virtual endoscopy caused minimal discomfort compared to real endoscopic examination, and it can access cystic lesions and the pancreatic duct behind the stricture. It is concluded that virtual endoscopy for pancreatic cancer has potential clinical utility.
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Endoscopía del Sistema Digestivo/métodos , Neoplasias Pancreáticas/diagnóstico , Anciano , Anciano de 80 o más Años , Artefactos , Constricción Patológica , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Conductos Pancreáticos/patología , Interfaz Usuario-ComputadorRESUMEN
PURPOSE: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). METHODS AND MATERIALS: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m2 twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m2/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. RESULTS: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of ≥100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. CONCLUSIONS: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.
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Adenocarcinoma/terapia , Antimetabolitos Antineoplásicos/administración & dosificación , Carcinoma Adenoescamoso/terapia , Quimioradioterapia/métodos , Ácido Oxónico/administración & dosificación , Neoplasias Pancreáticas/terapia , Tegafur/administración & dosificación , Adenocarcinoma/sangre , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Antígeno CA-19-9/sangre , Carcinoma Adenoescamoso/sangre , Carcinoma Adenoescamoso/mortalidad , Carcinoma Adenoescamoso/patología , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Japón , Quimioterapia de Mantención/métodos , Masculino , Persona de Mediana Edad , Ácido Oxónico/efectos adversos , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Tasa de Supervivencia , Tegafur/efectos adversosRESUMEN
PURPOSE: This phase III study compared treatment with weekly paclitaxel and biweekly irinotecan in patients with advanced gastric cancer refractory to treatment with fluoropyrimidine plus platinum. PATIENTS AND METHODS: Patients were randomly assigned to receive either paclitaxel (80 mg/m(2) on days 1, 8, and 15, every 4 weeks) or irinotecan (150 mg/m(2) on days 1 and 15, every 4 weeks). Primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), response rate, adverse events, and proportion of patients who received third-line chemotherapy. RESULTS: Of 223 patients, 219 were eligible for analysis. Median OS was 9.5 months in 108 patients allocated to the paclitaxel group and 8.4 months in 111 patients allocated to the irinotecan group (hazard ratio [HR], 1.13; 95% CI, 0.86 to 1.49; P = .38). Median PFS was 3.6 months in the paclitaxel group and 2.3 months in the irinotecan group (HR, 1.14; 95% CI, 0.88 to 1.49; P = .33). Response rate was 20.9% in the paclitaxel group and 13.6% in the irinotecan group (P = .24). Common grade 3 to 4 adverse events were neutropenia (paclitaxel group, 28.7%; irinotecan group, 39.1%), anemia (21.3%; 30.0%), and anorexia (7.4%; 17.3%). Treatment-related deaths occurred in two patients (1.8%) in the irinotecan group. Third-line chemotherapy was administered in 97 patients (89.8%) after paclitaxel treatment and in 80 patients (72.1%) after irinotecan treatment (P = .001). CONCLUSION: No statistically significant difference was observed between paclitaxel and irinotecan for OS. Both are reasonable second-line treatment options for advanced gastric cancer.
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Camptotecina/análogos & derivados , Paclitaxel/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anemia/inducido químicamente , Anorexia/inducido químicamente , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Irinotecán , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Paclitaxel/efectos adversos , Platino (Metal)/administración & dosificación , Estudios Prospectivos , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
Metastasis in the liver is one of the most critical factors in the prognosis of patients with colorectal cancer. The incidence of synchronous liver metastasis has been found to be approximately 20-25%, but the optimal timing of surgical resection remains controversial. Neoadjuvant chemotherapy has also been found to be beneficial not only for initially unresectable but also resectable synchronous metastases and traditional surgical strategies of hepatic resection with past chemotherapeutic regimens have been used less and less over the past several years. This review will discuss treatments in association with the recently developed chemotherapeutic regimens.