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BACKGROUND: Zoledronic acid (ZA) reduces the incidence of skeletal-related events (SREs) in patients with bone metastases from solid tumors. However, the optimal dosing interval of ZA for patients with lung cancer is uncertain. METHODS: We conducted a randomized, open-label, feasibility phase 2 trial at eight Japanese hospitals. Patients with bone metastases from lung cancer were randomly assigned to receive either 4 mg of ZA every four weeks (4wk-ZA) or every eight weeks (8wk-ZA). The primary endpoint was the time to the first SRE and the rate and types of SREs after one year. SREs were defined as pathologic bone fracture, bone radiation therapy or surgery, and spinal cord compression. Secondary endpoints were the SRE incidence at six months, pain assessment, changes in analgesic consumption, serum N-telopeptide, toxicity, and overall survival. RESULTS: Between November 2012 and October 2018, 109 patients were randomly assigned to the 4wk-ZA group (54 patients) and the 8wk-ZA group (55 patients). The number of patients who received chemotherapy or molecular-targeted agents was 30 and 23 and 18 and 16 in the 4wk-ZA and 8wk-ZA groups, respectively. The median time to the first SRE could not be calculated because of a low SRE. The time to the first SRE of all patients did not differ between the groups (P = 0.715, HR = 1.18, 95% CI = 0.48, 2.9). The SRE rate of all patients after 12 months was 17.6% (95% CI = 8.4, 30.9%) in the 4wk-ZA and 23.3% (95% CI = 11.8, 38.6%) in the 8wk-ZA group, without significant differences between the groups. There was no difference in any secondary endpoint between groups, and these endpoints did not differ among treatment modalities. CONCLUSIONS: An eight-week ZA interval does not increase the SRE risk for patients with bone metastasis from lung cancer and could be considered clinically.
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Neoplasias Óseas , Neoplasias Pulmonares , Humanos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Ácido Zoledrónico/uso terapéuticoRESUMEN
High-grade myofibroblastic sarcoma is a rare mesenchymal tumor with a high recurrence and metastatic rate. Few cases of high-grade myofibroblastic sarcomas have been reported. Herein, we report a rare case of undifferentiated, high-grade myofibroblastic sarcoma with an unclear primary site, initially presenting with oral symptoms. High-grade myofibroblastic sarcoma was diagnosed following an excisional biopsy of a gingival tumor. After this excisional biopsy, systemic imaging revealed multiple metastases in the tonsil, lung, liver, kidney, and eye. The patient underwent two cycles of chemotherapy (doxorubicin). During follow-up, the tumor progressed rapidly and metastasized to the skin of the head and neck. The patient expired three months after the initial examination.
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Background/Aim: FOLFIRINOX (oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin) combination chemotherapy is the gold-standard therapy for advanced pancreatic cancer. In this study, FOLFIRINOX dosages for Japanese patients were established enabling FOLFIRINOX therapy optimization for efficient use. Patients and Methods: Patients with advanced pancreatic cancer were treated with varying doses of FOLFIRINOX to determine the optimum dosage for highest remission outcomes with the least post-chemotherapy toxicities. Results: Patients given 180 mg of irinotecan and a 400 mg bolus of 5-fluorouracil (5-FU) showed a marked difference in outcome when compared to irinotecan 180 mg given without the 5-FU bolus, with the overall response rate being 28%, a survival time of 6.4 months and progression-free survival time of 4.5 months. Conclusion: The optimum dose of FOLFIRINOX was a dosage combination of oxaliplatin 85 mg/m 2 , irinotecan 180 mg/m 2 , l-leucovorin 400 mg/m 2 and 5-FU 2,400 mg/m 2 , administered as a continuous 46-h infusion.
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OBJECTIVE: Many clinical trials for older patients with metastatic colorectal cancer have been conducted, and fluoropyrimidine and bevacizumab are standard treatments. However, the relationship between age and the efficacy and safety of this treatment is unclear in older metastatic colorectal cancer patients. METHODS: Individual data from two phase II studies on older (≥75 years), non-frail patients with metastatic colorectal cancer treated with uracil-tegafur/leucovorin or S-1 combined with bevacizumab were collected. Patient characteristics were evaluated with multiple regression analyses for survival outcomes, using the Cox proportional hazard model and linear regression analyses for the worst grade of adverse events. RESULTS: We enrolled 102 patients with a median age of 80 years (range, 75-88 years). Of the 70 patients who died, seven (10%) died of causes unrelated to disease or treatment. The study treatment was discontinued due to adverse events in 19 patients (18.6%), with 63% aged ≥85 years. The adverse event that most commonly resulted in treatment discontinuation was grade 2 fatigue (21%). Chronological age was not associated with progression-free survival (Hazard ratio, 1.03; P = 0.40) or overall survival (Hazard ratio, 1.02; P = 0.65). Age was weakly associated with non-hematologic adverse events (regression coefficient [R], 0.27; P = 0.007), especially fatigue (R, 0.23; P = 0.02) and nausea (R, 0.19; P = 0.06), but not with hematologic (R, 0.05; P = 0.43) or bevacizumab-related (R, -0.06; P = 0.56) adverse events. CONCLUSIONS: The efficacy of fluoropyrimidine plus bevacizumab was age-independent in patients with metastatic colorectal cancer aged ≥75 years, and attention should be paid to non-hematologic adverse events as age increases.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Fatiga/etiología , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/efectos adversos , Neoplasias del Recto/tratamiento farmacológicoRESUMEN
BACKGROUND: Primary tumor location (PTL) is an important prognostic and predictive factor in the first-line treatment of metastatic colorectal cancer (mCRC). Although regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) have been introduced recently, the clinical impact of PTL in these treatments is not well understood. MATERIALS AND METHODS: We retrospectively evaluated patients with mCRC who were registered in a multicenter observational study (the REGOTAS study). The main inclusion criteria were Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2, refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, angiogenesis inhibitors, anti-epidermal growth factor receptor therapy (if RAS wild-type), and no prior use of REG and FTD/TPI. The impact of PTL on overall survival (OS) was evaluated using Cox proportional hazard models based on baseline characteristics. RESULTS: A total of 550 patients (223 patients in the REG group and 327 patients in the FTD/TPI group) were included in this study, with 122 patients with right-sided tumors and 428 patients with left-sided tumors. Although the right-sided patients had significantly shorter OS compared with the left-sided patients by univariate analysis (p = 0.041), a multivariate analysis revealed that PTL was not an independent prognostic factor (hazard ratio, 0.95; p = 0.64). In a subgroup analysis, the OS was comparable between the REG and FTD/TPI groups regardless of PTL (p for interactions = 0.60). CONCLUSIONS: In the present study, PTL is not a prognostic and predictive factor in patients with mCRC under later-line REG or FTD/TPI therapy.
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BACKGROUND/AIM: In later-line treatment of metastatic colorectal cancer (mCRC), trifluridine/tipiracil is often selected because regorafenib is difficult to use in patients with comorbidities such as thrombosis, hemorrhage, or cardiac events. However, the safety and efficacy of trifluridine/tipiracil in these patients is not clear. PATIENTS AND METHODS: The clinical outcomes of trifluridine/tipiracil were retrospectively investigated in patients who were ineligible for regorafenib because of comorbidities. RESULTS: Among the 27 patients who received trifluridine/tipiracil, many had comorbidities of deep venous thrombosis or hemorrhage. The median overall survival was 12.4 months, and the median progression-free survival was 2.8 months. The median overall survival was 7.7 months in 19 patients without subsequent regorafenib. Grade 3 or higher toxicities were found in 51% of patients. No treatment discontinuation because of comorbidities was observed. CONCLUSION: Trifluridine/tipiracil can be safely administered while maintaining efficacy in patients who were ineligible for regorafenib.
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Adenocarcinoma/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Pirrolidinas/uso terapéutico , Timina/uso terapéutico , Trifluridina/uso terapéutico , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adulto , Anciano , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Comorbilidad , Combinación de Medicamentos , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Selección de Paciente , Compuestos de Fenilurea/uso terapéutico , Supervivencia sin Progresión , Piridinas/uso terapéutico , Pirrolidinas/efectos adversos , Estudios Retrospectivos , Terapia Recuperativa , Análisis de Supervivencia , Timina/efectos adversos , Resultado del Tratamiento , Trifluridina/efectos adversosRESUMEN
Background: The survival benefits of regorafenib (REG) and trifluridine/tipiracil hydrochloride (TFTD) have been demonstrated in chemorefractory patients with metastatic colorectal cancer (mCRC). However, the effects of crossover administration of REG and TFTD on patient survival remain unclear. The present study evaluated the association between exposure to REG and TFTD and overall survival (OS) in patients with mCRC using data from the REGOTAS study. Patients and Methods: We analyzed patients registered in the REGOTAS study, which retrospectively compared the efficacy and safety of use of REG or TFTD as later-line chemotherapy for chemorefractory mCRC patients. We compared the survival outcomes of cohort A (treated using both REG and TFTD) and cohort B (treated using either REG or TFTD). Results: A total of 550 patients (cohort A, n = 252; cohort B, n = 298) met the inclusion criteria. The median OS was significantly increased in cohort A compared with cohort B [9.6 months (95% confidence interval (CI), 8.9-10.9 months) vs. 5.2 months (95% CI, 4.4-6.0 months), P < 0.001]. Multivariate analysis revealed that cohort A was independently associated with a significant increase in OS [A vs. B: Hazard ratios (HR), 0.58; 95% CI, 0.47-0.72; P < 0.001]. Subgroup analysis adjusted using multivariate Cox model revealed a consistently better trend in most subgroups for cohort A compared with cohort B. Conclusions: Our study revealed prolonged survival in patients treated with REG and TFTD. Therefore, all active agents, including REG and TFTD, should be made available to mCRC patients.
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Regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) showed survival benefits in metastatic colorectal cancer patients previously treated with standard chemotherapies; therefore, we compared the efficacy and safety of these two treatments. Patients with metastatic colorectal cancer treated with REG or FTD/TPI as a salvage-line therapy from May 2014 to December 2017 were included. We retrospectively analyzed long-term survival, safety, and clinical outcomes. Among 134 patients, 57 and 77 received REG and FTD/TPI, respectively. The REG group received more prior systemic chemotherapies and significantly more frequent additional chemotherapies than the FTD/TPI group did. The median follow-up was 6.2 months, whereas the median overall survival was 9.9 and 11.4 months in the REG and FTD/TPI groups, respectively (hazard ratio = 0.954, p = 0.837). The median progression-free survival was 2.0 and 3.3 months in the REG and FTD/TPI groups, respectively (hazard ratio = 0.52, p = 0.00047), indicating significant differences, whereas the objective response and disease control rates did not differ. The median overall survival of patients with additional subsequent chemotherapies after disease progression was longer than that of patients without additional chemotherapy. The most frequent grade ≥3 adverse events were hypertension and neutropenia in the REG and FTD/TPI groups, respectively. Our study suggested that sequential use of both drugs may prolong survival.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales/tratamiento farmacológico , Compuestos de Fenilurea/uso terapéutico , Piridinas/uso terapéutico , Pirrolidinas/uso terapéutico , Trifluridina/uso terapéutico , Uracilo/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Combinación de Medicamentos , Resistencia a Antineoplásicos , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Terapia Recuperativa , Timina , Resultado del Tratamiento , Uracilo/uso terapéuticoRESUMEN
BACKGROUND: Although regorafenib or trifluridine/tipiracil (FTD/TPI) has been recognized as a later-line standard treatment in patients with metastatic colorectal cancer (mCRC), not all patients have beneficial outcomes. This study aimed to develop a prognostic scoring system for evaluating the overall survival (OS) benefit. METHODS: Patients included in the REGOTAS study, which comprised 489 patients (regorafenib group: 199; FTD/TPI group: 290 patients), were evaluated. OS was analyzed using multivariate Cox proportional model. The prognostic score was calculated using the worst four individual factors weighted by hazard ratio, and the total scores were categorized as low-, moderate-, and high-OS benefit. RESULTS: The worst four factors in the regorafenib group were AST > 40 IU/dL (point, + 3), CRP ≥ 1.0 mg/dL (+ 2), number of metastatic organ site ≥ 3 (+ 2), and duration from initiation of 1st-line chemotherapy < 18 months (+ 2), while they were AST (+ 2), CRP (+ 2), CA19-9 > 37.0 U/mL (+ 2), and ECOG PS ≥ 1 (+ 2) in the FTD/TPI group. These corresponded to a total prognostic score of > 5, 2-4, and 0 points in the regorafenib group and 8, 2-6, and 0 points in the FTD/TPI group. The median OS in the low, moderate, and high OS benefit group was 3.3 (95% CI 3.0-3.7), 8.1 (95% CI 6.4-9.7), and 12.6 months (95% CI 10.6-14.6) in the regorafenib group and 2.8 (95% CI 2.0-3.5), 7.5 (95% CI 6.6-8.3), and 15.4 months (95% CI 9.7-21.2) in the FTD/TPI group. CONCLUSION: These prognostic scores are useful for identifying patients with mCRC who will obtain survival benefits from these drugs.
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Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Compuestos de Fenilurea/uso terapéutico , Piridinas/uso terapéutico , Pirrolidinas/uso terapéutico , Trifluridina/uso terapéutico , Uracilo/análogos & derivados , Anciano , Neoplasias Colorrectales/patología , Combinación de Medicamentos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Timina , Resultado del Tratamiento , Uracilo/uso terapéuticoRESUMEN
We herein report the first case in which an escalated dose of sunitinib was effective, even after dose reduction. A 64-year-old man with gastrointestinal stromal tumor of the small intestine discontinued adjuvant imatinib because of interstitial pneumonia. After two years, peritoneal recurrence was detected. Sunitinib was started at 50 mg/day for 4 weeks every 6 weeks, after which the dosage was reduced to 37.5 mg/day because of grade 1 gastritis, stomatitis, and a fever. Four months later, computed tomography showed progressive disease. As the adverse events were well-controlled by medication, we escalated the dose to 50 mg/day and achieved a partial response.
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Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Sunitinib/uso terapéutico , Antineoplásicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Tumores del Estroma Gastrointestinal/patología , Humanos , Intestino Delgado/patología , Masculino , Persona de Mediana Edad , Sunitinib/administración & dosificación , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Alternate-day administration of S-1 is thought to reduce toxicities. This phase II study evaluated S-1 on alternate days combined with bevacizumab as first-line treatment for elderly patients with metastatic colorectal cancer. PATIENTS AND METHODS: Eligible patients had histologically proven colorectal adenocarcinoma, measurable metastatic lesions, age ≥ 75 years, Eastern Cooperative Oncology Group performance status ≤ 1, no previous chemotherapy, and refused oxaliplatin- or irinotecan-containing regimens. Patients received 40 mg, 50 mg, or 60 mg (body surface area ≤ 1.25 m2, > 1.25 to ≤ 1.50 m2, or > 1.50 m2, respectively) of S-1 twice orally on Sunday, Monday, Wednesday, and Friday every week. Bevacizumab (7.5 mg/kg) was administered every 3 weeks. The primary endpoint was progression-free survival. RESULTS: Of 54 enrolled patients, 50 patients were evaluated for efficacy and 53 for safety. The median age was 79 years (range 75-88 years). The median progression-free survival was 8.1 months (95% confidence interval (CI) 6.7-9.5 months). The median overall survival was 23.1 months (95% CI 17.4-28.8 months). The response rate was 44% (95% CI 30.2-57.8%), and the disease control rate was 88% (95% CI 79.0-97.0%). Grade 3 or higher hematologic, non-hematologic, and bevacizumab-related adverse events occurred in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Only 6 patients discontinued treatment due to adverse events. CONCLUSION: S-1 on alternate days combined with bevacizumab showed better tolerability and comparable survival compared with the results of similar studies.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adenocarcinoma/secundario , Anciano , Anciano de 80 o más Años , Bevacizumab/administración & dosificación , Neoplasias Colorrectales/patología , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Masculino , Metástasis de la Neoplasia , Ácido Oxónico , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , TegafurRESUMEN
INTRODUCTION: FOLFOXIRI plus bevacizumab has a promising efficacy as first-line systemic chemotherapy for metastatic colorectal cancer (mCRC). This study aimed to evaluate the safety and effectiveness of FOLFOXIRI plus antibodies. RESULTS: Fifty-five patients were enrolled (median age: 60 years, males: 25, females: 30). Twenty-six subjects had RAS mutations and 29 had RAS wild-type. Anti-VEGF and anti-EGFR antibodies were administered to 38 and 17 patients, respectively. The most common severe adverse event was neutropenia (51%). The overall response rate (ORR) was 69% (55% with anti-VEGF antibodies and 100% with anti-EGFR antibodies; P = 0.190), and the disease control rate was 98% (stable disease: 16 patients). With a median follow-up period of 18.4 months, the median progression-free survival (mPFS) was 11.0 months and the median overall survival (mOS) was 41.9 months. The mPFS and mOS did not significantly differ between patients treated with anti-EGFR antibodies and those with anti-VEGF antibodies. METHODS: We retrospectively collected data from mCRC patients treated with FOLFOXIRI plus antibodies between March 2014 and December 2017. CONCLUSIONS: FOLFOXIRI plus antibody therapy was effective in patients with mCRC. The response rate was higher in patients treated with anti-EGFR antibodies than in those treated with anti-VEGF antibodies.
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BACKGROUND: Reports of hepatitis B virus (HBV) reactivation in solid tumors are very limited, and their frequencies and risk factors were previously unknown. AIM: To evaluate the prevalence and risk factors of HBV reactivation in patients with solid tumors with resolved HBV infection. METHODS: All 1088 patients with solid tumors were assessed for eligibility; 251 patients had resolved HBV infection (negative for HBs antigen and positive for anti-HBc antibody and/or positive for anti-HBs antibody), and HBV-DNA was assessed for 243 of these patients in whom we analyzed the prevalence of HBV reactivation. Risk factors for HBV reactivation were exploratorily evaluated by analysis of a case-control study. RESULTS: The prevalence of HBV-DNA reactivation was 2.1% (95% confidence interval [CI], 0.3-3.9%). We did not observe any exacerbation of HBV-DNA by early intervention. A low anti-HBs antibody titer (<10.0 mIU/mL) and high average daily dexamethasone dose (>1.0 mg/day) were high risk factors, with odds ratios of 5.94 (95% CI, 1.15-30.6, P = 0.03) and 8.69 (95% CI, 1.27-58.8, P = 0.02), respectively. CONCLUSION: HBV reactivation in solid tumor patients was relatively rare. Therefore, risk factors that can identify targets for HBV screening must be determined in future studies.
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Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B/epidemiología , Hepatitis B/virología , Neoplasias/tratamiento farmacológico , Activación Viral/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Estudios de Casos y Controles , Femenino , Hepatitis B/tratamiento farmacológico , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Neoplasias/virología , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The main purposes of metastatic breast cancer (MBC) treatment are to prolong survival and maintain health-related quality of life (HRQOL). Compliance with the HRQOL assessment can be poor, particularly among patients who receive long-term treatment. One possible solution to overcoming this problem is to engage in real-time home monitoring by having patients report outcomes on their personal electronic devices. The objective of this study was to investigate compliance with HRQOL monitoring from home among MBC patients using the Computer-Based Health Evaluation System (CHES) to collect patient data. METHODS: Sixteen MBC patients who received outpatient chemotherapy or endocrine therapy, both with and without targeted therapy, were recruited. One eligibility criterion was the availability of a personal electronic device with access to the Internet. Patients were asked to enter HRQOL ratings from their personal electronic devices via CHES once every week for 12 weeks. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ C30) was used to evaluate HRQOL. The outcome examined was the questionnaire collection rate. RESULTS: Six patients (37.5%) were treated with chemotherapy only, one (6.2%) with endocrine therapy only, three (18.8%) with a combination of chemotherapy and targeted therapy, and six (37.5%) with a combination of endocrine and targeted therapy. Median questionnaire collection rate for the total of 12 weeks was 84.6% (interquartile range 44.3-100). The reasons for missing data were worsening of disease, forgetting, and device malfunction. CONCLUSIONS: Compliance with electronic HRQOL data collection in this cohort was acceptable, considering the general ideal collection rate of 70-80%. We are conducting a prospective study to determine whether the use of CHES to input electronic real-time feedback of HRQOL ratings improves patients' overall HRQOL.
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Neoplasias de la Mama , Computadores , Monitoreo Fisiológico/métodos , Calidad de Vida , Adulto , Anciano , Pueblo Asiatico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Monitoreo Fisiológico/instrumentación , Proyectos Piloto , Teléfono Inteligente , Encuestas y CuestionariosRESUMEN
Inflammatory myofibroblastic tumor (IMT), a rare sarcoma, is primarily treated via resection of the mass. However, in cases of recurrence or unresectable tumors, no standard care exists. While crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is only approved for non-small-cell lung cancer with ALK mutation, it is reportedly effective for other malignant tumors with ALK mutation. We herein report a case involving a 37-year-old woman with retroperitoneal IMT with ALK mutation, who experienced recurrence after complete resection, in whom crizotinib treatment resulted in complete response. ALK-inhibitor efficacy against malignancies with ALK mutations should be investigated in future.
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Quinasa de Linfoma Anaplásico/genética , Crizotinib/uso terapéutico , ADN de Neoplasias/genética , Mutación , Neoplasias Retroperitoneales/tratamiento farmacológico , Sarcoma/tratamiento farmacológico , Adulto , Quinasa de Linfoma Anaplásico/metabolismo , Análisis Mutacional de ADN , Femenino , Humanos , Imagen por Resonancia Magnética , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias Retroperitoneales/diagnóstico , Sarcoma/diagnóstico , Sarcoma/genéticaRESUMEN
Diffuse liver metastasis is a rare pattern of liver metastasis that is associated with hepatic failure and poor prognosis. We experienced 2 cases of acute liver failure due to diffuse metastasis that could not be detected using computed tomography. In case 1, it was difficult to differentiate diffuse metastasis from alcoholic hepatitis. In case 2, it was difficult to diagnose diffuse liver metastasis because the patient had no history of malignancy. When liver enzyme levels are elevated, it is necessary to consider liver metastasis as a potential cause, regardless of computed tomography findings.
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INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) is effective as a predictive factor for lung cancer treated with nivolumab. The objective of this study was to determine the effectiveness of NLR for patients with advanced gastric cancer (AGC) treated with nivolumab. METHODS: This was a multicenter, retrospective study of patients with AGC treated with nivolumab from June 2017 to December 2017. The NLRs were calculated before the first cycle (NLRpre) and two weeks after the first administration (NLRpost). RESULTS: Twenty-six patients were enrolled (males 19, females 7) with a median age of 64 years. The overall response rate was 15%. The median PFS was 80 days (range, 11 - 265) and the median OS was 290 days (range, 21 - 332). Stratified with high NLR (≥5) and low NLR (<5), the median PFS was shorter in the high NLRpre arm (87 vs. 45 days; p=0.066) and significantly shorter in the high NLRpost arm (94 vs. 28 days; p=0.014). The median OS was significantly shorter in the high NLRpre arm (290 vs. 175 days; p=0.008) and in the high NLRpost arm (290 vs. 69 days; p<0.001). CONCLUSION: NLR may be an effective prognostic factor in patients with AGC treated with nivolumab.
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PURPOSE: Optimal salvage chemotherapy for patients with treated advanced/metastatic gastric cancer (AGC) is unknown. Irinotecan is commonly used in Japan. Ramucirumab, a human IgG-1 monoclonal antibody targeting the extracellular domain of VEGF receptor 2, is the first molecularly targeted agent proven to be effective in second-line therapy for AGC in combination with chemotherapy. We sought to determine the maximum tolerated dose (MTD) and recommended dose (RD) of ramucirumab plus irinotecan for AGC previously treated with fluoropyrimidine with/without platinum and taxane. METHODS: Patients received systemic chemotherapy with ramucirumab (8 mg/kg) and irinotecan on day 1, repeated every 2 weeks. A decrease in irinotecan dose was planned from start level 1 (irinotecan 150 mg/m2). This trial was registered with the University Hospital Medical Network (UMIN no. 000018606). RESULTS: Six patients were enrolled from August 2015 to September 2017. No dose-limiting toxicity (DLT) was observed, and the maximum tolerated dose (MTD) was not reached at level 1. Irinotecan 150 mg/m2 in combination with ramucirumab 8 mg/kg was administered with acceptable toxicity, and all patients were treated at these doses. No treatment-related deaths were observed. Adverse events of Grade 3/4 were neutropenia (17%), anemia (17%) and hypertension (17%). Patients were evaluated using the RECIST criteria, and response rate and disease control rate were 17% and 83%, respectively. CONCLUSIONS: Salvage chemotherapy with irinotecan plus ramucirumab was well-tolerated by patients previously treated for AGC. RD was defined as irinotecan 150 mg/m2 in combination with ramucirumab 8 mg/kg.
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Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Irinotecán/administración & dosificación , Terapia Recuperativa/métodos , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Esquema de Medicación , Femenino , Humanos , Irinotecán/efectos adversos , Estimación de Kaplan-Meier , Masculino , Dosis Máxima Tolerada , Platino (Metal)/administración & dosificación , Platino (Metal)/uso terapéutico , Análisis de Supervivencia , Taxoides/administración & dosificación , Taxoides/uso terapéutico , RamucirumabRESUMEN
Following the ATTRACTION-2 study, nivolumab was approved for advanced gastric cancer in Japan. However, pseudoprogression and hyperprogressive disease have been reported in patients treated with immune checkpoint inhibitors. We report a patient with gastric cancer who received nivolumab after radiotherapy only to experience rapid progression within the irradiation field after the first immunotherapy session. A 66-year-old man with dysphagia visited our hospital and was diagnosed with stage IV gastroesophageal cancer (human epidermal growth factor receptor-2 score = 0). He commenced a G-SOX regimen (S-1 80 mg/m2 on days 1-14 and oxaliplatin 100 mg/m2 on day 1, repeated every 3 weeks) in June 2017. The dysphagia worsened despite 3 cycles of G-SOX, and computed tomography (CT) revealed constriction of the gastroesophageal junction. To ameliorate the dysphagia, palliative chemoradiotherapy (S-1 and 50.4 Gy in 28 fractions) was performed starting in August 2017. The patient's dysphagia had not resolved after completing radiotherapy, and pain on swallowing worsened. Nivolumab (3 mg/m2 every 2 weeks) was administered 7 days after the completion of radiotherapy. The patient experienced malaise and worsening dysphagia before the second cycle. CT 15 days after the first nivolumab administration revealed rapid progression in the irradiation field. His general condition rapidly deteriorated, and he died 24 days after the first administration. This episode suggests that administration of nivolumab after radiotherapy may be a risk factor for hyperprogressive disease.
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BACKGROUND: FOLFOXIRI is now regarded as the chemotherapy regimen that offers the best platform for the treatment of colorectal cancer. However, the safety and efficacy of FOLFOXIRI + panitumumab has not been demonstrated. We conducted a phase I study to determine the recommended dose of FOLFOXIRI + panitumumab as first-line treatment for RAS wild-type metastatic colorectal cancer (mCRC). METHODS: Patients received combination therapy consisting of panitumumab (6 mg/kg on day 1) + FOLFOXIRI [irinotecan (CPT-11), oxaliplatin (L-OHP) 85 mg/m2, and folinate (LV) 200 mg/m2] on day 1, followed by fluorouracil (5-FU) 3200 mg/m2 infused as a 46-h continuous infusion starting on day 1) repeated every 2 weeks as first-line treatment of RAS wild-type mCRC patients. A decrease in CPT-11 dose was planned (started at level 1: CPT-11 165 mg/m2). RESULTS: Seven patients were enrolled, and six were assessed for safety and efficacy. Maximum tolerated dose was not reached at level 1; all patients were treated at these levels. The common Grade 3 or 4 relevant toxicities were diarrhea (50%), hypokalemia (33%) and stomatitis (33%). No treatment-related deaths occurred. Of the six patients assessed four had partial response and the two others had stable disease; hence, the response rate was 66.7% (95% confidence interval 28.9-100%) and the disease control rate was 100%. Time to protocol treatment failure was 7.2 (1.4-7.3) months. CONCLUSION: The FOLFOXIRI + panitumumab chemotherapy regimen was well tolerated by our patients with mCRC and showed promising anti-tumor activity. The recommended phase II dose was determined to be the same as the standard doses of this regimen used worldwide.