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PURPOSE: Pain is one of the most common and devastating symptoms in cancer patients, and misunderstandings on the patient's part can cause major obstacles in pain management. METHOD: We evaluated factors associated with patient's high barrier score to managing cancer-associated pain by having 201 patients complete the Korean Barriers Questionnaire II, the Brief Pain Inventory--Korean, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Korean Beck Depression Inventory. The Pain Management Index (PMI) was also assessed. RESULTS: The patients were from nine oncology clinics in university hospitals and a veterans' hospital in South Korea. The median pain score (0-10 scale) was 4, with a median percentage of pain improvement during the last 24 h of 70 %. A total of 150 patients (75 %) received strong opioids, and 177 (88 %) achieved adequate analgesia (positive PMI). Mean scores ± SD for the Barriers Questionnaire II ranged from 1.5 ± 1 to 2.8 ± 1.1, with the harmful effects subscale the highest. In the multiple regression model, depression was significantly associated with total barrier score to pain management (p < 0.0001). Pain reduction was significantly associated with the fatalism subscale. CONCLUSIONS: Depression was associated with high barrier score in patients with cancer pain. Management of cancer pain should include screening for depression, and management of depression could reduce patient-reported barriers to pain management.
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Neoplasias/complicações , Manejo da Dor , Dor/tratamento farmacológico , Dor/psicologia , Intervalos de Confiança , Estudos Transversais , Depressão , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/fisiopatologia , Dor/etiologia , Manejo da Dor/psicologia , Satisfação do Paciente , Qualidade de Vida , República da Coreia , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Genetic differences may be associated with the response to tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML). In this study, we identified genetic alterations between rapid and slow responders (BCR/ABL1 International Scale at 6 months: ≤0.1 % vs. > 0.1 %) of TKI treatment in chronic phase CML patients. Our analyses involved single nucleotide polymorphism (SNP), a Genome Wide Association Study and a Network-wide Association Study (NetWAS). Seventy-two patients from 16 institutions were enrolled and treated with a TKI, nilotinib. Gene Set Analysis identified genetic alterations in pathways related to the differentiation, proliferation, and activity of various innate immune cells. The NetWAS analysis found that genes associated with natural killer (NK) cells (PTPRCAP, BLNK, HCK, ARHGEF11, GPR183, TRPV2, SHKBP1, CD2) showed significant differences between rapid and slow responders of nilotinib. However, we found no significantly different genetic alterations according to the response in the SNP analysis. In conclusion, we found that rapidity of response to TKI was associated with pathway-associated genetic alterations in immune cells, particularly with respect to NK cell activity. These results suggested that the innate immune system at initial diagnosis had an important role in treatment response in patients with CML.
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Estudo de Associação Genômica Ampla , Leucemia Mielogênica Crônica BCR-ABL Positiva , Proteínas de Fusão bcr-abl/genética , Humanos , Células Matadoras Naturais/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Ultra-deep sequencing detects low-frequency genetic mutations with high sensitivity. We used this approach to prospectively examine mutations in the BCR/ABL1 tyrosine kinase from patients with newly diagnosed, chronic-phase chronic myeloid leukemia (CML) treated with the tyrosine kinase inhibitor nilotinib. Between May 2013 and November 2014, 50 patients from 18 institutions were enrolled in the study. We screened 103 somatic mutations and found that mutations in the P-loop domain were the most frequent (173/454 mutations in the P-loop) and noted the presence of the V299 L mutation (dasatinib-resistant/nilotinib-sensitive) in 98 % of patients (49/50). No patients had Y253H, E255 V, or F359 V/C/I mutations, which would recommend dasatinib rather than nilotinib treatment. The S417Y mutation was associated with lower achievement of a major molecular response (MMR) at 6 months, and the V371A mutation was associated with reduced MMR and MR4.5 durations (MMR for 2 years: 100 % for no mutation vs. 75 % for mutation, P=0.039; MR4.5 for 15 months: 94.1 % vs. 25 %, P=0.002). Patients with known nilotinib-resistant mutations had lower rates of MR4.5 achievement. In conclusion, ultra-deep sequencing is a sensitive method for genetic-based treatment decisions. Based on the results of these mutational analyses, nilotinib treatment is a promising option for Korean patients with CML.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Mutação , Dasatinibe/administração & dosagem , Feminino , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Pirimidinas/administração & dosagem , Taxa de SobrevidaRESUMO
Gefitinib, a selective inhibitor of epidermal growth factor receptor tyrosine kinase is an effective agent used in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Adverse drug reactions were frequently observed in the skin, gastrointestinal tract, and liver, but they were generally mild in severity and reversible. Therefore, gefitinib has been regarded as a relatively safe agent. As a serious adverse effect, however, acute lung injury has been reported. The present report describes a patient with NSCLC who developed bilateral subdural hemorrhage as a possible adverse drug reaction after gefitinib therapy. We expect that this case may provide a reference for clinicians being involved in the treatment with gefitinib.
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Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Hematoma Subdural/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/efeitos adversos , Idoso , Feminino , Gefitinibe , Hematoma Subdural/tratamento farmacológico , Humanos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Brain metastases (BMs) are found in about 10% of patients with newly diagnosed non-small cell lung cancer (NSCLC). This retrospective study was conducted to assess the clinical outcomes and prognostic factors of patients who received chemotherapy after cranial irradiation for NSCLC with synchronous BMs. MATERIALS AND METHODS: From January 2000 through July 2007, we reviewed the medical records of patients who received systemic chemotherapy following cranial irradiation for BMs from newly diagnosed NSCLC. RESULTS: A total of 40 patients were included in this review. As the first-line chemotherapy, a total of 114 cycles were administered, for a median number of 2 cycles per patient (range, 0.5-8 cycles). Thirty-four patients (85%) received platinum-based combination regimen and the remaining 6 received chemotherapy with a single agent. Sixteen (40%) patients, 11 of whom had ECOG of 2, only received 1 cycle or less of chemotherapy due to early death, rapid progression, clinical impairment, or toxicity. For 28 patients who were evaluable for response, the extracranial overall response rate was 43%. The median overall survival for all patients was 7 months (range, 0.9-25.3 months) and an estimated 1-year survival rate was 23%. Multivariate analysis revealed that ECOG status (P=0.018) and number of BM (P=0.038) were independent prognostic factors. CONCLUSION: Our results suggest that chemotherapy can be used to increase survival of patients treated with cranial irradiation for newly diagnosed NSCLC with synchronous BM. However, systemic chemotherapy should be carefully considered according to the patient's prognostic condition. Especially, patients with good performance status and limited number of BM may be good candidates for systemic chemotherapy after cranial irradiation.
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Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/secundário , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Advanced or metastatic gastric cancer, which is one of the most common malignancies in Korea, is difficult to cure by surgery alone and generally requires combination chemotherapy. Paclitaxel is active against gastric cancer and when combined with 5-fluorouracil/leucovorin and/or cisplatin is effective in the treatment of gastric cancer. We attempted to determine the effect and safety with the combination of paclitaxel with split cisplatin and 5-fluorouracil/leucovorin in advanced or metastatic gastric cancer. Patients with histologically-proven locally advanced/metastatic or recurrent gastric cancer with an ECOG performance status 0-2 were enrolled. The patients received 135 mg/m(2) of paclitaxel as a 3-h intravenous infusion on day 1 and 5-fluorouracil (1200 mg/m(2)) plus leucovorin (20 mg/m(2)) as an intravenous infusion over 12 h plus cisplatin (30 mg/m(2)) by continuous intravenous infusion on days 1-3, every 21 days. Between September 2003 and April 2005, 30 patients (26 evaluable patients) with a median age of 57 years (range 34-74) were enrolled and underwent 111 completed treatment cycles (a median of 3 cycles per patient). Of the evaluable patients, 12 patients showed a partial response and 8 patients had stable disease. The overall response rate was 46.2%. The median progression-free survival was 5.6 months (95% CI. 3.76-7.4 months), and the median overall survival was 9.6 months (95% CI. 6.67-12.47 months). The hematologic and non-hematologic toxicities were tolerable. The grade III and IV hematologic toxicities were anemia (6.8%) and neutropenia (2.6%). Febrile neutropenia was observed in 1 patients and 1 cycle. Other hematologic toxicities and grade III and IV non-hematologic toxicities, except nausea (66.7%) and vomiting (33.3%) were uncommon and not severe. TPFL combination chemotherapy is effective and tolerable with acceptable toxicities in patients with advanced/metastatic, recurrent gastric cancer.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Terapia de Salvação/métodos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AEs) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML-CP). We investigated the 2-year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations (PNCs). In this open-label, multi-institutional phase 4 study, 110 Philadelphia chromosome-positive CML-CP patients were treated with nilotinib at a starting dose of 300 mg twice daily. Molecular responses (MRs) and AEs were monitored for up to 24 months. The 24-month cumulative MR4.5 rate was evaluated as the primary endpoint. Plasma samples were collected from 94 patients to determine PNCs, and the per-patient mean was used to categorize them into four mean PNC (MPNC) groups. Cumulative MR rates and safety were compared between groups. With a median follow-up of 22.2 months, the 24-month cumulative MR4.5 rate was 56.2% (95% confidence interval, 44.0%-8.3%), and the median time to MR4.5 was 23.3 months. There were no significant differences in the cumulative rates of major molecular response, MR4 , and MR4.5 between MPNC groups. One patient died due to acute viral hepatitis, and two developed hematological or cytogenetic relapse, while no progression to accelerated or blast phase was observed. Safety results were consistent with previous studies with no new safety signal identified. Across the MPNC groups, there was no significant linear trend in the frequency of AEs. Nilotinib is highly effective for the treatment of CML-CP with manageable AEs. The measurement of PNC has no predictive value for patient outcomes and is thus not found to be clinically useful. This study is registered with clinicaltrials.gov, Number NCT03332511.
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Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pirimidinas/administração & dosagem , Pirimidinas/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , República da Coreia , Espectrometria de Massas em Tandem , Resultado do TratamentoRESUMO
BACKGROUND: The combination of gemcitabine and cisplatin is among the most active regimens for the treatment of NSCLC. However, the optimal dose and schedule for administration of the two drugs has not yet been determined. We investigated the activity and toxicity of a gemcitabine and split-dose cisplatin regimen in an outpatient setting for patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From June 2004 to May 2005 patients with stage IIIB or IV who had not had prior chemotherapy entered the study. Treatment consisted of gemcitabine 1250 mg/m2 and cisplatin 35 mg/m2, both given intravenously on days 1 and 8 every 21 days. RESULTS: Forty-five patients were entered this study. Patient characteristics were as follows: male/female, 34/11; median age (range), 62 (30-76) years; ECOG PS 0/1/2, 7/30/8; stage IIIB/IV, 18/27. A total of 168 cycles were delivered, with a median of 4 cycles (range, 1-6). All patients were evaluable for toxicity. Grade 3 and 4 toxicities according to the NCI toxicity criteria included neutropenia in 8 patients (18%), anemia in 4 (9%), thrombocytopenia in 7 (15%), and emesis in 1 (2%). Of 42 patients assessable for response, 23 patients showed a partial remission. On intent-to-treat basis, the overall response rate was 51% (95% CI, 37-65%). Median time to progression was 6.0 months (range, 1.2-12.0 months) and median overall survival was 13.1 months (range, 1.4-17 months). CONCLUSIONS: This regimen with gemcitabine and split-dose cisplatin using a 21-day schedule appears to be active and very well-tolerated in an outpatients setting for patients with advanced NSCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
PURPOSE: This study was conducted to evaluate the efficacy and safety of the combination of capecitabine and oral leucovorin (LV) as a third-line chemotherapy for patients with metastatic colorectal cancer (CRC) showing resistance to irinotecan- and oxaliplatin-containing regimens. METHOD: Patients who showed disease progression while receiving or within 6 months of discontinuing irinotecan- and oxaliplatin-containing regimens received capecitabine 825 mg/m(2) in combination with oral LV at a fixed dose of 30 mg, twice a day for 2 weeks followed by a 1-week rest. RESULTS: Twenty-five patients were enrolled from July 2011 to June 2014. Three patients achieved PR, and 11 showed SD. The overall response rate was 12 %, and disease control rate was 56 %. With a median follow-up of 6.8 months, the median time to progression was 2.8 months and the median overall survival was 7.1 months. The most common non-hematologic toxicity was hand-foot syndrome (40 %), followed by mucositis (28 %) and diarrhea (12 %). Grade 3 hand-foot syndrome occurred in two patients (8 %), and grade 3 mucositis in one. Hematologic toxicities were mild, and only one patient developed grade 3 thrombocytopenia. CONCLUSION: The combination of capecitabine and oral LV showed a modest activity and tolerable toxicity profile in metastatic CRC patients pretreated with irinotecan- and oxaliplatin-containing regimens. Oral LV seems to be able to reduce the usual dose of capecitabine when the two drugs are combined.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina , Neoplasias Colorretais/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Seguimentos , Humanos , Irinotecano , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Bone marrow biopsy is a standard method for the evaluation of bone marrow infiltration by lymphoma; however, it is an invasive and painful procedure. Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is a noninvasive imaging technique with the potential to detect bone marrow involvement by lymphoma. MATERIALS AND METHODS: We retrospectively reviewed medical records of lymphoma patients. All patients were examined by FDG PET-CT and iliac crest bone marrow biopsy for initial staging work-up. RESULTS: The study population comprised 94 patients (median age, 60 years; 56 males) with Hodgkin's lymphoma (n=8) or non-Hodgkin's lymphoma (n=86). Maximum standardized uptake values on the iliac crest of patients with lymphoma infiltrated bone marrow were significantly higher than those of patients with intact bone marrow (2.2±1.2 g/mL vs. 1.3±0.4 g/mL; p=0.001). The calculated values for FDG PET-CT during evaluation of bone marrow involvement were as follows: sensitivity 50%, specificity 96%, positive predictive value 80%, negative predictive value 85%, and positive likelihood ratio (LR+) 11.7. The value of LR+ was 16.0 in patients with aggressive subtypes of non-Hodgkin's lymphoma (NHL). CONCLUSION: FDG PET-CT could not replace bone marrow biopsy due to the low sensitivity of FDG PET-CT for detection of bone marrow infiltration in lymphoma patients. Conversely, FDG PET-CT had high specificity and LR+; therefore, it could be a useful tool for image-guided biopsy for lymphoma staging, especially for aggressive subtypes of NHL. In addition, unilateral bone marrow biopsy could be substituted for bilateral bone marrow biopsy in lymphoma patients with increased FDG uptake on any iliac crest.
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BACKGROUND: Capecitabine plus oxaliplatin (XELOX) is considered one of the primary chemotherapy regimens for patients with metastatic colorectal cancer (CRC). Oxaliplatin plus S-1 (OS) has also demonstrated significant efficacy in CRC. We performed this randomized phase II study to evaluate the efficacy and toxicity of XELOX versus OS as first-line chemotherapy in patients with metastatic CRC. METHODS: Patients were assigned randomly to receive either OS or XELOX chemotherapy. Oxaliplatin was administered intravenously to all patients at a dose of 130 mg/m(2) on day 1. Patients received either S-1 (40 mg/m(2)) or capecitabine (1,000 mg/m(2)), twice a day for 2 weeks, followed by a 1-week rest. RESULTS: Forty-two patients were assigned to the OS arm and 44 to the XELOX arm. The overall response rate was 33.3% (95% CI, 18.8-47.2) in the OS arm and 40.9% (95% CI, 25.5-54.4) in the XELOX arm (P = 0.230). The disease control rate was significantly higher in the OS arm than the XELOX arm [92.9% (95% CI, 83.7-100) versus 77.3% (95% CI, 64.5-89.4), P = 0.044]. With a median follow up of 17.9 months, the median progression-free survival was 6.1 months in the OS arm and 7.4 months in the XELOX arm, respectively (P = 0. 599). The median survival time was 18.7 months in the OS arm and 20.1 months in the XELOX arm (P = 0.340). The most common grade 3/4 hematologic toxicity was thrombocytopenia in both arms (19.0% for OS and 28.6% for XELOX). Grade 3/4 neutropenia was observed more frequently in the XELOX arm than the OS arm (16.7% vs. 2.4%, P = 0.026). CONCLUSION: Both OS and XELOX were effective and well tolerated in patients with metastatic CRC. Our results indicate that the combination of oxaliplatin and S-1 is a possible additional therapeutic strategy for such patients.
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This study was conducted to investigate the efficacy of the induction chemotherapy followed by radiotherapy in anal cancer. Twenty-three patients diagnosed with anal cancer between March 1991 and February 1999 were treated with induction chemotherapy with 5-fluorouracil based regimens followed by external beam radiation. After a median follow-up of 78 months, the overall survival and the disease-free survival at 5 years was 71.3 and 67.5%, respectively. The colostomy-free survival at 5 years was 91%, as the inguinal lymph nodes were the most frequent site of relapse. Serious side effects did not occur and late complications did not develop either. Induction chemotherapy followed by radiotherapy in patients with anal cancer is effective in terms of its response and preserving the anal sphincter without serious acute and late complications.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Adulto , Idoso , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Estudos de Coortes , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Estadiamento de Neoplasias , Indução de Remissão , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: Combination therapy with aprepitant, serotonin receptor antagonist, and steroids improves the complete response rate of both acute and delayed chemotherapy-induced nausea and vomiting (CINV). However, it is not known whether ramosetron is suitable for administration in combination with aprepitant. Therefore, we conducted a multicenter, open-label, prospective, phase II study in order to assess the efficacy and tolerability of combination therapy with ramosetron, aprepitant, and dexamethasone (RAD) for prevention of cisplatin-based CINV in chemotherapy-naïve patients with solid cancers. MATERIALS AND METHODS: Forty-one patients with various solid cancers (31 male and 10 female; median age, 59 years) who received treatment with highly emetogenic chemotherapy (median cisplatin dose, 70 mg/m(2); range 50 to 75 mg/m(2)) were enrolled in this study. Oral aprepitant (125 mg on day 1; 80 mg on days 2 and 3), intravenous ramosetron (0.6 mg on day 1), and oral dexamethasone (12 mg on day 1; 8 mg on days 2-4) were administered for prevention of CINV. RESULTS: The complete response (no emesisand retching and no rescue medication) rate was 94.9% in the acute period (24 hours post-chemotherapy), 92.3% in the delayed period (24-120 hours post-chemotherapy), and 92.3% in the overall period (0-120 hours). The absolute complete response (complete response plus no nausea) rate was 74.4% in the acute period, 51.3% in the delayed period, and 46.2% in the overall period. There were no grade 3 or 4 toxicities related to these antiemetic combinations. CONCLUSION: RAD regimen is a safe and effective antiemetic treatment for prevention of CINV in patients receiving highly emetogenic chemotherapy.
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This study was conducted to evaluate the efficacy and safety of the combination of mitomycin-C (MMC) and S-1 as third-line chemotherapy for patients with advanced colorectal cancer (CRC) showing resistance to irinotecan- and oxaliplatin-containing regimens. Patients were recruited into the study from January 2009 and 10 patients were enrolled for 10 months. However, since no patients had shown a response by 10 months, the study was terminated early according to the protocol. MMC 7 mg/m(2) was administered intravenously on day 1 every 6 weeks in the first 4 cycles. S-1 was administered twice daily at 35 mg/m(2), within 1 h of meals on days 1-14. Following a rest for 7 days, S-1 was administered again on days 22-35, followed by a 7-day rest. A total of 14 cycles were delivered for 10 patients. All 10 patients were assessable for response. A total of 3 patients (30%) had stable disease and the remaining 7 showed disease progression. With a median follow-up of 7 months, the median overall survival was 10.5 months. Grade 3-4 myelotoxicities included neutropenia in two patients, anemia in two and thrombocytopenia in one. Grade 1-2 nausea and vomiting developed in 5 patients. One patient experienced grade 3 diarrhea. Grade 1-2 hand-foot syndrome occurred in 4 patients. In conclusion, the combination of MMC and S-1 as third-line chemotherapy in patients with advanced CRC appears to be well tolerated but has poor activity.
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BACKGROUND: Docetaxel and cisplatin combination chemotherapy is established first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). We evaluated a weekly schedule of docetaxel and cisplatin for efficacy and tolerability in patients with chemotherapy-naive NSCLC. METHODS: Patients enrolled in this study had stage IIIB or IV NSCLC with measurable disease, no prior chemotherapy, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. Treatment consisted of docetaxel 40 mg/m(2) and cisplatin 35 mg/m(2) given on D1 and D8 every 3 weeks. Patients were evaluated for response after every 2 cycles of treatment. RESULTS: Thirty six patients were enrolled, and 35 underwent treatment. Of these, 29 were males and 7 females, median age was 61 years (range, 38-68). About 31 patients had ECOG PS 0-1 and 4 patients had ECOG PS 2. Fifty seven percentage (20/35) of patients had adenocarcinoma and 74.3% (26/35) had stage IV disease. A total of 153 cycles of chemotherapy were administered. Of the 35 patients treated, 17 (48.6%) achieved partial response, 11 (31.4%) showed stable disease, and 6 (17.1%) had progressive disease. Median duration of response was 5.3 months (95% CI: 4.2-6.2 months), and median time to disease progression was 4.6 months (95% CI: 2.9-6.3 months). Estimated overall survival at 1 year was 65.7%. The major hematologic toxicity was myelosuppression. Grade 3 or 4 anemia occurred in 6 cycles, and grade 3 or 4 neutropenia was observed in four cycles. Major non-hematologic toxicities were grade 3 nausea in three patients and grade 3 fatigue in two patients. Three patients developed pneumonia and one patient had infectious colitis. There were no treatment-related deaths in this study. CONCLUSIONS: Weekly schedule of docetaxel and cisplatin as first-line treatment for NSCLC had good efficacy and manageable toxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Progressão da Doença , Docetaxel , Esquema de Medicação , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Sobrevida , Taxoides/administração & dosagem , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Although platinum-based doublet chemotherapy is considered as standard of care for patients with advanced non-small cell lung cancer (NSCLC), most of them are eventually supposed to experience disease progression. Pemetrexed, docetaxel, erlotinib, and gefitinib have been shown to be active as monotherapy for pretreated patients. In this study, the efficacy of pemetrexed and carboplatin as a salvage therapy for patients with advanced NSCLC is evaluated. PATIENTS AND METHODS: From March 2007 to February 2009, 32 patients who were diagnosed with inoperable NSCLC and treated with one or more prior cisplatin-based chemotherapies were enrolled. Treatment consisted of pemetrexed 500 mg/m(2) over a 10-min intravenous infusion and carboplatin at an AUC 5 mg/mL/min over a 30-min intravenous infusion on Day 1 of a 21-day cycle. All patients were supplemented with folic acid and vitamin B12 to reduce the hematological toxicity of pemetrexed. RESULTS: There were one (3.1%) complete response and five partial (15.6%) responses. The overall response rate was 18.8% and the median response duration was 4.4 months. Among the responders, four patients had adenocarcinoma and two had squamous cell carcinoma. Nine patients had stable disease, and the disease control rate was 46.9%. With a median follow up duration of 9.4 months, the median time to progression was 2.3 months and the median OS was 9.4 months. Seven patients (21.9%) experienced grade 3 and 4 hematologic toxicities; one anemia (3.1%), six neutropenia (18.8%), and six thrombocytopenia (18.8%). Two patients experienced grade 4 febrile neutropenia with infection. Four patients (12.5%) experienced grade 3 non-hematologic toxicities; four asthenia (12.5%), two anorexia (6.3%), and one stomatitis (3.1%). Grade 1-2 peripheral neuropathy developed in 13 patients (40.6%). CONCLUSION: The combination of pemetrexed and carboplatin showed favorable toxicity profiles and activity in the pretreated patients with advanced NSCLC. It is suggested that this regimen can be a good chemotherapeutic option as a salvage therapy for patients with NSCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Feminino , Glutamatos/administração & dosagem , Glutamatos/efeitos adversos , Guanina/administração & dosagem , Guanina/efeitos adversos , Guanina/análogos & derivados , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Pemetrexede , Terapia de Salvação , Taxa de SobrevidaRESUMO
PURPOSE: To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy on metastatic gastric cancer. PATIENTS AND METHODS: Docetaxel and oxaliplatin were administered intravenously on day 1 and S-1 was administered orally on days 1-14 of every 21-day cycle. The doses of docetaxel/oxaliplatin/S-1 in the phase I study were level -1A, 52.5/80/60 mg/m(2); level -1B, 52.5/80/80 mg/m(2); level 1A, 52.5/105/80 mg/m(2); level 1B, 52.5/130/80 mg/m(2); level 2A, 60/105/80 mg/m(2); level 2B, 60/130/80 mg/m(2); level 3A, 67.5/105/80 mg/m(2); level 3B, 67.5/130/80 mg/m(2); level 4A, 75/105/80 mg/m(2); level 4B, 75/130/80 mg/m(2). RESULTS: Nine patients were enrolled. One of six patients at level 1A and two of three patients at level 1B developed dose-limiting toxicity (febrile neutropenia) during the initial two cycles. Therefore, the doses used at levels 1B and 1A were defined as the MTD and RD, respectively. All patients were evaluated for toxicity and response. Six partial responses were noted, and the overall response rate was 67%. CONCLUSION: The RD of the DOS regimen in patients with advanced gastric cancer was docetaxel 52.5 mg/m(2) and oxaliplatin 105 mg/m(2) on day 1 and S-1 80 mg/m(2) on days 1-14 of every 21-day cycle. A phase II study using the RD is currently underway.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Gastrectomia , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/patologia , Taxoides/administração & dosagem , Tegafur/administração & dosagemRESUMO
PURPOSE: To determine the dose-limiting toxicity (DLT) and activity of combination with docetaxel and S-1 on unresectable gastric cancer. PATIENTS AND METHODS: Docetaxel was administered intravenously on day 1 and S-1 was administered orally on days 1-14, every 3 weeks. Doses of each drug in phase I study were docetaxel 60-75 mg/m(2) and S-1 60-80 mg/m(2). A phase II study was conducted with the recommended dose (RD) based on phase I. RESULTS: Sixty-five patients (median age 54 years) were enrolled. The DLTs were neutropenia with fever or stomatitis. The RD was docetaxel 75 mg/m(2) and S-1 60 mg/m(2). Two patients (aged 66 and 64 years) developed septic shock during the initial part of phase II study. A phase I study at lower dose (docetaxel 60 mg/m(2) and S-1 80 mg/m(2)) was conducted for patients older than 60 years, and this dose was determined as the RD for these patients. In the phase II study, frequent grade 3/4 toxicities were neutropenia (47%) and febrile neutropenia (26%). The overall response rate was 50% (95% CI, 35-66%) and median survival was 15.3 months (95% CI, 10.0-20.6 months). CONCLUSIONS: Combination with docetaxel and S-1 was active against advanced gastric cancer and gave manageable toxicities.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel , Combinação de Medicamentos , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Recidiva , Neoplasias Gástricas/patologia , Taxoides/administração & dosagem , Tegafur/administração & dosagemRESUMO
We investigated early postoperative morbidity, mortality, and long-term outcomes in patients with liver cirrhosis (LC) who had undergone curative surgery for gastric cancer. The medical records of patients with LC who had undergone radical gastrectomy for gastric adenocarcinoma between January 1996 and September 2006 were retrospectively reviewed. A total of 57 patients were enrolled in this study. Forty-six patients (81%) were classified into Child's class A. In 22 patients (39%) postoperative complications developed, the most common being ascites (23%), followed by wound infection and hepatic encephalopathy. Postoperative ascites occurred more frequently in patients with Child's class B or C than in those with class A (63.6% vs 13%, P = 0.001). Massive ascites developed in 4 patients, 3 of whom had Child's class B and underwent D2 lymph node (LN) dissection, and 1 of whom had Child's class C and a D1 LN dissection. Postoperative mortality occurred in 5 patients (9%), with a significantly higher mortality rate for patients with Child's class B or C than for those with class A (27.2% vs 4.3%, P = 0.045). With a median follow-up of 32 months, the estimated 5-year survival rate for all patients was 54%. Regardless of the tumor depth, overall survival was longer for patients with Child's class A than for those with Child's class B or C. These results demonstrated that radical gastrectomy with extended LN dissection is feasible in patients with compensated LC. For patients with moderate to severe hepatic dysfunction, however, D1 or less extensive LN dissection may be the more reasonable surgical procedure.
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Adenocarcinoma/cirurgia , Cirrose Hepática/epidemiologia , Neoplasias Gástricas/cirurgia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Idoso , Comorbidade , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/mortalidade , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
Autoimmune hemolytic anemia associated with an ovarian teratoma is a very rare disease. However, treating teratoma is the only method to cure the hemolytic anemia, so it is necessary to include ovarian teratoma in the differential diagnosis of autoimmune hemolytic anemia. We report herein on a case of a young adult patient who had severe autoimmune hemolytic anemia that was induced by an ovarian teratoma. A 25-yr-old woman complained of general weakness and dizziness for 1 week. The hemoglobin level was 4.2 g/dL, and the direct and indirect antiglobulin tests were all positive. The abdominal computed tomography scan revealed a huge left ovarian mass, and this indicated a teratoma. She was refractory to corticosteroid therapy; however, after surgical resection of the ovarian mass, the hemoglobin level and the reticulocyte count were gradually normalized. The mass was well encapsulated and contained hair and teeth. She was diagnosed as having autoimmune hemolytic anemia associated with an ovarian teratoma. To the best of our knowledge, this is the first such a case to be reported in Korea.