RESUMO
Fragility fractures associated with glucocorticoid-induced osteoporosis (GIO) can markedly impair quality of life. However, only 20% of patients are treated in compliance with the relevant management guidelines, and bone mineral density analysis with dual-energy X-ray absorptiometry (DXA) is only rarely performed. We report the intervention methods suggested by pharmacists and describe their efficacy. Patients who visited the outpatient clinic of the General Medicine Department of Ogaki Municipal Hospital and received steroids were enrolled. The rates of DXA implementation and compliance with GIO pharmacotherapy guidelines before and after pharmacist to physician-suggested interventions were compared. Guideline compliance was defined as prescription of osteoporosis drugs to patients with a score of ≥3. Administered prophylaxes and bone mineral density were subsequently assessed. The before and after intervention DXA rates were 1% (1/100 patients) and 96.0% (96/100 patients; P<0.01), respectively. Overall, 96.9% (93/96) of the patients met the GIO criteria for pharmacotherapy initiation (score ≥3), and the guideline compliance rates before and after the intervention were 39.8% (37/93) and 93.5% (87/93; P<0.01), respectively. Of the 56 patients who did not receive prophylaxis, 52 were recommended treatment, yielding an acceptance rate of 82.7% (43/52). Among the 37 patients receiving prophylaxis, 20 (54.1%) had a DXA-related young adult mean of ≤70%, of whom 11 (55.0%) agreed to drug therapy. The acceptance rate of pharmacotherapy recommendations for patients not receiving prophylaxis was higher than that for those receiving prophylaxis (P=0.03). Pharmacist-initiated interventions for GIO facilitates the administration of appropriate pharmacotherapy.
Assuntos
Absorciometria de Fóton , Conservadores da Densidade Óssea , Densidade Óssea , Glucocorticoides , Fidelidade a Diretrizes , Osteoporose , Farmacêuticos , Humanos , Densidade Óssea/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Feminino , Masculino , Idoso , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Pessoa de Meia-Idade , Conservadores da Densidade Óssea/administração & dosagem , Idoso de 80 Anos ou mais , AdultoRESUMO
Vincristine (VCR) is an important drug used in R-CHOP regimens for the treatment of non-Hodgkin's lymphoma. The purpose of this study was to examine whether the administration method affects the incidence of VCR-induced peripheral neuropathy. We investigated the ratio of VCR-induced peripheral neuropathy during rapid intravenous infusion and intravenous drip infusion. A total of 71 patients who had received six or more courses of R-CHOP from January, 2015 to December, 2016 at Komaki City Hospital and Ogaki Municipal Hospital were retrospectively investigated. Peripheral neuropathy was observed in 27/39 patients (69 %) and 24/32 (75 %) in rapid intravenous infusion and intravenous drip infusion of VCR, respectively (P = 0.79). Peripheral neuropathy was observed at a high frequency in this study. Additionally, there was no difference in frequency of peripheral neuropathy due to the difference in administration method. In both groups, the degree of peripheral neuropathy was grade 1 and grade 2 in most patients. However, in rapid intravenous infusion, grade 3 peripheral neuropathy was observed. Some cases required dose reduction and discontinuation in rapid intravenous infusion. In contrast, there were no discontinuing patients in the intravenous drip infusion. Therefore, it was suggested that intravenous drip infusion of VCR reduced serious peripheral neuropathy because the ratio requiring dose reduction and discontinuation was less than that in the rapid group. In conclusion, this study is informative as there are few reports focusing on the administration method of vincristine.
Assuntos
Linfoma não Hodgkin , Doenças do Sistema Nervoso Periférico , Doxorrubicina/efeitos adversos , Humanos , Infusões Intravenosas , Linfoma não Hodgkin/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/patologia , Estudos Retrospectivos , Vincristina/efeitos adversosRESUMO
This study aimed to identify the overall survival prolongation index in patients who received paclitaxel plus ramucirumab as second line chemotherapy for human epidermal growth factor receptor (HER) 2-negative advanced/ recurrent gastric cancer (AGC). We included 77 patients who underwent second line chemotherapy (paclitaxel plus ramucirumab) for AGC at our institution between January 2015 and September 2020. To determine factors associated with survival, univariate and multivariate analyses were performed, and hazard ratios and their 95% confidence intervals (95% CI) were calculated. In the multivariate analysis, grade ≥1 neutropenia (yes) and the number of anti-cancer drugs used (≥5) were independently and significantly associated with survival. Compared to the patients without grade ≥1 neutropenia, patients with grade ≥1 neutropenia had a survival hazard ratio of 0.455 (95% CI: 0.214-0.966; p = 0.040). The median second line treatment durations in patients with grade ≥1 neutropenia (n = 54) and in those without grade ≥1 neutropenia (n = 23) were 133 days (95% CI, 98-190 days) and 70 days (95% CI, 41-128 days), respectively (log-rank test, p = 0.026). This study demonstrated that AGC patients with initial neutropenia may benefit from paclitaxel plus ramucirumab therapy.
Assuntos
Neoplasias Gástricas , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel , Prognóstico , Receptor ErbB-2 , Neoplasias Gástricas/tratamento farmacológico , RamucirumabRESUMO
We retrospectively evaluated the incidence of skin immune-related adverse effects (irAEs) in patients treated with pembrolizumab (PMB) and explored and the relationship between skin irAEs and PMB efficacy. Thirty-two patients with non-small cell lung cancer treated with PMB between April 2017 and May 2018 were enrolled. The patients were separated into two groups, namely, skin irAEs and no-skin irAEs group. We investigated the ratio and degree of express skin irAEs, period of skin irAEs and treatment, and the PFS between the two groups. Additionally, we evaluated the PFS between the irAE and no-irAEs groups. The median patient age was 76.5 (range 56-92) years. The European Cooperative Oncology Group Performance Status (ECOG PS) score of 26, 5, and 1 was 0-1, 2, and 3, respectively. The male/female ratio was 23/9. In terms of clinical stages, 6, 21, and 5 patients were in stages III and IV, and postoperative relapse, respectively. Skin irAEs were observed in 10 patients (31%). The progression-free survival of patients with skin irAEs (median, 390 days) was longer than that of patients without skin irAEs (median, 128.5 days). Overall, we suggested a significant association between skin irAEs and the efficacy of PMB in treating non-small cell lung cancer. As skin irAEs can be an indicator of treatment efficacy, it is important for medical staff, including pharmacists, to closely observe these adverse events.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Anormalidades da Pele/etiologia , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Pele/imunologia , Resultado do TratamentoRESUMO
This study aimed to clarify the relationship between neutropenia and progression-free survival (PFS) under palbociclib treatment for advanced/recurrent breast cancer and the risk factors for severe neutropenia. We retrospectively identified 37 patients who received palbociclib for advanced breast cancer at Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and June 2020. Kaplan-Meier log-rank test was used to compare PFS (mild [neutrophil count 1,000-2,000/mm 3 ] versus severe [neutrophil count <500-1,000/mm³]). Multivariate analysis was performed to evaluate the relationships between baseline patient characteristics and severe neutropenia development. There were three, four, 25, and five cases with grade 1, 2, 3, and 4 neutropenia, respectively. Median PFS in patients who developed severe neutropenia (n = 30) and those who did develop mild neutropenia (n = 7) was 176 days (range: 62-894 days) and 91 days (range: 19-384 days), respectively (log-rank test, p = 0.005). Severe neutropenia was independently associated with pre-treatment neutrophil count (odds ratio: 27.700; p =0.007). Severe neutropenia is more likely to occur with a pre-treatment neutrophil count of less than 3,680 mm³. Neutropenia prolongs PFS under palbociclib treatment, suggesting management of AEs and patient education as highly important, especially to prevent drug interruption/dose reduction of palbociclib due to these AEs.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/induzido quimicamente , Piperazinas/uso terapêutico , Intervalo Livre de Progressão , Piridinas/uso terapêutico , Idoso , Neoplasias da Mama/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Neutropenia/mortalidade , Estudos RetrospectivosRESUMO
Long-term azacitidine (AZA) treatment is necessary for its maximal therapeutic effect. This study examined the continuity and efficacy of AZA treatment in real-world use. We conducted a retrospective study in 38 patients who had completed AZA treatment at the Ogaki Municipal Hospital between April 2011 and August 2019. The median number of AZA received cycles was 4. The number of AZA treatment cycles received was 1-3 cycles in 15 (39.5%), 4-6 cycles in 15 (39.5%), and ≥ 7 cycles in 8 (21.1%). The most common reason for discontinued AZA treatment was infection. Overall response rate was 33.3% in patients with discontinued AZA use (< 4 cycles) and 56.5% in patients with continued AZA (≥ 4). Median overall survival (OS) was 124 (15-529) days and 391 (132-2,825) days in the respective groups (p<0.01). The presence of peripheral blood blasts (PBs) was a prognostic factor for continuation of treatment (p =0.03). Discontinued AZA treatment due to infection (p <0.01), and PBs (p =0.03) were unfavourable prognostic factors for OS. Long-term AZA use is beneficial for improvement and survival. Infection control and presence of PBs were important factors for continuing AZA. These data support the idea of long-term continued treatment with AZA for optimal benefit to patients.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Continuidade da Assistência ao Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Feminino , Humanos , Infecções/complicações , Infecções/epidemiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
This retrospective study compares the economic superiority of palbociclib versus everolimus for advanced and recurrent breast cancer. Furthermore, we investigated the safety and treatment continuity of palbociclib and everolimus regimens. Expected costs were calculated based on data from patients with advanced and recurrent breast cancer who were treated with palbociclib and everolimus. The progression-free survival (PFS) from the PALOMA-3 clinical trial and BOLERO-2 clinical trial was used to evaluate the therapeutic efficacy of the regimens. The cost-effectiveness ratio of each chemotherapy agent was calculated by dividing the expected cost by the progression-free survival (PFS). The cost-effectiveness ratio per month was JPY 391,551.3/PFS for palbociclib and JPY 488,690.5/PFS for everolimus (p=0.627). The incremental cost-effectiveness ratio per month of everolimus to palbociclib was JPY 100,133.7/PFS. For patients receiving everolimus, adverse drug reactions included stomatitis (77.3%), rash (59.1%) and leukopenia (59.1%). For patients receiving palbociclib, neutropenia (69.2%), leukopenia (69.2%) and anemia (30.8%) occurred. In terms of discontinuation owing to adverse events (AEs), pneumonitis, thrombocytopenia, edema, fatigue, and neutropenia were experienced in the everolimus group. The cost-effectiveness of everolimus and palbociclib are equivalent, but since the prevalence of AEs is high in patients receiving everolimus, its AE management is important.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Everolimo/economia , Everolimo/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Piperazinas/economia , Piperazinas/uso terapêutico , Piridinas/economia , Piridinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Everolimo/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Piridinas/efeitos adversosRESUMO
S-1 and cisplatin therapy (SP therapy) is widely used as the first-line of advanced/recurrent gastric cancer. However, severe neutropenia is often observed (40%) during this therapy. Therefore, the risk management of neutropenia is important. From September 2014 to April 2017, we investigated 76 patients who underwent SP therapy as primary treatment for advanced/recurrent gastric cancer at Ogaki Municipal Hospital. Risk factors for grade 3/4 neutropenia were examined by univariate and multivariate analyses. In SP therapy, 19 patients (25%) experienced grade 3/4 neutropenia. The results of multivariate analysis of factors with p <0.05 in the univariate analysis indicated that less than 10.6 g/dL of the haemoglobin value before the course at the lowest neutrophil count (odds ratio: 7.900; 95% CI: 1.280-48.60; p = 0.026), more than six courses of the total course (odds ratio: 9.13; 95% CI: 2.13-39.1; p = 0.003), and less than 3140 m2 neutrophil counts (odds ratio: 5.33; 95% CI: 1.47-19.3; p = 0.011) before chemotherapy were risk factors of grade 3/4 neutropenia. A low haemoglobin value before the course at the lowest neutrophil count was revealed as a risk factor causing severe neutropenia in SP therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Neoplasias Gástricas/complicações , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Combinação de Medicamentos , Feminino , Hemoglobinas/análise , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neutrófilos/efeitos dos fármacos , Ácido Oxônico/administração & dosagem , Fatores de Risco , Neoplasias Gástricas/tratamento farmacológico , Tegafur/administração & dosagemRESUMO
Vitamin (V) K deficiency may cause severe bleeding tendencies, which necessitates extreme caution. We report a case of a 30-year-old man diagnosed with VK deficiency of unknown etiology. He was treated with intravenous menatetrenone three times a week in an outpatient setting for about 1 year and 9 months. Eventually, he developed an allergic reaction to intravenous menatetrenone and was under steroid therapy. In order to reduce his hospital visits and discontinue steroid use, the pharmacist proposed to change the method of menatetrenone administration from intravenous to oral (high dose). The change in treatment method has greatly improved the patient's quality of life.
Assuntos
Hemostáticos/efeitos adversos , Hemostáticos/uso terapêutico , Vitamina K 2/análogos & derivados , Deficiência de Vitamina K/terapia , Administração Intravenosa , Administração Oral , Adulto , Hipersensibilidade a Drogas/tratamento farmacológico , Hemostáticos/administração & dosagem , Humanos , Masculino , Qualidade de Vida , Esteroides/uso terapêutico , Vitamina K 2/administração & dosagem , Vitamina K 2/efeitos adversos , Vitamina K 2/uso terapêuticoRESUMO
For patients with advanced/recurrent colorectal cancer, the trifluridine/tipiracil combination tablet (TAS 102) and regorafenib are last-line treatments. This study aimed to clarify prognostic factors in patients receiving last-line chemotherapy. Between April 2014 and December 2016, 47 patients received last-line chemotherapy at Ogaki Municipal Hospital, Japan. The primary outcome was overall survival. To determine factors associated with survival, those considered significant in the univariate analysis (p <0.10), were entered into a multivariate Cox proportional hazards model. KRAS type and the use of opioid formulations were independently and significantly associated with survival in the multivariate analysis. For patients with KRAS-wild relative to KRAS-mutation cancers, the hazard ratio for death was 0.478 (95% CI, 0.249-0.919; p = 0.03). For patients taking opioid formulations, relative to those not, the hazard ratio for death was 3.557 (95% CI, 1.032-12.257; p = 0.04). The median overall survival duration for patients with KRAS-wild (n = 24) and KRAS-mutation (n = 23) cancers were 223.5 days (range: 115-703) and 154 days (range: 51-503), respectively (p = 0.05). This finding provides a useful index to make an early decision on discontinuation of treatment and to guide decisions around agents to use in last-line chemotherapy.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Dor do Câncer/tratamento farmacológico , Neoplasias Colorretais/genética , Intervalo Livre de Doença , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Análise de SobrevidaRESUMO
As a result of the RAINBOW trial, ramucirumab plus paclitaxel was established as a second-line treatment of advanced gastric cancer. Regarding the safety of ramucirumab plus paclitaxel in the Japanese, a subgroup analysis of the RAINBOW trial was conducted. The incidence of neutropenia was higher in Japanese patients. However, information is lacking concerning the safety of ramucirumab after marketing in Japanese patients. Therefore, the aim of this study was to evaluate the safety of ramucirumab in Japanese patients with advanced gastric cancer. The inclusion criteria were patients diagnosed with advanced gastric cancer who had commenced treatment with ramucirumab plus paclitaxel or paclitaxel only at Ogaki Municipal Hospital (Gifu, Japan) between January 2015 and December 2016. There were 26 patients in the ramucirumab plus paclitaxel group and 22 patients in the paclitaxel only group. Treatment-related adverse events were documented in 100.0% of the patients in the ramucirumab plus paclitaxel group (Grade 3-4, 73.1%) and 90.9 % of the patients in the paclitaxel only group (Grade 3-4, 45.5 %). The most frequently observed adverse event in both treatment groups was anemia. The second common adverse event was neutropenia. The incidence of neutropenia of Grade ≥3 was significantly higher in the ramucirumab plus paclitaxel group than in the paclitaxel only group. In conclusion, the incidence of neutropenia is high. However, we believe that ramucirumab plus paclitaxel can be safely administered.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Gástricas/sangue , RamucirumabRESUMO
Elucidating the factors influencing severe neutropenia could aid in earlier management of neutropenia during oral trifluridine-tipiracil (TAS-102) chemotherapy in advanced and recurrent colorectal cancer (CRC). This study was conducted to assess the risk of TAS-102-induced grade 3 or more neutropenia. Between August 2014 and July 2017, 60 patients underwent oral TAS-102 monotherapy at Ogaki Municipal Hospital, Japan. The patients were divided into two groups based on the development of grade 3 or more neutropenia (9 patients) or not (51 patients). Risk factors for grade 3 or more neutropenia were examined by univariate and multivariate analyses. Creatinine clearance rate (CrCl) before TAS-102 administration significantly correlated with the incidence of Grade 3 or more neutropenia after TAS-102 administration (odds ratio 6.5, 95% confidence interval 1.14-30.00; p = 0.02). Multivariate analysis revealed that a CrCl of lower than 57.1 mL/min before TAS-102 administration (odds ratio 54.06, 95% confidence interval 2.14-1364.2; p = 0.02) was an independent risk factor significantly contributing to the development of grade 3 or more neutropenia, induced by TAS-102. CrCl < 57.1 mL/min in patients with advanced and recurrent CRC who underwent TAS-102 chemotherapy was associated with grade 3 or more neutropenia.
Assuntos
Neoplasias Colorretais/complicações , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Trifluridina/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/tratamento farmacológico , Creatinina/sangue , Combinação de Medicamentos , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neutrófilos , Pirrolidinas , Estudos Retrospectivos , Fatores de Risco , Timina , Trifluridina/uso terapêutico , Uracila/análogos & derivadosRESUMO
BACKGROUND/AIM: The effect of oral trifluridine-tipiracil (TAS-102)-induced neutropenia on survival of patients with advanced/recurrent colorectal cancer was investigated. PATIENTS AND METHODS: Between August 2014 and May 2016, 41 patients underwent TAS-102 monotherapy at Ogaki Municipal Hospital. Risk factors for survival were examined by univariate and multivariate analyses. RESULTS: In 41 patients, mild neutropenia (grade 1-2) occurred in 10 patients (24.4%), severe neutropenia (grade 3-4) occurred in 13 (31.7%), and 18 (43.9%) did not experience neutropenia. The median overall survival times in the absent, mild, and severe groups were 120 days (95% confidence interval [CI], 67-179), 184 days (95% CI, 94-274), and 299 days (95% CI, 192-404), respectively (p = 0.045). In patients with severe neutropenia, the death hazard ratio was 0.442 (95% CI, 0.201-0.974; p = 0.042). CONCLUSION: In patients with advanced/recurrent colorectal cancer, TAS-102-induced severe neutropenia was associated with superior survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neutropenia/sangue , Neutropenia/induzido quimicamente , Trifluridina/uso terapêutico , Uracila/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/sangue , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Pirrolidinas , Fatores de Risco , Análise de Sobrevida , Timina , Trifluridina/administração & dosagem , Uracila/administração & dosagem , Uracila/uso terapêuticoRESUMO
We retrospectively studied the safety of trifluridine/tipiracil combination tablet (TAS-102) monotherapy in patients with advanced and recurrent colorectal cancer. Adverse events to TAS-102 monotherapy were observed in 22 out of 23 cases (95.7%). The most frequent adverse events were neutropenia (69.6%), nausea (53.2%), and malaise (30.4%). Treatment was postponed in 54 (59.3%) out of 91 courses, and in 34 (66.7%) of these 54 courses, the delay in treatment was due to bone marrow suppression. Seven patients with peritoneal metastases suffered from nausea, whilst none of the patients without peritoneal metastases had nausea (p = 0.0139). Nausea and vomiting during a previous chemotherapy cycle was significantly associated with nausea after TAS-102 treatment (p = 0.0007), and the treatment cycles were significantly longer in patients with grade 3 or 4 neutropenia (p = 0.0061). Our results suggest that the incidence of nausea was higher in patients treated with TAS-102. Therefore, it is important to inform patients of the risk of these toxicities and to provide enhanced supportive care. Moreover, we recommend that, for patients with repeated treatment postponement due to neutropenia, the dosage should be fixed based on therapeutic efficacy and prognosis.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Trifluridina/uso terapêutico , Uracila/análogos & derivados , Adulto , Idoso , Medula Óssea/efeitos dos fármacos , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/epidemiologia , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Segurança do Paciente , Pirrolidinas , Estudos Retrospectivos , Comprimidos , Timina , Uracila/uso terapêutico , Vômito/induzido quimicamente , Vômito/epidemiologiaRESUMO
Neutropenia may develop as an adverse event in patients with multiple myeloma receiving lenalidomide (LEN) plus dexamethasone (DEX) therapy. In the present study, we examined the risk factors associated with grade 3/4 neutropenia during the first cycle of LEN plus DEX therapy. We observed that hemoglobin level (≤ 8.5 g/dl) was a significant risk factor for grade 3/4 neutropenia during the first cycle of therapy (odds ratio: 19.40; 95% confidence interval: 2.68-141.00; p < 0.01). thus, our findings suggest that determining the hemoglobin level could be useful in the risk management for neutropenia in patients receiving LEN plus DEX therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Mieloma Múltiplo/complicações , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/administração & dosagem , Feminino , Hemoglobinas/metabolismo , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Fatores de Risco , Talidomida/administração & dosagem , Talidomida/análogos & derivadosRESUMO
This study was retrospectively carried out to compare the efficacy of echinocandins such as micafungin (MCFG) and caspofungin (CPFG) in the treatment of antibiotic-unresponsive febrile patients with hematologic malignancies. A total of 163 patients received either MCFG or CPFG. We evaluated the efficacy of echinocandin against fever decline in all patients. Fever decline, defined as a body temperature of less than 37.5 °C sustained for more than 48 h without scheduled antipyretic medication. Efficacy assessments showed that the incidence of fever decline was not significantly different between the MCFG and CPFG groups (P=0.599). The median number of days from the start of echinocandin administration to fever decline was 5 in both the MCFG and CPFG groups. Multivariate analysis showed that the use of anti-MRSA drugs (HR, 0.64; 95%CI, 0.45-0.90; P=0.011) and a change from echinocandins to voriconazole or liposomal-amphotericin B (HR, 0.50; 95%CI, 0.30-0.74; P<0.001) are significant risk factors for sustained fever. A significant difference (P=0.002) in incidence of fever decline was however associated with differences in the timing of anti-MRSA drug administration. The median number of days from the start of echinocandin administration to fever decline was 5 when administration of the anti-MRSA drug occurred "simultaneously or prior to echinocandin start" and 11 in the "next day or later of echinocandin start" group. In other words, starting anti-MRSA drug treatment after echinocandin treatment is a risk factor. In conclusion, MCFG and CPFG have similar efficacy as empirical antifungal agents in the treatment of antibioticunresponsive febrile patients with hematopoietic malignancies.
Assuntos
Antifúngicos/uso terapêutico , Equinocandinas/uso terapêutico , Febre/tratamento farmacológico , Febre/etiologia , Neoplasias Hematológicas/complicações , Lipopeptídeos/uso terapêutico , Micoses/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Caspofungina , Farmacorresistência Fúngica , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Micafungina , Pessoa de Meia-Idade , Micoses/complicações , Estudos Retrospectivos , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Adulto JovemRESUMO
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib, erlotinib and afatinib are standard first-line treatments for EGFR gene mutation-positive non-small cell lung cancer. The present study aimed to compare the cost-effectiveness of using erlotinib, afatinib or gefitinib. The safety of EGFR-TKIs was also investigated. Expected costs were calculated based on data from patients with advanced EGFR mutation-positive non-small-cell lung cancer who were treated with gefitinib, erlotinib or afatinib. Literature was collected to obtain the necessary clinical information for calculating the probability and the validity of each chemotherapy. Median survival time (MST) was used to evaluate the therapeutic effect of the regimens. The cost-effectiveness ratio was calculated using expected costs and MSTs for the three regimens. The cost-effectiveness ratio per month was JPY 386,859.4/MST for afatinib, JPY 264,788.7/MST for gefitinib and JPY 397,039.9/MST for erlotinib. Significant differences were observed between the three groups (p<0.001). The incremental cost-effectiveness ratio (ICER) of gefitinib compared with afatinib per month was JPY 122,070.7/MST. The ICER of gefitinib compared with erlotinib was JPY -69,605.9/MST. Adverse effects of Grade 3 and higher, including diarrhoea (28.6%) and paronychia (14.3%) were observed in the afatinib treatment group. Paronychia (23.1%) was observed in the erlotinib treatment group, while none were observed in the gefitinib treatment group. These findings demonstrate that gefitinib is more cost effective in comparison with the afatinib and erlotinib regimens, although the afatinib and erlotinib regimens were well-tolerated and produce sufficient effects.
RESUMO
It is a well known fact that the injured PNS can successfully regenerate, on the other hand, the CNS such as retinal ganglion cell (RGC) axons of adult mammals is incapable of regeneration. After injury, RGC axons rapidly degenerate and most cell bodies go through the process of cell death, while glial cells at the site of injury undergo a series of responses which underlie the so-called glial scar formation. However, it has become apparent that RGCs do have an intrinsic capacity to regenerate which can be elicited by experimental replacement of the inhibitory glial environment with a permissive peripheral nerve milieu. Schwann cells are a major component of the PNS and play a role in regeneration, by producing various kinds of functional substances such as diffusible neurotrophic factors, extracellular matrix and cell adhesion molecules. RGC regeneration can be induced by cooperation of these substances. The contact of RGC axons to Schwann cells based upon the structural and molecular linkages seems to be indispensable for the stable and successful regeneration. In addition to cell adhesion molecules such as NCAM and L1, data from our laboratory show that Schwann cells utilize short focal tight junctions to provide morphological stabilization of the contact with the elongating axon, as well as a small scale of gap junctions to facilitate traffic of substances between them. Moreover, our results show that modifications of functional properties in neighboring glial cells of optic nerve are induced by transplantation of Schwann cells. Astrocytes usually considered to form a glial scar guide the regenerating axons in cooperation with Schwann cells. A decrease of the oligodendrocyte marker O4 and migration of ED-1 positive macrophages is observed within the optic nerve stump. Accordingly, RGC regeneration is not a simple phenomenon of axonal elongation on the Schwann cell membrane, but is based on direct and dynamic communication between the axon and the Schwann cell, and is also accompanied by changes and responses among the glial cell populations, which may be partly associated with the mechanisms of optic nerve regeneration.
Assuntos
Regeneração Nervosa/fisiologia , Nervo Óptico/fisiologia , Células Ganglionares da Retina/fisiologia , Células de Schwann/fisiologia , Animais , HumanosRESUMO
The authors report a patient with an axonal Guillain-Barré syndrome (acute motor axonal neuropathy) associated with anti-GM1 antibody after Haemophilus influenzae infection. The result of ELISA inhibition studies and cytochemical staining with cholera toxin suggest the presence of a GM1-like structure on the surface of H. influenzae isolated from the patient. A particular strain of H. influenzae may have a GM1-like structure and may elicit an axonal Guillain-Barré syndrome.
Assuntos
Gangliosídeo G(M1)/imunologia , Infecções por Haemophilus/complicações , Haemophilus influenzae/imunologia , Polirradiculoneuropatia/imunologia , Adulto , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino , Condução Nervosa/fisiologia , Polirradiculoneuropatia/complicações , Polirradiculoneuropatia/fisiopatologiaRESUMO
Gap junctions are intercellular channels which mediate the traffic of ions and a variety of molecular messengers between contiguous cells. Here, we report on the possibility that atypical gap junctions develop between heterologous tissues, such as regenerating nerve axons and Schwann cells, during peripheral nerve regeneration in adult rats. After a complete transection and subsequent regeneration in the rat sciatic nerve distal segment, a small scale gap junction-like structure was observed between the regenerating axons and adjoining Schwann cells. Immunoelectron microscopy showed that one of the gap junctional proteins, connexin32, was located at a small region of contact between the axon and Schwann cells. Biocytin, a small molecular weight dye, was transported from regenerating axons into adjoining Schwann cells. The present findings suggest that regenerating axons communicate directly with adjacent Schwann cells through small gap junctions, which may play a role in the mechanism of regeneration following nerve transection.