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1.
Pediatr Blood Cancer ; 66(11): e27953, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31393093

RESUMO

BACKGROUND: Pediatric patients with high-risk, relapsed, or refractory solid tumors have a poor prognosis. We have previously reported a dose-finding experience of high-dose chemotherapy consisting of thiotepa and melphalan ("double-conditioning regimen"). Using doses derived from that study, we have treated patients since 2005. We now report a retrospective review of patients treated by this fixed dose. PROCEDURE: We reviewed 50 patients (median 4 years; range 0-15 years) with high-risk or relapsed/refractory solid tumors treated by this dose-fixed, double-conditioning regimen from April 2005 to May 2014. Doses were thiotepa 800 mg/m2 and melphalan 280 mg/m2 for children ≥2 years of age, and 32 mg/kg and 6 mg/kg, respectively, for children <2 years of age. Further, doses were reduced according to creatinine clearance with poor renal function. RESULTS: Nonhematological toxicity was mainly gastrointestinal-grade 3 mucositis (n = 41) and grade 3-4 diarrhea (n = 10). Neurological, renal, and endothelial cell toxicity and sinusoidal obstruction syndrome were not observed. There were two toxic deaths (interstitial viral pneumonia). This regimen demonstrated antitumor activity against several types of tumors. Although the frequency of gastrointestinal toxicity was high, other severe toxicity was not observed. CONCLUSIONS: Our double-conditioning regimen was very well tolerated and demonstrated antitumor activity. We are moving forward with multi-institutional trials now.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/terapia , Transplante de Células-Tronco de Sangue Periférico , Terapia de Salvação , Condicionamento Pré-Transplante/métodos , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Creatinina/sangue , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Estudos de Viabilidade , Feminino , Seguimentos , Gastroenteropatias/induzido quimicamente , Doenças Hematológicas/induzido quimicamente , Humanos , Lactente , Recém-Nascido , Doenças Pulmonares Intersticiais/etiologia , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Neoplasias/tratamento farmacológico , Pneumonia Viral/etiologia , Estudos Retrospectivos , Risco , Tiotepa/administração & dosagem , Tiotepa/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo
2.
J Neurooncol ; 145(1): 57-63, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432377

RESUMO

PURPOSE: An increased incidence in hematologic toxicity has been reported with the addition of bevacizumab to lomustine for patients with recurrent or progressive high grade gliomas (HGG). Data regarding incidence of toxicity with combination bevacizumab and carmustine is limited. The purpose of this study is to compare toxicity of single agent carmustine and carmustine plus bevacizumab for patients with HGGs. METHODS: This single center retrospective study at Memorial Sloan Kettering Cancer Center included pathologically confirmed HGG with age ≥ 18 years who received carmustine between January 2003 and May 2017. RESULTS: Sixty-five patients with HGGs collectively received 110 doses of BCNU during the specified time period. Sixteen patients received single agent BCNU (30 doses); 49 patients received combination bevacizumab with BCNU (80 doses). There was no significant difference in incidence or grade of toxicity between single agent and combination therapy with respect to hepatotoxicity, leukopenia, lymphopenia, neutropenia, anemia, and thrombocytopenia. Rates of grade 3 and 4 neutropenia (20% vs 13.8%, p = 0.55) and thrombocytopenia (23.3% vs 23.8%, p = 1) did not differ between single agent BCNU versus combination therapy. When stratified based on dose ( < 150 mg/m2, 150 mg/m2, > 150 mg/m2), there was no statistically significant difference between the two groups with respect to grade 3 and 4 neutropenia or thrombocytopenia. CONCLUSIONS: This is the first study to report the toxicity of carmustine with or without bevacizumab for the treatment of recurrent and refractory HGG. The addition of bevacizumab to carmustine did not increase incidence or grade of hematologic toxicity when compared to single agent carmustine.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Glioma/tratamento farmacológico , Doenças Hematológicas/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Neoplasias Encefálicas/patologia , Carmustina/administração & dosagem , Feminino , Seguimentos , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Adulto Jovem
3.
Hematology ; 24(1): 552-558, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31315553

RESUMO

Objectives: To analyze the efficacy and safety of decitabine combined with low/reduced-dose chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients unfit for intensive therapy and to investigate the early prognostic indicators for these patients. Methods: The eligible patients treated with decitabine-based chemotherapy were retrospectively analyzed. Responses and long-term survival were calculated and their correlation with clinical characteristics was analyzed. Minimal residual disease (MRD) detected by flow cytometry (FCM) after the induction therapy was measured, and the association with prognosis was explored. Results: Fifty-five newly diagnosed AML patients were enrolled. The overall response rate (ORR) was 80.0%, with a complete remission (CR) rate of 63.64% and partial remission (PR) rate of 16.36%. Grade 4 hematological toxicity was common, and the incidence of infections was 83.64%, with 18.18% of patients suffered from severe infections. No serious bleeding or non-hematological adverse events occurred. Treatment-related mortality was 3.64%. The median overall survival (OS) and disease-free survival (DFS) were 17.0 (13.7-20.3) months and 17.0 (10.2-23.8) months, respectively. Multivariate analysis showed that an advanced age (≥ 60 years) and higher MRD (≥ 1.34%) after induction therapy were adverse prognostic factors for patients who had achieved CR. Conclusions: Decitabine-based chemotherapy may be a suitable therapeutic alternative for newly diagnosed AML patients who are unfit for intensive chemotherapy. An advanced age (≥ 60 years) and higher MRD (≥ 1.34%) were considered adverse prognostic factors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/patologia , Aclarubicina/administração & dosagem , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Decitabina/administração & dosagem , Decitabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Doenças Hematológicas/induzido quimicamente , Mepesuccinato de Omacetaxina/administração & dosagem , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
4.
Int J Clin Oncol ; 24(12): 1574-1581, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31309381

RESUMO

BACKGROUND: The efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) plus gemcitabine (GEM) in elderly Japanese patients with pancreatic cancer remain unclear. Therefore, we prospectively investigated the tolerability and efficacy of nab-PTX + GEM in Japanese patients aged ≥ 75 years with non-curatively resectable pancreatic cancer. METHODS: We treated eligible patients (n = 27) with nab-PTX + GEM until disease progression, appearance of adverse events, or withdrawal of consent. The primary endpoints included adverse events as well as dosing- and survival-related parameters. RESULTS: The rates of 2-cycle completion were 48.1% for nab-PTX and 55.6% for GEM; the relative dose intensities for the 7th (median) treatment cycle were 65.1% and 74.1%, respectively, whereas the dose-reduction rates were 81.5% and 48.1%, respectively. Grade 3 or higher hemotoxicity was observed in 14 of 27 subjects (51.9%); moreover, 22% experienced grade ≥ 3 peripheral nerve disorder and 1 patient (3.7%) died owing to chemotherapy-related interstitial pneumonia. The disease control rate was 92.6% (25/27), while the median progression-free and overall survival times were 7 and 10.3 months, respectively. CONCLUSION: The nab-PTX + GEM regimen is as efficacious in elderly patients who meet certain criteria as it is in previously reported non-elderly patients. The regimen is feasible with appropriate dose adjustments and attention to adverse events. TRIAL REGISTRATION: Clinical trial registration number: UMIN000018907.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Estudos de Viabilidade , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Masculino , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/cirurgia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Prospectivos , Resultado do Tratamento
5.
Hematology ; 24(1): 498-506, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31221030

RESUMO

OBJECTIVES: The addition of lenalidomide (LEN) to azacitidine (AZA) may further improve the outcomes of acute myeloid leukemia (AML) patients as well as patients with high-risk myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients although the evidence for this combination treatment is still relatively limited. This meta-analysis aimed to evaluate efficacy and adverse effects of AZA plus LEN for the treatment of patients with high-risk MDS, AML or CMML. METHODS: The current study systematically identified all cohort studies of patients with AML and/or MDS and/or CMML who received AZA in combination with LEN that reported the overall complete remission (CR) rate and/or overall response rate (ORR). A DerSimonian-d random-effects model with double arcsine transformation was used for the pooled rates and 95% confidence interval (CI) of the all outcomes. RESULTS: A total of 10 studies with 406 patients were identified and included into the meta-analysis. The pooled CR rate after the treatment with AZA-plus-LEN regimen was 33.0% (95% CI, 27.7%-38.7%, I2 = 18%) while the pooled ORR was 49.9% (95% CI, 38.4%-61.5%, I2 = 72%). Nonetheless, adverse events including grade 3-4 neutrophil toxicity events, platelet toxicity events and febrile neutropenia were common with AZA-plus-LEN regimen. CONCLUSIONS: The current study may serve as a preliminary data to suggest that the addition of LEN may offer incremental benefit to patients with high-risk MDS, AML and CMML. However, randomized-controlled studies that directly compare the efficacy and adverse events of AZA-plus-LEN regimen versus AZA monotherapy are still needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Estudos de Coortes , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Hematology ; 24(1): 507-515, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31242832

RESUMO

Background: Approximately, one-third of adult patients with acute myeloid leukemia (AML) are refractory to initial induction chemotherapy and relapse occurs in most patients who achieve remission. This study evaluates the efficacy of decitabine in the management of refractory or relapsed AML. Methods: After literature search in electronic databases (Google Scholar, Embase, Ovid, and PubMed) studies were selected by following pre-determined eligibility criteria. Random-effects meta-analyses were performed to achieve effect sizes of complete remission (CR) rate, response rate (RR), and median survival after therapy. Subgroup analyses were performed with regards to use of decitabine with either epigenetics-based therapy, molecular therapy or chemotherapy. Results: Twenty studies were included (310 patients; age 55.1 years [95% confidence interval (CI): 43.8, 66.4]; 57% [52%, 63%] males). Overall RR was 46.1% [95% CI: 36.1%, 56.1%]. Overall CR rate was 23.5% [95% CI: 22.1%, 24.9%] but was 14.85% [95% CI: 3.8%, 25.9%] for decitabine with epigenetics-based therapies, 15.4% [95% CI: 6.7%, 24.0%] for decitabine with immunotherapy or molecular therapy, 34.8% [95% CI: 18.7%, 50.9%] for decitabine with chemotherapy, and 37.5% [36.4%, 38.7%] for decitabine with chemotherapy and molecular therapy. Median survival was 7.2 months [95% CI: 5.17, 9.3]. Major adverse events were neutropenia, nausea/vomiting, infections, fatigue, febrile neutropenia, diarrhea, thrombocytopenia, anemia, anorexia, leukopenia, hemorrhage, and hyperglycemia. Conclusion: Decitabine in combination with chemotherapy or molecular therapy has shown efficacious properties in refractory or relapsed AML patients.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Metilação de DNA/efeitos dos fármacos , Decitabina/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Terapia de Alvo Molecular , Terapia de Salvação , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , DNA (Citosina-5-)-Metiltransferase 1/antagonistas & inibidores , Decitabina/administração & dosagem , Decitabina/efeitos adversos , Decitabina/farmacologia , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacologia , Fadiga/induzido quimicamente , Neutropenia Febril/induzido quimicamente , Feminino , Gastroenteropatias/induzido quimicamente , Doenças Hematológicas/induzido quimicamente , Humanos , Hiperglicemia/induzido quimicamente , Imunoterapia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão
7.
Gynecol Oncol ; 154(1): 138-143, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31079832

RESUMO

OBJECTIVE: To evaluate hematologic adverse effect profiles associated with frontline platinum-based chemotherapy in ovarian cancer patients according to BRCA 1/2 mutational status. METHODS: Patients with high-grade serous ovarian cancer and a known BRCA mutational status who received in frontline 6 cycles of Carboplatin (AUC 5) plus Paclitaxel 175 mg/mq were retrospectively selected from our databases. Hematologic toxicity profiles of BRCA mutated patients were compared to non-mutated patients, according to EORTC Common Terminology Criteria for Adverse Events (CTCAE_4.02). RESULTS: Totally, 176 women of whom 58 (33%) were BRCA1/2 mutation carriers - 40 BRCA1 (69%) and 18 (31%) BRCA2 mutations carriers - and 118 (67%) non-carriers were identified. A significant higher frequency of thrombocytopenia (24% vs 5%; p < 0.001), anemia (21% vs 7%; p = 0.006) and neutropenia (62% vs 27%; p ≤0.001) was observed in BRCA mutated patients, resulting in a higher percentage of granulocyte-colony stimulating growth factors injection (12% versus 1%, p < 0.001) and dose delay (19% versus 27%, p = 0.005). The multivariate analysis confirmed that granulocyte-colony stimulating growth factors injection and dose delay were statistically significantly more frequent in BRCA mutated patients (OR 2.567, 95% CI 1.136-5.798, p = 0.035; OR 3.860, 95% CI 1.098-13.570, p = 0.023). Finally, the total number of hematologic adverse events compared between the two groups of patients during the entire treatment period showed a substantial higher rate of hematologic adverse events in BRCA mutated population. CONCLUSIONS: Germline BRCA 1/2 mutations are associated with a higher hematologic toxicity in patients with ovarian cancer who underwent platinum-based chemotherapy.


Assuntos
Cistadenocarcinoma Seroso/tratamento farmacológico , Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/genética , Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína BRCA1/genética , Proteína BRCA2/genética , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Estudos de Coortes , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Feminino , Predisposição Genética para Doença , Doenças Hematológicas/sangue , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Estudos Retrospectivos
8.
Malar J ; 18(1): 111, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940140

RESUMO

BACKGROUND: Primaquine (PQ) prevents relapses of vivax malaria but may induce severe haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Data on the safety of primaquine in infants are limited. METHODS: A retrospective, hospital-based cohort study of infants aged 1-12 months with vivax malaria was carried out in Timika, Papua province, Indonesia. Risks of admission, death and severe haematological outcomes within 30 days of first presentation were compared between infants who did and did not receive primaquine. Infants were not tested routinely for G6PD deficiency as per local guidelines. RESULTS: Between 2004 and 2013, 4078 infants presented to the hospital for the first time with vivax malaria, of whom 3681 (90.3%) had data available for analysis. In total 1228 (33.4%) infants were aged between 1 and 6 months and 2453 (66.6%) between 6 and 12 months of age. Thirty-three (0.9%) patients received low-dose primaquine (LDP), 174 (4.7%) received high-dose primaquine (HDP), 3432 (93.2%) received no primaquine (NPQ) and 42 patients received either a single dose or an unknown dose of primaquine. The risk of the Hb concentration falling by > 25% to less than 5 g/dL was similar in the LDP or HDP groups (4.3%, 1/23) versus the NPQ group (3.5%, 16/461). Three infants (1.4%) died following receipt of PQ, all of whom had major comorbidities. Seventeen patients (0.5%) died in the NPQ group. None of the infants had documented massive haemolysis or renal impairment. CONCLUSIONS: Severe clinical outcomes amongst infants treated with primaquine in Papua were rare. The risks of using primaquine in infancy must be weighed against the risks of recurrent vivax malaria in early life.


Assuntos
Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/epidemiologia , Malária Vivax/tratamento farmacológico , Primaquina/administração & dosagem , Primaquina/efeitos adversos , Feminino , Hemólise , Humanos , Indonésia/epidemiologia , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Análise de Sobrevida
9.
Ann Hematol ; 98(6): 1441-1447, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30874851

RESUMO

Pomalidomide dexamethasone is a standard of care for relapsed multiple myeloma (MM) patients who received at least two prior lines of therapy, including both lenalidomide and proteasome inhibitors (PI). We report here a real-life single-center series of 49 consecutive patients with relapsed and refractory MM treated with the triplet pomalidomide cyclophosphamide dexamethasone (PCD) combination. The median of prior lines of therapy was 3 and all patients were previously exposed to proteasome inhibitors and lenalidomide. The overall response rate was 76%, including 27% very good partial response or better. With a median follow-up of 16 months, the median progression-free survival (PFS) was 7.3 months and the median overall survival was not reached. Regarding safety, most frequent toxicity was hematologic, including 37% grade 3-4 cytopenias. Nine patients (18%) discontinued therapy due to adverse event. Our study confirms that PCD combination is feasible and results in favorable response rate and PFS in comparison with pomalidomide dexamethasone alone.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Terapia de Salvação , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Avaliação de Medicamentos , Substituição de Medicamentos , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Lenalidomida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Inibidores de Proteases/uso terapêutico , Recidiva , Estudos Retrospectivos , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/análogos & derivados
10.
Int J Clin Oncol ; 24(5): 557-566, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30875000

RESUMO

BACKGROUND: Radium-223 is a first-in-class targeted alpha therapy to prolong overall survival (OS) in castration-resistant prostate cancer with bone metastases (mCRPC). The aim of the present analysis was to assess the long-term safety with radium-223 in Japanese patients with mCRPC. METHODS: Patients with symptomatic mCRPC, ≥ 2 bone metastases and no known visceral metastases received up to 6 injections of radium-223 (55 kBq/kg), one every 4 weeks. Adverse events (AEs) considered to be related to radium-223 were reported until 3 years after the first injection. Pre-specified conditions, such as acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, primary bone cancer, or other primary malignancies, were reported regardless of causality. RESULTS: Of the 49 patients enrolled in the study, 44 (89.8%) entered the survival follow-up period and 33 (67.3%) died. Throughout the entire study, there were no reports of second primary malignancy or other pre-specified conditions. Eight patients (16.3%) experienced post-treatment drug-related AEs, which were all hematological (anemia and decreased lymphocyte, platelet, and white blood cell counts). No serious post-treatment drug-related AEs were reported. Updated median OS was 19.3 months (95% CI: 14.2, 28.5). CONCLUSIONS: In Japanese patients with symptomatic mCRPC and bone metastases, radium-223 had a favorable long-term safety profile with no second primary malignancies reported. Taken together with median OS, which was comparable to that in the pivotal phase III ALSYMPCA study, these results support continued benefit from radium-223 in Japanese patients with mCRPC.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias de Próstata Resistentes à Castração/radioterapia , Rádio (Elemento)/efeitos adversos , Rádio (Elemento)/uso terapêutico , Administração Intravenosa , Idoso , Anemia/induzido quimicamente , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Seguimentos , Doenças Hematológicas/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Lesões por Radiação/etiologia , Radioisótopos/administração & dosagem , Radioisótopos/efeitos adversos , Radioisótopos/uso terapêutico , Rádio (Elemento)/administração & dosagem
11.
Dis Model Mech ; 12(3)2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-30898970

RESUMO

Benzene exposure is associated with various hematological disorders, in particular leukemia. The reactive metabolite of benzene, 1,4-benzoquinone (BQ), generated in bone marrow, is suggested to be a key molecule in mediating benzene-induced hematotoxicity and carcinogenicity. However, its pathogenic role remains largely unknown due to a lack of suitable vertebrate whole-organism models. Here, we present an in vivo study to reveal the effect of BQ exposure on hematotoxicity in zebrafish. From embryonic stages to adulthood, BQ exposure suppressed erythroid and lymphoid hematopoiesis but led to abnormal accumulation of myeloid cells and precursors, which resembles benzene-induced cytopenia and myeloid dysplasia in humans. This myeloid expansion is caused by granulocyte, but not macrophage, lineage, emphasizing the significant role of lineage specificity in BQ-mediated hematopoietic toxicity. Analysis of the c-myb (also known as myb)-deficient mutant cmybhkz3 revealed that BQ induced neutrophilia in a c-myb-dependent manner, demonstrating that c-myb is a key intrinsic mediator of BQ hematotoxicity. Our study reveals that BQ causes lineage-specific hematotoxicity in zebrafish from embryonic stages to adulthood. Since c-myb is indispensable for BQ to induce neutrophilia, c-myb could serve as a potential drug target for reversing BQ hematotoxicity.


Assuntos
Benzoquinonas/toxicidade , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/patologia , Peixe-Zebra/metabolismo , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Embrião não Mamífero/citologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Hematopoese/efeitos dos fármacos , Estimativa de Kaplan-Meier , Mutação/genética , Células Mieloides/efeitos dos fármacos , Células Mieloides/metabolismo , Neutrófilos/metabolismo , Neutrófilos/patologia , Proteínas Proto-Oncogênicas c-myb/metabolismo , Teratogênios/toxicidade , Peixe-Zebra/embriologia
12.
Integr Cancer Ther ; 18: 1534735419833778, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30841763

RESUMO

This study aimed to evaluate the effect of lignin-derived polyphenolic composition BP-C3 on the efficacy and hematological toxicity of cyclophosphamide (CPA). Male and female Swiss-H derived mice bearing benzo[a]pyrene-induced soft tissue sarcomas were treated with CPA 300 mg/kg, BP-C3 75 mg/kg, or a combination. Tumor growth inhibition in male mice treated with CPA, BP-C3, or a combination of CPA and BP-C3 was significant and corresponded to 78%, 45%, and 82%, respectively, on day 21 after CPA administration on day 0. In female mice, tumor growth inhibition was 58%, -11%, and 35% when treated with CPA, BP-C3, or a combination of CPA and BP-C3, respectively. CPA administration resulted in significant hematological toxicity evidenced by a decreased white blood cell count on day 4 (2.43 ± 1.77 × 109/L in male mice and 1.19 ± 0.71 × 109/L in female mice) and anemia development on day 7 (6.55 ± 1.74 × 1012/L in male mice and 5.89 ± 2.24 × 1012/L in female mice). The red blood cell count measured on day 7 in animals treated with the combination of BP-C3 and CPA constituted 7.12 ± 1.17 × 1012/L and 7.36 ± 2.07 × 1012/L for male and female mice, respectively. The results of our study demonstrate the antitumor activity of BP-C3 in male mice bearing soft tissue sarcomas. Neither the antitumor activity nor the hematological toxicity of CPA were significantly influenced by BP-C3. A less pronounced effect of CPA on RBC count is demonstrated when this agent is given jointly with BP-C3.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Benzo(a)pireno/farmacologia , Ciclofosfamida/efeitos adversos , Ciclofosfamida/farmacologia , Doenças Hematológicas/induzido quimicamente , Polifenóis/farmacologia , Sarcoma/tratamento farmacológico , Animais , Feminino , Masculino , Camundongos
13.
Cad Saude Publica ; 35(2): e00091618, 2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30758455

RESUMO

Mercury is a metal found in the environment from natural and anthropogenic sources. It is highly toxic to ecosystems and living beings. Most human exposures come from ingestion of contaminated seafood, outgassing from dental amalgam or occupational exposure (e.g. gold mining), among other cases. Large populations are exposed to mercury, making it a very important issue from the public health perspective. Adverse health effects are commonly seen in the nervous system, but every organ is a potential target, such as the bone marrow. The main goal of this study was to assess the available evidence on human exposure to mercury and its hematological effects. A search strategy was constructed, including key terms (MeSH, text word and equivalents) for querying 2 repositories of master dissertation and PhD thesis (Fiocruz/ARCA and University of São Paulo) and 4 different electronic databases: BVS/LILACS, MEDLINE/PubMed, Scopus and TOXLINE/NIH, for articles published from 1950 to February 2018. There was no language restriction and a tool (EPHPP) was used to assess the quality of included studies. According to pre-established criteria, 80 studies were retrieved, all of them observational (48 case reports, 24 cross-sectional, 6 case series and 2 cohorts), comprising 9,284 people. Despite the fact that most exposed ones (6,012) had normal blood cell count and mercury hematological effects did not seem very usual (1,914 cases: 14 severe and 29 deaths), three studies reported association (ß) for anemia, lymphopenia, neutrophilia and basophilia. We concluded that the gathered information pointed to mercury hematotoxic effects, some of them may be serious and even fatal.


Assuntos
Exposição Ambiental/efeitos adversos , Doenças Hematológicas/induzido quimicamente , Intoxicação por Mercúrio/sangue , Mercúrio/efeitos adversos , Mercúrio/análise , Brasil , Contagem de Células , Monitoramento Ambiental , Doenças Hematológicas/sangue , Doenças Hematológicas/classificação , Testes Hematológicos , Humanos , Compostos de Mercúrio/envenenamento , Exposição Ocupacional/efeitos adversos
14.
J Infect Chemother ; 25(5): 351-354, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30711257

RESUMO

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients on steroid therapy for connective tissue diseases. The standard agent for primary PCP prophylaxis is trimethoprim/sulfamethoxazole (TMP-SMX), although this agent can cause common adverse reactions, including myelosuppression and renal toxicity, that result in cessation. Aerosolized pentamidine and oral atovaquone are alternatives for PCP prophylaxis. The efficacies of atovaquone, pentamidine, and TMP-SMX to prevent PCP in patients with connective tissue diseases have never been compared. METHODS: Hospitalized patients with connective tissue diseases who started steroid therapy and PCP prophylaxis were enrolled. PCP prophylaxis regimens were oral TMP-SMX, aerosolized pentamidine, or oral atovaquone. Information was retrospectively collected from medical records about laboratory findings, duration of PCP prophylaxis, and reasons for terminating PCP prophylaxis. RESULTS: Ninety-six patients received PCP prophylaxis. All of them were initially treated with TMP-SMX, but this was replaced during the study period with pentamidine in 33 patients and with atovaquone in 7. Forty-one (43%) patients discontinued TMP-SMX because of adverse events, and 5 (15%) also discontinued pentamidine. None of the patients discontinued atovaquone. The most frequent causes of TMP-SMX and pentamidine cessation were cytopenia (N = 15) and asthma (N = 2). The rates of continuing treatment with TMP-SMX, pentamidine, and atovaquone at one year after starting PCP prophylaxis were 55.3%, 68.6%, and 100%, respectively (P = 0.01). None of the patients developed PCP. CONCLUSION: Although TMP-SMX for PCP prophylaxis had to be discontinued in 43% of patients with connective tissue diseases, pentamidine and atovaquone were well tolerated.


Assuntos
Antibioticoprofilaxia/métodos , Doenças do Tecido Conjuntivo/complicações , Infecções Oportunistas/prevenção & controle , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/prevenção & controle , Administração por Inalação , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibioticoprofilaxia/efeitos adversos , Asma/induzido quimicamente , Asma/epidemiologia , Atovaquona/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/microbiologia , Pentamidina/uso terapêutico , Pneumonia por Pneumocystis/microbiologia , Estudos Retrospectivos , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adulto Jovem
15.
PLoS One ; 14(2): e0211708, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30759131

RESUMO

BACKGROUND: Hematologic abnormalities involving peripheral blood cell cytopenias are strong predictors of morbidity, mortality and poor antiretroviral therapy (ART) outcomes of HIV infected individuals. However, limited studies are conducted in resource-limited settings of sub-Saharan Africa that have addressed the magnitude and associated factors of cytopenias. This study aimed to investigate the magnitude and associated factors of cytopenias among ART naïve HIV infected adult Ethiopians. MATERIALS AND METHODS: A cross-sectional study was conducted among ART naïve HIV infected individuals attending at ART unit of Dessie Referral Hospital between November 01, 2015 and April 30, 2016. A total of 402 adults were included using consecutive sampling. Socio-demographic, clinical and laboratory data of patients were collected. The data were entered to Epi Info version 3.4.3 and analyzed using SPSS version 20 software (SPSS INC, Chicago, IL, USA). Factors associated with cytopenias were analyzed first using bivariate and then multivariate logistic regression models. An odds ratio with 95% confidence interval was used to measure the strength of association. For all statistical significant tests, the cut-off value was set at P<0.05. RESULTS: In this study, the overall magnitude of any cytopenia, anemia, leucopenia and thrombocytopenia were 63.4%, 43.5%, 24.4% and 18.7%, respectively. In multivariate logistic regression analysis, severe immunosuppression and WHO clinical stage IV HIV disease were significantly associated with increased prevalence of cytopenias. In addition, older age and younger age showed significant association with increased prevalence of anemia and leucopenia, respectively. CONCLUSION: Frequent occurrence of cytopenias was independently associated with severe immunosuppression and WHO clinical stage IV HIV disease. Further longitudinal multicenter studies are recommended to bolster the findings of this study in order to suggest the need of routine assessment and management of hematological abnormalities for optimal choice of initial antiretroviral agents and prevention of further morbidities.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Doenças Hematológicas/induzido quimicamente , Adolescente , Adulto , Fatores Etários , Idoso , Anemia/induzido quimicamente , Anemia/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Contagem de Células Sanguíneas , Estudos Transversais , Etiópia/epidemiologia , Feminino , Doenças Hematológicas/epidemiologia , Humanos , Leucopenia/induzido quimicamente , Leucopenia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Adulto Jovem
16.
Int J Surg ; 62: 34-43, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30641155

RESUMO

BACKGROUND: Gastric cancer, as one of the increasingly common malignancies, has experienced high morbidity throughout many countries at present. Currently, chemotherapy regimen with more efficacy and safety for advanced gastric cancer (AGC) is needed. We aimed to assess the clinical efficacy and safety of S-1 combined with paclitaxel (PTX) for AGC by performing a systematic review and meta-analysis of the published studies. METHOD: All published randomized controlled trials (RCTs) of S-1 combined with PTX for AGC were searched. Studies that included patients with locally advanced or metastases' gastric cancers were included. We searched the databases included Cochrane Library of Clinical Comparative Trials, MEDLINE, Embase, American Society of Clinical Oncology meeting abstracts and China National Knowledge Internet (CNKI) from 2000 to 2018. We searched the database up to January 2018. The first endpoint was overall survival (OS). Other endpoints were progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Safety analyses were also performed. RESULTS: A total of 7 trials (including 1407 patients, 711 patients in intervention group and 696 patients in control group) were included in the present analysis. S-1 combined with PTX significantly improved the OS [HR = 0.78, 95% CI: 0.60-0.97, P = 0.000],PFS [HR = 0.70, 95% CI: 0.55-0.85, P = 0.000], ORR [RR = 1.30, 95%CI: 1.05-1.60, P = 0.017] and DCR [RR = 1.15, 95%CI: 1.04-1.27, P = 0.008] of patients with AGC. The grade 3 or 4 haematological and non-hematologic toxicities were anemia [RR = 1.71, 95% CI: 1.04-2.79, P = 0.03], neutropenia [RR = 1.65, 95% CI: 1.32-2.06, P < 0.0001] and anorexia [RR = 1.66, 95% CI: 1.05-2.64, P = 0.03] respectively. CONCLUSION: S-1 combined with PTX may be a good choice for patients with AGC. S-1 plus PTX experienced more efficacy and safety when compared with S-1 alone or S-1 plus other drugs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Combinação de Medicamentos , Doenças Hematológicas/induzido quimicamente , Humanos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Tegafur/administração & dosagem , Tegafur/efeitos adversos
17.
Int J Clin Oncol ; 24(5): 508-515, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30604155

RESUMO

BACKGROUND: Dose modification of chemotherapy for metastatic colorectal cancer (MCRC) is often needed, especially in second-line and later-line treatments due to adverse events of previous treatment and poor patient condition. No study has focused on ramucirumab plus modified dose of FOLFIRI for MCRC, and whether low relative dose intensity (RDI) affects treatment efficacy has not been clarified. METHODS: MCRC patients who received ramucirumab plus FOLFIRI, which consisted of 150 mg/m2 of irinotecan, at six institutions were retrospectively analyzed. RESULTS: A total of 43 patients were assessed. Median age was 63 years, and 22 patients (51%) were women. Twenty-six patients (60%) were given ramucirumab plus FOLFIRI as second-line therapy, and 17 (40%) as third or later-line. The median relative dose intensity (RDI) of irinotecan was 60.6%, which is lower than that in the pivotal phase 3 study (RAISE), and other agents showed the same trend. Median progression-free survival was 4.8 [95% confidence interval (CI) 3.2-5.7] months for all patients, 5.4 (95% CI 3.5-7.2) months for second-line patients, and 2.8 (95% CI 1.6-5.8) months for third or later-line patients. Median overall survival was 17.3 (95% CI 11.5-22.4) months for all patients. Patients with irinotecan RDI less than 60% showed similar treatment efficacy. Hematological toxicities of grade 3 or worse were observed in 21 patients, but all were manageable. CONCLUSION: Low RDI did not compromise the treatment efficacy of ramucirumab plus modified FOLFIRI for MCRC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Doenças Hematológicas/induzido quimicamente , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
18.
J Oncol Pharm Pract ; 25(7): 1749-1753, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30293481

RESUMO

Ovarian cancer is the second most common and the most lethal gynecological malignancy in the western world. Unfortunately, there are lack of methods for early screening and diagnosis of the disease. Because of this, most of the cases are diagnosed at an advanced stage and have poor prognosis. The standard treatment of ovarian cancer is maximal cytoreductive surgical debulking followed by platinum-based chemotherapy. There are new molecular agents available for maintenance therapy of ovarian cancer including anti-angiogenic therapies, poly adenosine diphosphate ribose polymerase inhibitors, inhibitors of growth factor signaling, or folate receptor inhibitors, as well as several immunotherapeutic approaches. Niraparib is a poly adenosine diphosphate ribose polymerase inhibitor that has shown to be clinically effective as maintenance therapy in patients with platinum sensitive, recurrent ovarian cancer. Studies have shown the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of presence or absence of BRCA gene mutations or homologous recombination deficiency status. Studies have shown that treatment-emergent Grade 3 or Grade 4 hematological events were observed in patients receiving niraparib including thrombocytopenia (33.8%), anemia (25.3%) and neutropenia (19.6%). Most of the hematological laboratory abnormalities occurred within the first three treatment cycles. After dose adjustment, the incidence of hematological abnormalities was infrequent beyond cycle 3. We are reporting two cases of Grade III/IV neutropenia and thrombocytopenia in patients treated with niraparib in our institution. Unfortunately, one of the patients succumbed to septic shock secondary to right lower lobe pneumonia while severely neutropenic. The second patient's blood counts improved after discontinuing the medication and with supportive transfusions during the hospitalization.


Assuntos
Indazóis/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Piperidinas/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Idoso de 80 Anos ou mais , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Indazóis/efeitos adversos , Pessoa de Meia-Idade , Mutação , Piperidinas/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos
19.
Am J Hematol ; 94(1): 46-54, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30290003

RESUMO

SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor (TKI) use and management patterns in patients with chronic phase-chronic myeloid leukemia in the US and Europe in routine clinical practice. Herein we describe interruptions, discontinuations and switching of TKI therapy during the initial 2 years of treatment among 1121 patients prospectively enrolled between October 1, 2010 and March 7, 2017. Patient characteristics were broadly similar between the imatinib (n = 370), dasatinib (n = 376), and nilotinib (n = 375) cohorts. Treatment interruptions occurred in 16.4% (year 1) and 4.0% (year 2) of patients, mainly attributed to hematologic intolerances. Treatment discontinuations occurred in 21.8% (year 1) and 10.2% (year 2) of patients, with the highest rate within the first 3 months for intolerance. Switching of TKI was seen in 17.8% (year 1) and 9.5% (year 2) of patients. Significant associations were found between TKI switching and female gender (year 1), age ≥65 years at diagnosis (year 2) and treatment with imatinib (year 2). Intolerance was the most common reason given for patients discontinuing and for switching TKI therapy; however resistance was also cited. Lack of response monitoring in routine clinical practice may have resulted in lower identification of resistance in this dataset. Data from SIMPLICITY suggest that, in routine clinical practice, intolerance and resistance to TKIs influence decisions to change treatment. Changes in TKI therapy are frequent, with nearly a third of patients discontinuing their first-line TKI.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Dasatinibe/administração & dosagem , Dasatinibe/efeitos adversos , Dasatinibe/uso terapêutico , Gerenciamento Clínico , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Substituição de Medicamentos , Europa (Continente) , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/uso terapêutico , Masculino , Doenças Musculoesqueléticas/induzido quimicamente , Estudos Prospectivos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Doenças Respiratórias/induzido quimicamente , Estados Unidos
20.
J Oncol Pharm Pract ; 25(1): 44-51, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28825377

RESUMO

BACKGROUND: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early non-small cell lung cancer. However, few validated alternatives exist when cisplatin is not indicated or tolerated. Carboplatin is frequently used in this setting. We evaluated the 5-year overall survival, progression-free survival and toxicity in patients treated for stage IB to IIIB resected non-small cell lung cancer receiving adjuvant carboplatin-based chemotherapy compared to cisplatin in association with vinorelbine. METHODS: Single-center retrospective study of patients having received adjuvant chemotherapy between January 2004 and December 2013 at the oncology clinic at Institut Universitaire de Cardiologie et de Pneumologie de Québec (Canada). Three sub-groups, cisplatin/vinorelbine, carboplatin/vinorelbine and the substitution of cisplatin/vinorelbine for carboplatin/vinorelbine (cisplatin/vinorelbine/carboplatin/vinorelbine), were studied during treatment. RESULTS: One hundred twenty-seven patients were included in this study. The median PFS was not significantly different, with 50.4 months for cisplatin/vinorelbine, 57.3 months for cisplatin/vinorelbine/carboplatin/vinorelbine and not yet achieved for the carboplatin/vinorelbine group ( p = 0.80). Overall survival also did not differ significantly between the three groups. The 5-year overall survival rates were 66% in cisplatin/vinorelbine group, 55% in carboplatin/vinorelbine group and 70% in cisplatin/vinorelbine/carboplatin/vinorelbine group ( p = 0, 95). No differences were noted between groups concerning high-grade hematologic toxicity. CONCLUSIONS: Although the effectiveness and hematologic toxicity are comparable between cisplat in and carboplatin in the adjuvant treatment of resected non-small cell lung cancer, the results obtained corroborate the practice used at our oncology clinic. Nevertheless, more prospective studies would be needed to confirm these results.


Assuntos
Carboplatina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino , Doenças Hematológicas , Neoplasias Pulmonares/tratamento farmacológico , Vinorelbina , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Canadá , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/prevenção & controle , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Vinorelbina/administração & dosagem , Vinorelbina/efeitos adversos
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