Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.208
Filtrar
1.
Ann Hematol ; 98(9): 2121-2129, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31240469

RESUMO

We retrospectively analyzed 70 patients with classical Hodgkin lymphoma (cHL) who were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiotherapy to assess the influence of the soluble interleukin-2 receptor (sIL-2R) level at diagnosis on the clinical outcome. Receiver operating characteristic analyses determined that the optimal cutoff value of the sIL-2R level for progression-free survival (PFS) was 2490 U/mL. Using this cutoff value, patients were classified into low (n = 46) and high (n = 24) sIL-2R groups. The patients in the high sIL-2R group exhibited a significantly inferior PFS (44.1% vs. 90.4% at 5 years, P < 0.001) and overall survival (OS) (67.6% vs. 94.7% at 5 years, P = 0.001) compared with those in the low sIL-2R group. Multivariate analysis showed that a high sIL-2R level was an independent prognostic factor for PFS after adjusting for stage, white blood cell, hemoglobin, and B symptoms, and also OS after adjusting for age and stage (hazard ratio (HR) 6.49, P < 0.001 and HR 5.98, P = 0.009, respectively). In patients with advanced-stage cHL, a high sIL-2R level predicted 5-year PFS even after adjustment for international prognostic score > 4 (HR 6.00, P = 0.007). These results demonstrate that the sIL-2R level can be a useful prognostic factor in patients with cHL treated with ABVD with or without radiotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia , Doença de Hodgkin , Proteínas de Neoplasias/sangue , Receptores de Interleucina-2/sangue , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Vimblastina/administração & dosagem
2.
Rinsho Shinkeigaku ; 59(6): 349-355, 2019 Jun 22.
Artigo em Japonês | MEDLINE | ID: mdl-31142709

RESUMO

The case of a 17-year-old man with Hodgkin's lymphoma who presented with paraneoplastic sensory neuropathy is presented. The patient visited our hospital because of acute progression of dysesthesiae in the bilateral face and extremities. He also developed an ataxic gait due to decreased deep sensation. Post-contrast T1-weighted MRI showed enhancement of both trigeminal nerves and the cauda equina. Cerebrospinal fluid examination was unremarkable. Intravenous immunoglobulin therapy and subsequent steroid pulse therapy did not improve his symptoms. Laboratory data showed an elevated serum soluble interleukin-2 receptor level. His chest X-ray and CT showed enlarged lymph nodes in the mediastinum, and the histopathologic examination of a lymph node biopsy specimen showed classical Hodgkin's lymphoma. He was treated with chemotherapy. His symptoms of neuropathy improved promptly while the lymphoma was being successfully treated, and he was able to walk with a cane. The present case was characterized by paraneoplastic sensory neuropathy as the initial clinical feature in association with Hodgkin's lymphoma. It is necessary to consider a paraneoplastic neurological syndrome even in a young patient with acute/subacute sensory neuropathy. Paraneoplastic sensory neuropathy associated with Hodgkin's lymphoma could be expected to improve with oncotherapy, and examination of the malignancy and early treatment are important.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/complicações , Doença de Hodgkin/tratamento farmacológico , Neoplasias do Mediastino/complicações , Neoplasias do Mediastino/tratamento farmacológico , Polineuropatia Paraneoplásica/tratamento farmacológico , Polineuropatia Paraneoplásica/etiologia , Parestesia/tratamento farmacológico , Parestesia/etiologia , Doença Aguda , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ataxia/tratamento farmacológico , Ataxia/etiologia , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Doença de Hodgkin/diagnóstico , Humanos , Imagem por Ressonância Magnética , Masculino , Neoplasias do Mediastino/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vimblastina/administração & dosagem
4.
J Pept Sci ; 24(10): e3118, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30084214

RESUMO

Some Vinca alkaloids (eg, vinblastine, vincristine) have been widely used as antitumor drugs for a long time. Unfortunately, vindoline, a main alkaloid component of Catharanthus roseus (L.) G. Don, itself, has no antitumor activity. In our novel research program, we have prepared and identified new vindoline derivatives with moderate cytostatic activity. Here, we describe the effect of conjugation of vindoline derivative with oligoarginine (tetra-, hexa-, or octapeptides) cell-penetrating peptides on the cytostatic activity in vitro and in vivo. Br-Vindoline-(l)-Trp-OH attached to the N-terminus of octaarginine was the most effective compound in vitro on HL-60 cell line. Analysis of the in vitro activity of two isomer conjugates (Br-vindoline-(l)-Trp-Arg8 and Br-vindoline-(d)-Trp-Arg8 suggests the covalent attachment of the vindoline derivatives to octaarginine increased the antitumor activity significantly against P388 and C26 tumour cells in vitro. The cytostatic effect was dependent on the presence and configuration of Trp in the conjugate as well as on the cell line studied. The configuration of Trp notably influenced the activity on C26 and P388 cells: conjugate with (l)-Trp was more active than conjugate with the (d)-isomer. In contrast, conjugates had very similar effect on both the HL-60 and MDA-MB-231 cells. In preliminary experiments, conjugate Br-vindoline-(l)-Trp-Arg8 exhibited some inhibitory effect on the tumor growth in P388 mouse leukemia tumor-bearing mice. Our results indicate that the conjugation of modified vindoline could result in an effective compound even with in vivo antitumor activity.


Assuntos
Antineoplásicos/administração & dosagem , Peptídeos Penetradores de Células/química , Leucemia/tratamento farmacológico , Oligopeptídeos/química , Vimblastina/análogos & derivados , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HL-60 , Humanos , Camundongos , Estrutura Molecular , Vimblastina/administração & dosagem , Vimblastina/química , Vimblastina/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
BMJ Case Rep ; 20182018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30061135

RESUMO

Hodgkin's lymphoma (HL) is a type of cancer originating in the lymph nodes. The preferred therapy for advanced HL is a combination of chemotherapies including doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). ABVD has been standard therapy for advanced HL. It is generally considered as safe and rarely has been reported to cause acute liver failure. We present a case of 79-year-old woman with HL, who developed acute liver failure secondary to first cycle of ABVD chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença de Hodgkin/tratamento farmacológico , Imunoconjugados/uso terapêutico , Síncope/induzido quimicamente , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/complicações , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos
6.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(7): 754-759, 2018 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-30124211

RESUMO

OBJECTIVE: To investigate the clinical efficacy and toxicities for the NAPD regimen (vinorelbine, cytarabine, cisplatin, and dexamethasone) in the treatment of recurrent refractory diffuse large B-cell lymphoma.
 Methods: A total of 30 patients identified with recurrent refractory diffuse large B-cell lymphoma were enrolled in this retrospective study. The curative efficacy of NAPD regimen was evaluated after 2 consecutive cycles. The toxicities and adverse reaction were evaluated after 1 cycle. The objective response rate (ORR), overall survival (OS), progress free survival (PFS), and the rates of 1, 2, and 4-year OS and PFS were analyzed. The prognosis was evaluated with univariate analysis.
 Results: The ORR was 56.7% and clinical benefit rate (CBR) was 83.3% after 2 cycles. Five patients achieved complete remission, 12 achieved partial remission, and 8 achieved stable disease. The median OS was 22 (1.5-140) months. The 1, 2, and 4-year OS rates were 59.1%, 48.2%, and 40.2%, respectively. The median PFS was 14 (1.5-140) months. The 1, 2 and 4-year PFS rates were 56.3%, 42.2%, and 31.7%, respectively. The main adverse reaction was myelosuppression. Three patients suffered from grade III-IV leukopenia and 1 thrombocytopenia. Grade I-II gastrointestinal toxicity was 20%. No heart, liver, and kidney damages at grade III-IV were observed.
 Conclusion: The NAPD regimen is effective and its toxicity is well tolerated for the treatment of recurrent refractory diffuse large B-cell lymphoma. It is a salvage chemotherapy regimen worth to be verified.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Humanos , Quimioterapia de Indução , Linfoma Difuso de Grandes Células B/mortalidade , Recidiva Local de Neoplasia/mortalidade , Estudos Retrospectivos , Terapia de Salvação/métodos , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina
7.
Cochrane Database Syst Rev ; 7: CD012838, 2018 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-30036453

RESUMO

BACKGROUND: The use of systemic immunotherapy targets is emerging as an important treatment option for metastatic urothelial carcinoma, particularly for patients who cannot tolerate or who fail cisplatin-based chemotherapy. One such target is the inhibition of the checkpoint protein programmed cell death-1 (PD-1) receptor and its ligand (PD-L1) by monoclonal antibodies. OBJECTIVES: To assess the effects of pembrolizumab monotherapy versus chemotherapy for treatment of advanced urothelial carcinoma with disease progression during or following platinum-containing chemotherapy. SEARCH METHODS: We performed a Cochrane Rapid Review, limiting our search to published studies in the English language. We searched databases of the medical literature, including the Cochrane Central Register of Controlled Trials and MEDLINE, as well as trial registries including ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). Our search extended from January 2000 to June 2018. SELECTION CRITERIA: We included randomised controlled trials except cross-over trials and cluster randomised trials. We excluded all other study designs. Participants included had locally advanced or metastatic urothelial carcinoma of the bladder, with disease progression during or following platinum-containing chemotherapy (synonymous with second-/third-/fourth-line therapy). This review focused on pembrolizumab (synonyms: MK-3475, lambrolizumab, Keytruda). DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included study. The certainty of evidence was rated according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We identified one randomised controlled trial that included 542 participants, which compared the use of pembrolizumab monotherapy versus chemotherapy for the treatment of advanced urothelial carcinoma with disease progression during or following platinum-containing chemotherapy. Results were reported after a median follow-up of 14.1 months (range 9.9 to 22.1 months).Primary outcomesPembrolizumab probably reduces the risk of death from any cause (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59 to 0.90; moderate certainty evidence). This corresponds to 115 fewer deaths (191 fewer to 38 fewer) per 1000 participants with pembrolizumab at 12 months. We downgraded the certainty of evidence one level for imprecision.Pembrolizumab may slightly improve quality of life (change from baseline to week 15 assessed with the Core Quality of Life Questionnaire; higher value reflects better quality of life; scale 0 to 100) with a mean difference (MD) of 9.05, 95% CI 4.61 to 13.50; low certainty evidence). We downgraded the certainty of evidence two levels for study limitations and imprecision.Secondary outcomesPembrolizumab may have little or no effect on disease progression (HR 0.98, 95% CI 0.81 to 1.19; low certainty evidence). This corresponds to three fewer patients (42 fewer to 24 more) whose disease progressed per 1000 participants at 12 months. We downgraded the certainty of evidence two levels for study limitations and imprecision.Pembrolizumab probably improves treatment response (based on complete or partial radiologic response) with a risk ratio (RR) of 1.85, 95% CI 1.24 to 2.77; moderate certainty evidence). This corresponds to 97 more respondents (27 more to 202 more) per 1000 participants with pembrolizumab. We downgraded the certainty of evidence one level for imprecision.Pembrolizumab may have little or no effect on treatment-related mortality (RR 0.96, 95% CI 0.24 to 3.79; low certainty evidence). This corresponds to one fewer (12 fewer to 44 more) treatment-related deaths per 1000 participants with pembrolizumab. We downgraded the certainty of evidence two levels for study limitations and imprecision.Pembrolizumab may have little or no effect on discontinuations due to adverse events (RR 0.66, 95% CI 0.39 to 1.10). This corresponds to 54 fewer discontinuations per 1000 participants (95% CI 79 fewer to 7 more). We downgraded the certainty of evidence for study limitations and imprecision.Pembrolizumab may reduce serious adverse events (RR 0.83, 95 CI 0.72 to 0.97; low certainty evidence). This corresponds to 107 fewer serious averse events per 1000 participants (95% CI 19 fewer to 176 fewer). We downgraded two levels for study limitations and imprecision. AUTHORS' CONCLUSIONS: The use of pembrolizumab in men with advanced urothelial carcinoma with disease progression during or following platinum-containing chemotherapy probably improves overall survival when compared with chemotherapy alone. At 12 months follow-up about 70% of those in the chemotherapy group had died, compared with 59% of those treated with pembrolizumab. We are very uncertain about the effects of pembolizumab on quality of life. Pembolizumab may also improve treatment response rates, and reduce the risk of serious adverse events, but may make little or no difference to discontinuations of treatment due to adverse events. These conclusions are based on a single trial that was sponsored by the producer of pembrolizumab.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma/patologia , Progressão da Doença , Docetaxel , Humanos , Paclitaxel/administração & dosagem , Qualidade de Vida , Taxoides/administração & dosagem , Neoplasias da Bexiga Urinária/patologia , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados
9.
Anticancer Res ; 38(6): 3689-3697, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29848729

RESUMO

AIM: To explore the feasibility and activity of oral metronomic vinorelbine patients with advanced NSCLC not eligible to standard chemotherapy because of old age (≥70 years), and/or poor Eastern Cooperative Oncology Group performance status (≥2), and/or extensive brain or bone disease, and/or active comorbidities (≥2) requiring for pharmacological treatment. PATIENTS AND METHODS: In a prospective phase II not randomized study, patients with stage IV NSCLC unfit to chemotherapy were treated with oral metronomic vinorelbine at 30 mg fixed dose three times a week until disease progression. RESULTS: Fifty patients were treated, 19 (38%) in the first-line setting. Five patients (11%) experienced a grade 3 toxicity; no grade 4 toxicity occurred. Overall disease control rate was 32%, 44% and 26% in first and subsequent lines, respectively (p=0.39). Median OS and PFS were 7.3 months (95% confidence interval [CI]=4.7-10.0) and 2.7 months (95%CI=2.0-3.4), respectively. CONCLUSION: These data support the activity and safety of metronomic vinorelbine in a relevant proportion of patients usually excluded from any specific treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Administração Metronômica , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Astenia/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/patologia , Constipação Intestinal/induzido quimicamente , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Estudos Prospectivos , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Vinorelbina
10.
Medicine (Baltimore) ; 97(19): e0607, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29742695

RESUMO

RATIONALE: In the thorax, Hodgkin lymphoma (HL) most frequently involves the anterior mediastinal and paratracheal regions and tends to spread to contiguous nodal groups. Enlarged lymph nodes typically have homogeneous soft tissue attenuation similar to that of muscle tissue on computed tomography (CT). PATIENT CONCERNS: A contrast-enhanced CT examination of a 19-year-old man with right-sided chest pain showed an intense, heterogeneously enhancing mass with organization of serpentine and dilated blood vessels in the right anterior mediastinum that had invaded the upper lobe of the right lung. DIAGNOSES: Following a wedge resection, histopathological examination showed Reed-Sternberg cells that were positive for CD-15 and CD-30, which is typical of HL. INTERVENTIONS: The patient was started treatment with 6 cycles of doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD) regimen. OUTCOMES: After chemotherapy, the patient had shown a partial response to the treatment. LESSONS: This presentation of HL as an extremely hypervascular anterior mediastinal mass on CT imaging has not been previously reported in the literature. This case suggests that HL should be included in the differential diagnosis of a hypervascular anterior mediastinal mass, especially if the patient is a young adult.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dissecação/métodos , Doença de Hodgkin , Neoplasias do Mediastino , Mediastino , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Diagnóstico Diferencial , Doxorrubicina/administração & dosagem , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/patologia , Doença de Hodgkin/fisiopatologia , Doença de Hodgkin/terapia , Humanos , Pulmão/diagnóstico por imagem , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/fisiopatologia , Neoplasias do Mediastino/terapia , Mediastino/irrigação sanguínea , Mediastino/diagnóstico por imagem , Células de Reed-Sternberg/patologia , Fluxo Sanguíneo Regional , Tomografia Computadorizada por Raios X/métodos , Vimblastina/administração & dosagem , Adulto Jovem
11.
Curr Drug Deliv ; 15(8): 1135-1145, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29629662

RESUMO

BACKGROUND: Vinorelbine bitartrate (VRL), a semi synthetic vinca alkaloid approved for breast cancer, has been proven to be beneficial as first line and subsequent therapies. However, its hydrophilic and thermo labile nature provides hindrance to oral clinical translation. OBJECTIVES: The current work focused on the application of DOE a modern statistical optimization tool for the development and optimization of a solid lipid nanoparticle (SLN) formulation that can encapsulate hydrophilic and thermolabile Vinorelbine bitartrate (VRL) to a maximum extent without compromising integrity and anticancer activity of the drug. METHODS: SLNs were prepared by solvent diffusion technique employing Taguchi orthogonal array design with optimized formulation and process variables. The emulsifying nature and low melting point of glyceryl mono-oleate (GMO) were exploited to enhance entrapment and minimizing temperature associated degradation, respectively. Moreover, two types of surfactants, Vitamin E TPGS (TPGS) and Poloxamer-188 were utilized to obtain TPGS-VRL-SLNs and PL-VRL-SLNs, respectively. The SLNs were characterized for various physicochemical properties, in-vitro drug release kinetics and anticancer activity by MTT assay on MCF-7 cancer cell lines. RESULTS: The SLNs were found to be spherical in shape with entrapment efficiency (EE) up to 58 %. Invitro release studies showed biphasic release pattern following Korsemeyer peppas model with fickian release kinetics. Results of MTT assay revealed that TPGS-VRL-SLNs and PL-VRL-SLNs were 39.5 and 18.5 fold more effective, respectively, compared to the pristine VRL. CONCLUSION: DOE approach was successfully applied for the development of VRL-SLNs. Enhanced entrapment and anticancer efficacy of TPGS-VRL-SLN can be attributed to emulsifying nature of GMO and inherent cytotoxic nature of TPGS, respectively, which synergizes with VRL. Therefore, TPGS associated SLNs may be potential carrier in cancer chemotherapeutics.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , Vimblastina/análogos & derivados , Vitamina E/administração & dosagem , Vitaminas/administração & dosagem , Antineoplásicos Fitogênicos/química , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Emulsões , Glicerídeos/administração & dosagem , Glicerídeos/química , Humanos , Células MCF-7 , Nanopartículas/química , Vimblastina/administração & dosagem , Vimblastina/química , Vinorelbina , Vitamina E/química , Vitaminas/química
12.
Surg Today ; 48(7): 687-694, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29502152

RESUMO

PURPOSE: We reported previously a phase II study of adjuvant chemotherapy consisting of four cycles of vinorelbine (25 mg/m2) and cisplatin (40 mg/m2), given on days 1 and 8, every 4 weeks, to Japanese patients with completely resected stage II or III non-small cell lung cancer (NSCLC; UMIN 000005055). However, the follow-up was too short for us to evaluate a definitive 5-year overall survival rate and after-effects. METHODS: Between December 2006 and January 2011, 60 patients were enrolled in this study. We analyzed relapse-free and overall survival, long-lasting adverse effects, the influence of treatment on recurrent tumors, and the development of a second primary cancer, in relation with the regimen. RESULTS: After a median follow-up period of 95.8 months, the 5-year relapse-free and overall survival rates were 51.7 and 76.7%, respectively. Neuralgia developed in one patient and this was the only case of a long-lasting adverse effect. Recurrence developed in 31 patients, 29 of whom received intensive treatment. Although 16 s (or more) primary neoplasms developed among 13 patients, these were common carcinomas in Japan and did not include sarcoma or hematologic malignancies. CONCLUSION: Adjuvant vinorelbine and cisplatin chemotherapy showed encouraging relapse-free and overall survival rates, and long-term safety in Japanese patients with resected NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Pneumonectomia , Vimblastina/análogos & derivados , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vimblastina/administração & dosagem , Vinorelbina
13.
Yakugaku Zasshi ; 138(3): 437-442, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-29503435

RESUMO

 Adjuvant cisplatin-vinorelbine chemotherapy has been shown to be effective in patients with completely resected non-small cell lung cancer (NSCLC) in several Phase III trials, but not yet in the Japanese population. Pharmacists are expected to assist patients with completion of adjuvant chemotherapy. The aim of this retrospective study was to evaluate the compliance with and safety of adjuvant cisplatin-vinorelbine chemotherapy in Japanese patients and to evaluate the contribution of pharmacists to completion of treatment. Thirty-four patients with NSCLC who received adjuvant cisplatin-vinorelbine chemotherapy at Kyorin University Hospital between January 2006 and June 2015 were reviewed. The treatment schedule comprised cisplatin 80 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8 every 3 weeks. Four 3-week cycles were planned. A pharmacist provided guidance to all patients and monitored them for adverse effects thereafter. The pharmacist intervened with advice to doctors as necessary. The 4 cycles were administered in 67.6% of cases. There were no treatment-related deaths. The main grade 3 or 4 toxicities were neutropenia (76.5%) and anorexia (38.2%). The most common reason for discontinuation and dose reduction was anorexia. There were 56 instances of pharmacist intervention. In total, 96.4% of the pharmacist interventions were implemented by doctors, which included administration of an antiemetic on 15 occasions and hot fomentation for prevention of vasculitis on 7 occasions. Adjuvant cisplatin-vinorelbine chemotherapy was tolerated by most patients but was discontinued because of adverse events in some. Pharmacist intervention aids completion of planned chemotherapy and management of treatment-related adverse events.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimioterapia Adjuvante , Neoplasias Pulmonares/terapia , Cooperação do Paciente , Farmacêuticos , Papel Profissional , Anorexia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Humanos , Neutropenia/induzido quimicamente , Pneumonectomia , Estudos Retrospectivos , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , Vinorelbina
14.
Bull Cancer ; 105(2): 155-161, 2018 Feb.
Artigo em Francês | MEDLINE | ID: mdl-29395041

RESUMO

INTRODUCTION: Our home care unit (HCU) developed the administration of IV chemotherapy at home for some pediatric oncologic patients. METHODS: We conducted a retrospective monocentric analysis, leading to identify patients with at least one sequence of chemotherapy at home in 2015. RESULTS: Two hundred and forty four sequences of home chemotherapy have been administered in 2015. We identified two situations for home IV chemotherapy. Pediatric oncologist of day hospital prescribes the sequence. The chemotherapy is delivered at hospital for the first day. HCU takes over for the next days at home. For a sequence replacing a conventional hospitalization, the attending physician examines the patient, and confirm the clinical validation. The pediatric oncologist of HCU checks lab exams, and prescribes the chemotherapy. For both situations, IV chemotherapy is prepared by our hospital pharmacy, delivers at home or at day hospital, and HCU team manages home material and organizes hospitalization. CONCLUSIONS: This kind of organization allows setting up home IV CT for more and more patients. It allows to limit daily hospitalization for some patients living far from the hospital, and whose therapies lead to several hospitalizations.


Assuntos
Antineoplásicos/administração & dosagem , Serviços Hospitalares de Assistência Domiciliar/organização & administração , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Criança , Citarabina/administração & dosagem , Neoplasias Oculares/tratamento farmacológico , Feminino , Glioma/tratamento farmacológico , Acesso aos Serviços de Saúde , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Injeções Intravenosas/estatística & dados numéricos , Masculino , Enfermagem Oncológica , Enfermagem Pediátrica , Pediatras , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Fatores de Tempo , Vimblastina/administração & dosagem
15.
Ann Hematol ; 97(7): 1229-1240, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29484455

RESUMO

Hodgkin lymphoma (HL) patients failing after high dose chemotherapy (HDC) and auto-SCT have a poor outcome. Some patients may still benefit from further treatments. From 1996 to 2016, 137 HL patients (39.5%) out of 347 transplanted experienced post auto-SCT failure. Males/female 61%:39%, median age at auto-SCT 23.4 years and median follow-up 55.6 months (9-153). Type of failure was progressive (46%), relapsed (35%) or persistent disease/refractory disease (19%). Median overall survival (OS) from the time of failure is 20 months; 35 patients (25.5%) are alive. One hundred and four patients received treatment; the response rate was 45%; complete remission in 41 (30%) and partial remission in 21 (15%) patients. 1st interventions post auto-SCT were chemotherapy (39%), radiation therapy (35%) or best supportive care (24%). Twenty-seven patients with 2nd-SCT (allogeneic (15), auto-SCT (2)) and/or brentuximab (18 patients) had superior OS (50.6 months) vs other treatments (22.5 months, P value 0.037). COX regression multivariate analysis identified post auto-SCT treatment failure before 12 months (hazard ratio (HR) 3.37, CI 1.7-6.6, P value < 0.001), presence of B symptoms (HR 2.55, CI 1.4-4.6, P value 0.002), stages III-IV (HR 2.7, CI 1.5-4.9, P value 0.001), albumin < 4 g/dl (HR 1.76, CI 1.1-2.9, P value 0.027) and tumor > 5 cm (HR 1.1.9, CI 1.13-3.25, P value 0.015) as significant risk factors; P value < 0.001. KM OS with 0-1 factor (148.6 months): 2 factors (23.6 months) and 3-5 factors (9.4 months) (P value < 0.001). OS was 63%:25%:7% respectively with 0-1:2:3-5 factors respectively (P value < 0.001). Despite high-risk factors, 2nd-SCT/brentuximab use post HDC auto-SCT failure may result in durable survival.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/mortalidade , Adolescente , Adulto , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Carmustina/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Citarabina/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/administração & dosagem , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Doença de Hodgkin/terapia , Humanos , Imunoconjugados/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Melfalan/administração & dosagem , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Terapia de Salvação , Condicionamento Pré-Transplante , Transplante Autólogo , Vimblastina/administração & dosagem , Adulto Jovem
16.
PLoS One ; 13(1): e0191766, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29364966

RESUMO

Emerging drug-resistance and drug-associated toxicities are two major factors limiting successful cancer therapy. Combinations of chemotherapeutic drugs have been used in the clinic to improve patient outcome. However, cancer cells can acquire resistance to drugs, alone or in combination. Resistant tumors can also exhibit cross-resistance to other chemotherapeutic agents, resulting in sub-optimal treatment and/or treatment failure. Therefore, developing novel oncology drugs that induce no or little acquired resistance and with a favorable safety profile is essential. We show here that combining COTI-2, a novel clinical stage agent, with multiple chemotherapeutic and targeted agents enhances the activity of these drugs in vitro and in vivo. Importantly, no overt toxicity was observed in the combination treatment groups in vivo. Furthermore, unlike the tested chemotherapeutic drugs, cancer cells did not develop resistance to COTI-2. Finally, some chemo-resistant tumor cell lines only showed mild cross-resistance to COTI-2 while most remained sensitive to it.


Assuntos
Aminoquinolinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tiossemicarbazonas/uso terapêutico , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/patologia , Camundongos , Paclitaxel/administração & dosagem , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Jpn J Clin Oncol ; 48(3): 242-247, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29315394

RESUMO

Background: The combination of lapatinib and oral vinorelbine for HER2 positive metastatic breast cancer (MBC) is convenient but with uncertain toxicity profiles. A Phase I/II study was designed to understand the tolerability and efficacy of this combination treatment. Method: Female MBC patients with HER2 positive were eligible. Lapatinib was given once daily and oral vinorelbine was given on Days 1 and 8 of a 21-day cycle. A 3 + 3 standard dose-escalation rule was applied in the Phase I study. The primary endpoint of the Phase II study was PFS. In the Phase II part, because no DLT was observed in the first 20 patients, vinorelbine dose-escalation was permitted if no significant toxicities after the first cycle was observed. Result: From June 2009 to February 2013, 46 patients were enrolled in Phase I (n = 15) and II (n = 31) studies. Median age was 52.8 (range 34.3-84.0); 28 (60.9%) patients were ER positive. In the Phase I study, two patients had DLTs (neutropenia (n = 2), diarrhea (n = 1)). The MTD was determined at lapatinib 1000 mg plus oral vinorelbine 50 mg/m2. In the Phase II study, 11 patients safely had vinorelbine escalated to 60 mg/m2 on cycle 2. The median PFS was 5.6 months (95% CI 5.2-5.9); 6 (19.4%) patients had PR; the clinical benefit rate was 38.7%. Six patients had disease control over 2 years. Conclusion: Lapatinib 1000 mg and oral vinorelbine 50 mg/m2 were tolerable with manageable toxicities. Escalation to vinorelbine 60 mg/m2 is feasible if no significant toxicities after the first cycle. Clinical efficacy was demonstrated with long-term responders observed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Quinazolinas/uso terapêutico , Vimblastina/análogos & derivados , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Demografia , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Lapatinib , Pessoa de Meia-Idade , Metástase Neoplásica , Quinazolinas/efeitos adversos , Receptor ErbB-2/metabolismo , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Vinorelbina
18.
N Engl J Med ; 378(4): 331-344, 2018 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-29224502

RESUMO

BACKGROUND: Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has been approved for relapsed and refractory Hodgkin's lymphoma. METHODS: We conducted an open-label, multicenter, randomized phase 3 trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma, in which 664 were assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) and 670 were assigned to receive doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The primary end point was modified progression-free survival (the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) as adjudicated by an independent review committee. The key secondary end point was overall survival. RESULTS: At a median follow-up of 24.6 months, 2-year modified progression-free survival rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval [CI], 78.8 to 85.0) and 77.2% (95% CI, 73.7 to 80.4), respectively, a difference of 4.9 percentage points (hazard ratio for an event of progression, death, or modified progression, 0.77; 95% CI, 0.60 to 0.98; P=0.04). There were 28 deaths with A+AVD and 39 with ABVD (hazard ratio for interim overall survival, 0.73 [95% CI, 0.45 to 1.18]; P=0.20) [corrected]. All secondary efficacy end points trended in favor of A+AVD. Neutropenia occurred in 58% of the patients receiving A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor than among those who did not (11% vs. 21%). Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43% of patients in the ABVD group; 67% of patients in the A+AVD group who had peripheral neuropathy had resolution or improvement at the last follow-up visit. Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients receiving A+AVD and in 3% of those receiving ABVD. Among the deaths that occurred during treatment, 7 of 9 in the A+AVD group were associated with neutropenia and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity. CONCLUSIONS: A+AVD had superior efficacy to ABVD in the treatment of patients with advanced-stage Hodgkin's lymphoma, with a 4.9 percentage-point lower combined risk of progression, death, or noncomplete response and use of subsequent anticancer therapy at 2 years. (Funded by Millennium Pharmaceuticals and Seattle Genetics; ECHELON-1 ClinicalTrials.gov number, NCT01712490 ; EudraCT number, 2011-005450-60 .).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Imunoconjugados/administração & dosagem , Fatores Imunológicos/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Doença de Hodgkin/mortalidade , Humanos , Imunoconjugados/efeitos adversos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Taxa de Sobrevida , Vimblastina/administração & dosagem , Adulto Jovem
19.
Pediatr Blood Cancer ; 65(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28941151

RESUMO

Desmoplastic small round cell tumor (DSRCT) is a rare mesenchymal tumor that typically presents with multiple abdominal masses. Initial treatment is multimodal in nature. Patients with relapsed DSRCT have a poor prognosis, and there are no standard therapies. We report our experience with five patients treated with vinorelbine, cyclophosphamide, and temsirolimus (VCT). Median number of VCT courses delivered was 7 (range 4-14 courses), and partial response was observed in all patients. Median time to progression or relapse was 8.5 months (range 7-16 months). Neutropenia and mucositis were most common toxicities (n = 4 each).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Tumor Desmoplásico de Pequenas Células Redondas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Tumor Desmoplásico de Pequenas Células Redondas/diagnóstico por imagem , Feminino , Humanos , Masculino , Mucosite/induzido quimicamente , Mucosite/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Neutropenia/induzido quimicamente , Neutropenia/diagnóstico por imagem , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Sirolimo/análogos & derivados , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , Vinorelbina
20.
Lancet Oncol ; 19(1): 139-148, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29174310

RESUMO

BACKGROUND: Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC. METHODS: We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079. FINDINGS: Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8-44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9-32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6-22·3]; hazard ratio [HR] 0·60, 95% CI 0·42-0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related. INTERPRETATION: Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature. FUNDING: Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Vimblastina/análogos & derivados , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , China , Cisplatino/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vinorelbina , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA