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1.
Gynecol Oncol ; 156(1): 23-31, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31791552

RESUMO

OBJECTIVE: This phase 1b/2 clinical trial (NCT01663857) evaluated the efficacy of ralimetinib in combination with gemcitabine (G) and carboplatin (C), followed by maintenance ralimetinib, for patients with recurrent platinum-sensitive epithelial ovarian cancer. METHODS: Phase 1b was to determine the recommended phase 2 dose (RP2D) of ralimetinib administered Q12H on Days 1-10 (q21d) in combination with G (1000 mg/m2, Days 3 and 10) and C (AUC 4, Day 3) for six cycles. In phase 2, patients were randomized double-blind 1:1 to ralimetinib (R)+GC or placebo (P)+GC, for six cycles, followed by ralimetinib 300 mg Q12H or placebo on Days 1-14, q28d. RESULTS: 118 patients received at least one dose of ralimetinib or placebo; eight in phase 1b and 110 in phase 2 (R+GC, N = 58; P+GC, N = 52). The RP2D for R+GC was 200 mg Q12H. The study met its primary objective of a statistically significant difference in PFS (median: R+GC, 10.3 mo vs. P+GC, 7.9 mo; hazard ratio [HR] = 0.773, P = 0.2464, against a two-sided false positive rate of 0.4). Secondary objectives were not statistically significant for median overall survival (R+GC, 29.2 mo vs. P+GC, 25.1 mo; HR = 0.827, P = 0.4686) or overall response rate (R+GC 46.6% vs. P+GC, 46.2%; P = 0.9667). The safety profile of R+GC therapy was mainly consistent with safety of the chemotherapy backbone alone. Grade 3/4 elevated alanine aminotransferase was more common in the ralimetinib arm. CONCLUSIONS: Addition of ralimetinib to GC resulted in a modest improvement in PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Método Duplo-Cego , Feminino , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
2.
Ann Hematol ; 99(1): 105-112, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31776726

RESUMO

Outcome of patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) remains poor, highlighting the need for novel treatment approaches. The multicentre randomised phase II LEGEND trial evaluated lenalidomide in combination with rituximab, methylprednisolone and gemcitabine (R-GEM-L) vs. standard R-GEM-P as second-line treatment of DLBCL. The study closed early to recruitment after the planned interim analysis failed to demonstrate a complete response (CR) rate of ≥ 40% in either arm. Among 34 evaluable patients, 7/18 (38.9%) achieved CR with R-GEM-L and 3/16 (18.8%) with R-GEM-P. Median event-free and overall survival was 3.5/3.8 months and 10.8/8.3 months for R-GEM-L and R-GEM-P, respectively. The incidence of grade ≥ 3 toxicities was 52% in R-GEM-L and 83% in R-GEM-P. Efficacy and tolerability of R-GEM-L seem comparable with R-GEM-P and other standard salvage therapies, but a stringent design led to early trial closure. Combination of lenalidomide with gemcitabine-based regimens should be further evaluated in r/r DLBCL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Taxa de Sobrevida
3.
Int J Nanomedicine ; 14: 7263-7279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686807

RESUMO

Background: Gemcitabine has been widely used as a chemotherapeutic drug. However, drug resistance, short half-life and side effects seriously decrease its chemotherapeutic efficacy. Purpose: The object of preparing RGDV-gemcitabine was to prolong the half-life, to overcome drug resistance and to eliminate bone marrow toxicity of gemcitabine. Methods: Arg-Gly-Asp-Val was coupled with gemcitabine, forming 4-(Arg-Gly-Asp-Val-amino)-1-[3,3-difluoro-4-hydroxy-5-(hydroxylmethyl)oxo-lan-2-yl]pyrimidin-2-one (RGDV-gemcitabine) involving 9-step reactions. The advantages of RGDV-gemcitabine to gemcitabine were demonstrated by a series of assays, such as in vitro half-life assay, in vitro drug resistance assay, in vivo anti-tumor assay, in vivo kidney toxicity assay, in vivo liver toxicity assay and in vivo marrow toxicity assay. The nano-features of RGDV-gemcitabine were visualized by TEM, SEM and AFM images. The tumor-targeting action and release of RGDV-gemcitabine were evidenced by FT-MS spectra. Results: Half-life and anti-tumor activity of RGDV-gemcitabine were 17-fold longer and 10-fold higher than that of gemcitabine, respectively. RGDV-gemcitabine, but not gemcitabine, showed no kidney toxicity, no liver toxicity, no marrow toxicity and no drug resistance. The advantages attributed to the nanofeatures of RGDV-gemcitabine were targeting tumor tissue and releasing gemcitabine in tumor tissue. Conclusion: RGDV-gemcitabine successively overcame the defects of gemcitabine and provided a practical strategy of nano-medicine.


Assuntos
Medula Óssea/patologia , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Nanomedicina , Oligopeptídeos/farmacologia , Alanina Transaminase/sangue , Animais , Antineoplásicos/farmacologia , Aspartato Aminotransferases/sangue , Linhagem Celular Tumoral , Desoxicitidina/efeitos adversos , Desoxicitidina/síntese química , Desoxicitidina/química , Meia-Vida , Humanos , Concentração Inibidora 50 , Masculino , Camundongos Endogâmicos ICR , Oligopeptídeos/síntese química , Oligopeptídeos/química , Tamanho da Partícula , Eletricidade Estática
4.
BMC Cancer ; 19(1): 929, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533662

RESUMO

BACKGROUND: Preoperative 5-FU-based chemoradiation is currently a standard treatment for advanced rectal cancer, particularly in Western countries. Although it reduced the local recurrence, it could not necessarily improve overall survival. Furthermore, it can also produce adverse effects and long-term sphincter function deficiency. Adjuvant oxaliplatin plus capecitabine (XELOX) is a recommended regimen for patients with curatively resected colon cancer. However, the efficacy of postoperative adjuvant therapy for rectal cancer patients who have not undergone preoperative chemoradiation remains unknown. We aimed to evaluate the efficacy of surgery and postoperative XELOX without preoperative chemoradiation for treating rectal cancer. METHODS: We performed a prospective, multicenter, open-label, single arm phase II study. Patients with curatively resected high-risk stage II and stage III rectal cancer who had not undergone preoperative therapy were treated with a 120 min intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and capecitabine (2000 mg/m2/day) in 2 divided doses for 14 days of a 3-week cycle, for a total of 8 cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: Between August 2012 and June 2015, 60 men and 47 women with a median age was 63 years (range: 29-77 years) were enrolled. Ninety-three patients had Eastern Cooperative Oncology Group performance status scores of '0' and 14 had scores of '1'. Tumors were located in the upper and lower rectums in 54 and 48 patients, respectively; 8 patients had stage II disease and 99 had stage III. The 3-year DFS was 70.1% (95% confidence interval, 60.8-78.0%) and 33 patients (31%) experienced recurrence, most commonly in the lung (16 patients) followed by local recurrence (9) and hepatic recurrence (7). CONCLUSIONS: Postoperative XELOX without preoperative chemoradiation is effective for rectal cancer and provides adequate 3-year DFS prospects. TRIAL REGISTRATION: This clinical trial was registered in the University Hospital Medical Information Network registry system as UMIN000008634 at Aug 06, 2012.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Oxaliplatina/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina/efeitos adversos , Estudos Prospectivos , Neoplasias Retais/cirurgia
5.
Toxicol Lett ; 316: 20-26, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31465813

RESUMO

Health-care personnel handling antineoplastic drugs could be at risk for adverse health effects. We aimed to evaluate genotoxic and cytotoxic effects of antineoplastic drug exposure of personnel preparing and administering such drugs in three Oncology Hospitals in Italy enrolling 42 exposed subjects and 53 controls. Furthermore, we aimed to study the possible influence of XRCC1 and hOGG1 DNA repair genes polymorphisms on genotoxicity induced on buccal cells. We performed workplace and personal monitoring of some drugs and used exposure diary informations to characterize the exposure. Urinary 5-FU metabolite (α-fluoro-ß-alanine) was measured. Buccal Micronucleus Cytome (BMCyt) assay was used to evaluate DNA damage and other cellular anomalies. GEM and 5-FU contamination was found in 68% and 42% of wipe/swab samples respectively. GEM deposition was found on workers' pads while no α-fluoro-ß-alanine was found. BMCyt-assay showed higher genotoxicity and cytotoxicity on nurses administering antineoplastics than on preparators and controls. Among micronucleus (MN) positive (with MN frequency higher than 1.5‰) exposed subjects, the percentage of those carrying XRCC1 mut/het genotype was higher than in MN positive-controls. Using the sensitive BMCyt assay, we demonstrated that handling antineoplastics still represents a potential occupational health risk for workers that should be better trained/informed regarding such risks.


Assuntos
Antineoplásicos/efeitos adversos , Desoxicitidina/análogos & derivados , Monitoramento Ambiental/métodos , Fluoruracila/efeitos adversos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Mucosa Bucal/efeitos dos fármacos , Recursos Humanos de Enfermagem no Hospital , Exposição Ocupacional/efeitos adversos , Saúde do Trabalhador , Enfermagem Oncológica , Adulto , Antineoplásicos/urina , Biomarcadores/urina , Estudos de Casos e Controles , DNA Glicosilases/genética , Desoxicitidina/efeitos adversos , Desoxicitidina/urina , Feminino , Fluoruracila/urina , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/metabolismo , Exposição Ocupacional/prevenção & controle , Polimorfismo Genético , Medição de Risco , Fatores de Risco , Urinálise , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética
6.
Oncology ; 97(6): 327-333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31412347

RESUMO

BACKGROUND: There has been no study so far on gemcitabine continuous maintenance therapy targeting only squamous non-small-cell lung cancer (NSCLC) patients. This study aimed to assess the efficacy and safety of cisplatin plus gemcitabine followed by maintenance gemcitabine for chemotherapy- naïve Japanese patients with advanced squamous NSCLC. METHODS: The patients received 4 cycles of gemcitabine (1,000 mg/m2, days 1 and 8) and cisplatin (80 mg/m2, day 1) every 3 weeks, followed by gemcitabine alone as maintenance therapy every 3 weeks until disease progression or unacceptable toxicity. The primary end point of the study was progression-free survival (PFS) from the date of registration. RESULTS: From May 2013 to October 2018, 26 patients were enrolled, and 25 patients received ≥1 cycle of planned treatment. Eighteen patients (69.2%) received 4 cycles of cisplatin plus gemcitabine, and 16 patients (61.5%) received ≥1 cycle of maintenance gemcitabine. The median PFS from the date of registration was 5.3 months (95% CI 2.9-7.3 months). In 16 patients who received ≥1 cycle of maintenance gemcitabine, the median PFS from the date of maintenance gemcitabine initiation was 3.8 months (95% CI 2.3-5.2 months). Their median overall survival from the date of registration was 11.9 months (95% CI 7.5-26.5 months). During the maintenance therapy, adverse events (AEs) were mostly Common Terminology Criteria for AE grade 1. CONCLUSIONS: While this trial did not meet the primary endpoint, the sufficient efficacy and feasibility of gemcitabine maintenance therapy were suggested.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade
7.
Mol Carcinog ; 58(11): 1985-1997, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31373074

RESUMO

Growing body of evidence suggests that epithelial-mesenchymal transition (EMT) is a critical process in tumor progression and chemoresistance in pancreatic cancer (PC). The aim of this study was to analyze the role of EMT-like changes in acquisition of resistance to gemcitabine in pancreatic cells of the mesenchymal or epithelial phenotype. Therefore, chemoresistant BxPC-3, Capan-2, Panc-1, and MiaPaca-2 cells were selected by chronic exposure to increasing concentrations of gemcitabine. We show that gemcitabine-resistant Panc-1 and MiaPaca-2 cells of mesenchymal-like phenotype undergo further EMT-like molecular changes mediated by ERK-ZEB-1 pathway, and that inhibition of ERK1/2 phosphorylation or ZEB-1 expression resulted in a decrease in chemoresistance. Conversely, gemcitabine-resistant BxPC-3 and Capan-2 cells of epithelial-like phenotype did not show such typical EMT-like molecular changes although the expression of the tight junction marker occludin could be found decreased. In pancreatic cancer patients, high ZEB-1 expression was associated with tumor invasion and tumor budding. In addition, tumor budding was essentially observed in patients treated with neoadjuvant chemotherapy. These findings support the notion that gemcitabine treatment induces EMT-like changes that sustain invasion and chemoresistance in PC cells.


Assuntos
Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/efeitos adversos , Desoxicitidina/farmacologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fenótipo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
8.
Intern Med ; 58(20): 2957-2962, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31243233

RESUMO

Gemcitabine plus nab-paclitaxel is the current standard chemotherapy for patients with metastatic pancreatic cancer. We conducted a phase I/II study in Japan, in which high response rates and manageable toxicity were observed. In this study, two patients were reported as experiencing pancreatitis due to chemotherapy. In general, pancreatitis is sometimes observed when the tumor involves the pancreatic duct, and the onset is observed before the diagnosis or at the initial stage. The onset of pancreatitis in these cases was unique and observed after the start of chemotherapy. Pancreatitis may be induced by the alleviation of stenosis of the pancreatic duct associated with tumor shrinkage.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/secundário , Neoplasias Pancreáticas/tratamento farmacológico , Pancreatite/induzido quimicamente , Doença Aguda , Idoso , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/diagnóstico por imagem , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Pancreatite/diagnóstico por imagem , Tomografia Computadorizada por Raios X
9.
N Engl J Med ; 381(12): 1124-1135, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31150573

RESUMO

BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Adolescente , Adulto , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Análise de Sobrevida , Adulto Jovem
10.
Int J Biol Macromol ; 136: 1169-1175, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170489

RESUMO

Gemcitabine (2'-deoxy-2',2'-difluorocytidine, dFdC) is one of the most effective chemotherapy drugs commonly used for treatment of various tumors. Despite its significant anticancer effects, some adverse effects create obstacles to treatment. The main toxicity of gemcitabine is myelosuppression, which not only reduces patient quality of life, but also hinders further anticancer treatment. In this respect, immunotherapy can address these drawbacks because of its ability to enhance the patient's immune system. To improve immune system function, yeast-derived ß-glucans, which are well-known biologic response modifiers, were administered to gemcitabine-treated mice. The in vivo experiment revealed that orally administered yeast (1 → 3)-(1 → 6)-ß-d-glucan effectively alleviated myelosuppression associated with gemcitabine-induced pancytopenia. Moreover, analysis of myelopoiesis-related cytokine expression through real-time PCR demonstrated that ß-glucan treatment significantly upregulated hematopoietic responses in gemcitabine-treated mice. Furthermore, orally administered ß-glucan significantly induced the expression of IFN-γ and IL-2 in splenocytes of gemcitabine-treated mice. It also restored the cytotoxicity of splenocytes against YAC-1 in gemcitabine-treated mice and displayed a positive effect on gemcitabine-damaged bone marrow tissue. In conclusion, yeast ß-glucans have the potential to be used as adjuvants for alleviating chemotherapy-induced immunosuppression in patients.


Assuntos
Desoxicitidina/análogos & derivados , Imunossupressão/efeitos adversos , Leveduras/química , beta-Glucanas/farmacologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Linhagem Celular Tumoral , Citocinas/metabolismo , Desoxicitidina/efeitos adversos , Desoxicitidina/antagonistas & inibidores , Hematopoese/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pancitopenia/induzido quimicamente , Pancitopenia/tratamento farmacológico , Pancitopenia/imunologia , Baço/efeitos dos fármacos , Baço/imunologia , beta-Glucanas/uso terapêutico
11.
JAMA Oncol ; 5(7): 993-998, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31120501

RESUMO

Importance: Autophagy is a mechanism of treatment resistance to chemotherapy that has a role in the maintenance of pancreatic cancer. Hydroxychloroquine sulfate (HCQ) is an inhibitor of autophagy that inhibits the fusion of the autophagosome to the lysosome. Objective: To determine whether HCQ improves overall survival at 1 year in combination with gemcitabine hydrochloride and nab-paclitaxel (GA) among patients with metastatic pancreatic cancer. Design, Setting, and Participants: Open-label, phase 2 randomized clinical trial conducted between March 18, 2013, and November 16, 2017, at the University of Pennsylvania, HonorHealth, and The Johns Hopkins University among 112 patients with previously untreated metastatic or advanced pancreatic ductal adenocarcinoma, Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate marrow and organ function. All efficacy analyses were performed for the intention-to-treat population. Interventions: Patients were randomized in a 1:1 ratio to receive GA with or without HCQ. All patients received standard doses of GA, and those randomized to receive HCQ were treated continuously with 600 mg orally twice daily. Main Outcome and Measure: Overall survival at 1 year. Results: A total of 112 patients (45 women and 67 men; median age, 65 years; range, 43-86 years) were enrolled; 55 were randomized to receive GA plus HCQ, and 57 to receive GA. Overall survival at 12 months was 41% (95% CI, 27%-53%) in the HCQ group and 49% (95% CI, 35%-61%) in the non-HCQ group. Median progression-free survival was 5.7 months (95% CI, 4.0-9.3 months) in the HCQ group and 6.4 months (95% CI, 4.5-7.6 months) in the non-HCQ group. Median overall survival was 11.1 months (95% CI, 9.0-14.2 months) in the HCQ group and 12.1 months (95% CI, 9.3-15.5 months) in the non-HCQ group. Overall response rate was 38.2% (n = 21) in the HCQ group and 21.1% (n = 12) in the non-HCQ group (P = .047). Treatment-related grade 3 or 4 adverse events that differed between the HCQ and non-HCQ groups were neutropenia (23 of 54 [42.6%] vs 12 of 53 [22.6%]), anemia (2 of 54 [3.7%] vs 9 of 53 [17.0%]), fatigue (4 of 54 [7.4%] vs 0), nausea (5 of 54 [9.3%] vs 0), peripheral neuropathy (7 of 54 [13.0%] vs 3 of 53 [5.7%]), visual changes (3 of 54 [5.6%] vs 0), and neuropsychiatric symptoms (3 of 54 [5.6%] vs 0). Conclusions and Relevance: The addition of HCQ to block autophagy did not improve the primary end point of overall survival at 12 months. These data do not support the routine use of GA plus HCQ for metastatic pancreatic cancer in the absence of a biomarker. However, improvement seen in the overall response rate with HCQ may indicate a role for HCQ in the locally advanced setting, where tumor response may permit resection. Trial Registration: ClinicalTrials.gov identifier: NCT01506973.


Assuntos
Albuminas/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Hidroxicloroquina/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hidroxicloroquina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Resultado do Tratamento
12.
Cancer Commun (Lond) ; 39(1): 29, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138332

RESUMO

BACKGROUND: A phase II clinical trial of the comparison between eribulin plus gemcitabine (EG) and paclitaxel plus gemcitabine (PG) as first-line chemotherapy for patients with metastatic breast cancer (MBC) found that the EG regimen was less neurotoxic, but was similar in efficacy to the PG regimen. In the present study, we analyzed functional assessment of cancer therapy-taxane (FACT-Taxane) questionnaires from patients in this clinical trial to determine their quality of life (QoL). METHODS: QoL was assessed using the Korean version of the FACT-Taxane questionnaires. After baseline assessment, QoL was assessed every 2 cycles for 12 cycles and every 3 cycles thereafter. The linear mixed model was used to evaluate the difference in QoL between the EG and PG arms. RESULTS: Of the 118 enrolled patients, 117 responded to the FACT-Taxane questionnaires at baseline, 1 in the PG arm did not. Baseline QoL scores were not different between the EG and PG arms. During treatment, taxane subscale scores were significantly higher in the PG arm than in the EG arm after 2-13 cycles of chemotherapy (all P < 0.05), except for the 11th cycle. Neuropathy-specific analysis showed that patients in the PG arm had earlier and more severe neuropathic symptoms than those in the EG arm (P < 0.001). CONCLUSIONS: In our QoL analysis, the EG regimen delayed and decreased neuropathy as compared with the PG regimen. Therefore, eribulin would be a reasonable substitute for paclitaxel as first-line chemotherapy for MBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Furanos/administração & dosagem , Cetonas/administração & dosagem , Paclitaxel/administração & dosagem , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Furanos/efeitos adversos , Humanos , Cetonas/efeitos adversos , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Receptor ErbB-2 , República da Coreia , Inquéritos e Questionários
13.
BMJ Case Rep ; 12(4)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30962211

RESUMO

A woman in her mid-70s with metastatic pancreatic adenocarcinoma presented with fatigue, nausea and bilateral leg swelling, 4 days after an intravenous gemcitabine infusion. Additional examination and laboratory tests showed mild hypertension, low haemoglobin, high lactate dehydrogenase, low platelet count and high serum creatinine. The patient was subsequently diagnosed with haemolytic uraemic syndrome (HUS), and gemcitabine administration was immediately ceased. The patient received a 5-day course of methylprednisolone, with a full recovery being made 10 days after diagnosis. Clinicians should be aware of the rare but serious complication of gemcitabine-induced HUS (GiHUS), as early diagnosis and management, which includes prompt discontinuation of gemcitabine, are crucial in promptly resolving this condition. This case report describes one treatment that can be used for the treatment of GiHUS, while briefly covering some other novel treatments that have been described in other studies.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/efeitos adversos , Desoxicitidina/análogos & derivados , Síndrome Hemolítico-Urêmica/etiologia , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Síndrome Hemolítico-Urêmica/terapia , Humanos , Metilprednisolona/administração & dosagem , Paclitaxel/administração & dosagem
14.
JAMA Oncol ; 5(6): 824-830, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30998813

RESUMO

Importance: Administration of gemcitabine-cisplatin, the current standard therapy for advanced biliary tract cancers, results in median progression-free survival and overall survival of 8.0 and 11.7 months, respectively. New treatments offering improved survival outcomes are therefore needed. Objective: To evaluate the association between progression-free survival and the addition of nanoparticle albumin-bound (nab)-paclitaxel to gemcitabine-cisplatin for the treatment of patients with advanced biliary tract cancer. Design, Setting, and Participants: This open-label, single-arm, phase 2 clinical trial conducted at the University of Texas MD Anderson Cancer Center and the Mayo Clinic in Phoenix, Arizona, enrolled 62 patients with advanced biliary tract cancers between April 14, 2015, and April 24, 2017. Interventions: Patients initially received gemcitabine, 1000 mg/m2, cisplatin, 25 mg/m2, and nab-paclitaxel, 125 mg/m2, on days 1 and 8 of 21-day cycles. Owing to hematologic adverse events among the first 32 patients enrolled, these starting doses were reduced to 800, 25, and 100 mg/m2, respectively, for the remaining 28 patients. Main Outcomes and Measures: The primary trial end point was investigator-assessed progression-free survival in the intention-to-treat population. Results: Of 60 patients who started treatment, the mean (SD) age was 58.4 (11.0) years, 38 (63%) had intrahepatic cholangiocarcinoma, 9 (15%) had extrahepatic cholangiocarcinoma, 13 (22%) had gallbladder cancer, 47 (78%) had metastatic disease, and 13 (22%) had locally advanced disease. Median follow-up was 12.2 (95% CI, 9.4-19.4) months, and median progression-free survival was 11.8 (95% CI, 6.0 to 15.6) months. The partial response rate was 45%, and the disease control rate was 84%. Median overall survival was 19.2 months (95% CI, 13.2 months to not estimable). Patients in the safety population (n = 57) received a median of 6 (interquartile range, 3-11) cycles of treatment; 26 patients (46%) remained on their starting dose throughout the trial. Grade 3 or higher adverse events occurred in 58% of patients, and 9 patients (16%) withdrew owing to adverse events. Neutropenia was the most common grade 3 or higher adverse event, occurring in 19 patients (33%) overall. Post hoc analyses showed that treatment efficacy was not significantly associated with starting dose, tumor type, or disease status and that tolerability was improved with reduced- vs high-dose treatment. Conclusions and Relevance: Treatment with nab-paclitaxel plus gemcitabine-cisplatin prolonged median progression-free survival and overall survival vs those reported for historical controls treated with gemcitabine-cisplatin alone. These findings will be tested in a phase 3 randomized clinical trial. Trial Registration: ClinicalTrials.gov identifier: NCT02392637.


Assuntos
Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Paclitaxel/uso terapêutico , Idoso , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Resultado do Tratamento
15.
Farm. hosp ; 43(2): 56-60, mar.-abr. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-182591

RESUMO

Objetivo: Evaluar y comparar la calidad de vida de pacientes con cáncer colorrectal no metastásico tratados con el esquema FOLFOX o XELOX. Método: Estudio descriptivo prospectivo de 24 meses de duración (octubre 2015-octubre 2017) en pacientes con cáncer colorrectal no metastásico en tratamiento quimioterápico adyuvante. Se pasó a los pacientes el cuestionario de calidad de vida EORTC QLQ-C30 al inicio del tratamiento y a las 12 semanas. Variables recogidas: exposición (esquema quimioterápico), control (datos demográficos, de la enfermedad y del tratamiento) y respuesta (puntuaciones del cuestionario). El análisis estadístico se efectuó con el programa SPSS(R) 15.0. Resultados: Se incluyeron 30 pacientes, encontrándose diferencias estadísticamente significativas en el ítem rol emocional a las 12 semanas de tratamiento (FOLFOX 92 puntos versus XELOX 82 puntos; p = 0,036). Además, los pacientes tratados con FOLFOX presentaron un empeoramiento clínicamente relevante en actividades cotidianas, estreñimiento e insomnio; mientras que los tratados con XELOX mostraron un empeoramiento clínicamente relevante en actividades cotidianas, estreñimiento, fatiga, náuseas, vómitos, anorexia y diarrea. Conclusiones: Los pacientes tratados con el esquema XELOX se encontraron peor emocionalmente a las 12 semanas del tratamiento adyuvante que los tratados con FOLFOX y presentaron empeoramiento en fatiga, náuseas, vómitos, anorexia y diarrea


Objective: To evaluate and to compare quality of life of patients with non-metastasic colorectal cancer treated either with FOLFOX or with XELOX scheme. Method: Descriptive prospective study during 24 months (October 2015-October 2017) for patients with non-metastasic colorectal cancer in chemotherapy adyuvant treatment. EORTC QLQ-C30 questionnaire was filled by patients at the beginning and at week 12 of adjuvant treatment. Variables collected: exposure (chemotherapeutic scheme administered), control (demographic data, disease data, treatment data) and response (scores obtained from the questionnaire). The data statistical analysis was carried out with the SPSS(R) 15.0 programme. Results: 30 patients were included. Statistically significant differences were found in emotional role item at the middle of the treatment (FOLFOX 92 points vs. XELOX 82 points; p = 0,036). Patients with FOLFOX presented a clinically relevant worsening in terms of daily activities, constipation and insomnia. Patients treated with XELOX a clinically relevant worsening in daily activities, constipation, fatigue, nausea, vomiting, anorexia and diarrhoea were observed. Conclusions: Patients with XELOX scheme referred to have worse emotionally status in the middle of the adjuvant treatment than patients treated with FOLFOX scheme and presented a worsening in items fatigue, nausea, vomiting, anorexia and diarrhoea


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/psicologia , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Qualidade de Vida , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Fluoruracila/uso terapêutico , Fluoruracila/efeitos adversos , Compostos Organoplatínicos/efeitos adversos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento
16.
Farm Hosp ; 43(2): 56-60, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30848178

RESUMO

OBJECTIVE: To evaluate and to compare quality of life of patients with non- metastasic colorectal cancer treated either with FOLFOX or with XELOX  scheme. METHOD: Descriptive prospective study during 24 months (October 2015- October 2017) for patients with non-metastasic colorectal cancer in chemotherapy adyuvant treatment. EORTC QLQ-C30 questionnaire was filled by patients at the beginning and at week 12 of adjuvant treatment. Variables collected: exposure (chemotherapeutic scheme administered), control (demographic data, disease data, treatment data) and response (scores obtained from the questionnaire). The data statistical  analysis was carried out with the SPSS® 15.0 programme. RESULTS: 30 patients were included. Statistically significant differences were  found in emotional role item at the middle of the treatment (FOLFOX 92  points vs. XELOX 82 points; p = 0,036). Patients with FOLFOX presented a  clinically relevant worsening in terms of daily activities, constipation and  insomnia. Patients treated with XELOX a clinically relevant worsening in daily  activities, constipation, fatigue, nausea, vomiting, anorexia and diarrhoea were observed. CONCLUSIONS: Patients with XELOX scheme referred to have worse  emotionally status in the middle of the adjuvant treatment than patients  treated with FOLFOX scheme and presented a worsening in items fatigue,  nausea, vomiting, anorexia and diarrhoea.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/psicologia , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Qualidade de Vida , Adulto , Idoso , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Emoções , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
17.
Oncology ; 96(4): 217-222, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30844808

RESUMO

OBJECTIVES: Tissue factor overexpression is associated with tumor progression, venous thromboembolism, and worsened survival in patients with cancer. Tissue factor and activated factor VII (FVIIa) complex may contribute to tumor invasiveness by promoting cell migration and angiogenesis. The study objective was to evaluate safety, pharmacokinetics, and efficacy of PCI-27483, a selective FVIIa inhibitor. METHODS: This was an open-label, multicenter phase 2 trial of patients with advanced pancreatic cancer. Part A of the study was an intrapatient dose escalation lead-in portion in patients concurrently receiving gemcitabine, and in part B, patients were randomized 1: 1 to the recommended phase 2 dose combination PCI-27483-gemcitabine versus gemcitabine alone. RESULTS: Target international normalized ratio (between 2.0-3.0) was achieved following PCI-27483 treatment. Overall safety of PCI-27483-gemcitabine (n = 26) was similar to gemcitabine alone (n = 16), with a higher incidence of mostly low-grade bleeding events (65% vs. 19%). Progression-free survival (PFS) and overall survival (OS) were not significantly different between patients treated with PCI-27483-gemcitabine (PFS: 3.7 months, OS: 5.7 months) and those treated with gemcitabine alone (PFS: 1.9 months, OS: 5.6 months). CONCLUSIONS: Targeted inhibition of the coagulation cascade was achieved by administering PCI-27483. PCI-27483-gemcitabine was well tolerated, but superiority to single agent gemcitabine was not demonstrated.


Assuntos
Anticoagulantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácido Aspártico/análogos & derivados , Benzimidazóis/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fator VIIa/antagonistas & inibidores , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácido Aspártico/administração & dosagem , Ácido Aspártico/efeitos adversos , Ácido Aspártico/farmacocinética , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacocinética , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/secundário , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Monitoramento de Medicamentos/métodos , Fator VIIa/metabolismo , Feminino , Hemorragia/induzido quimicamente , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Intervalo Livre de Progressão , Fatores de Tempo
18.
J Clin Oncol ; 37(8): 658-667, 2019 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-30707660

RESUMO

PURPOSE: No standard adjuvant treatment currently is recommended in localized biliary tract cancer (BTC) after surgical resection. We aimed to assess whether gemcitabine and oxaliplatin chemotherapy (GEMOX) would increase relapse-free survival (RFS) while maintaining health-related quality of life (HRQOL) in patients who undergo resection. PATIENTS AND METHODS: We performed a multicenter, open-label, randomized phase III trial in 33 centers. Patients were randomly assigned (1:1) within 3 months after R0 or R1 resection of a localized BTC to receive either GEMOX (gemcitabine 1,000 mg/m2 on day 1 and oxaliplatin 85 mg/m2 infused on day 2 of a 2-week cycle) for 12 cycles (experimental arm A) or surveillance (standard arm B). Primary end points were RFS and HRQOL. RESULTS: Between July 2009 and February 2014, 196 patients were included. Baseline characteristics were balanced between the two arms. After a median follow-up of 46.5 months (95% CI, 42.6 to 49.3 months), 126 RFS events and 82 deaths were recorded. There was no significant difference in RFS between the two arms (median, 30.4 months in arm A v 18.5 months in arm B; hazard ratio [HR], 0.88; 95% CI, 0.62 to 1.25; P = .48). There was no difference in time to definitive deterioration of global HRQOL (median, 31.8 months in arm A v 32.1 months in arm B; HR, 1.28; 95% CI, 0.73 to 2.26; log-rank P = .39). Overall survival was not different (median, 75.8 months in arm A v 50.8 months in arm B; HR, 1.08; 95% CI, 0.70 to 1.66; log-rank P = .74). Maximal adverse events were grade 3 in 62% (arm A) versus 18% (arm B) and grade 4 in 11% versus 3% ( P < .001). CONCLUSION: There was no benefit of adjuvant GEMOX in resected BTC despite adequate tolerance and delivery of the regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar , Desoxicitidina/análogos & derivados , Oxaliplatina/administração & dosagem , Conduta Expectante , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Procedimentos Cirúrgicos do Sistema Biliar/mortalidade , Quimioterapia Adjuvante , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/efeitos adversos , Intervalo Livre de Progressão , Qualidade de Vida , Fatores de Tempo
19.
Future Oncol ; 15(12): 1295-1302, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30768369

RESUMO

Napabucasin (also known as BBI-608 or BBI608) is an investigational, oral agent hypothesized to inhibit multiple oncogenic pathways. In this article, we describe the design and rationale for the CanStem111P clinical trial, a multicenter, randomized, open-label, Phase III study designed to determine the efficacy and safety of combining napabucasin with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma (NCT02993731). Patients were randomized in a 1:1 fashion to receive weekly gemcitabine and nab-paclitaxel with or without napabucasin. The results of this study will help define the role of this novel agent in the management of advanced pancreatic cancer.


Assuntos
Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzofuranos/administração & dosagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Naftoquinonas/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Administração Oral , Adulto , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzofuranos/efeitos adversos , Carcinoma Ductal Pancreático/mortalidade , Ensaios Clínicos Fase III como Assunto , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Esquema de Medicação , Humanos , Estudos Multicêntricos como Assunto , Naftoquinonas/efeitos adversos , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/mortalidade , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
20.
BMC Cancer ; 19(1): 151, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764783

RESUMO

BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a potentially serious complication that can lead to chemotherapy dose delays, dose reductions, or discontinuation, and increases the risk of serious bleeding events. The objectives of this study were to characterize the incidence, clinical consequences, and economic costs of CIT in current US clinical practice. METHODS: A retrospective cohort design and data from two US private healthcare claims repositories (01/2010-12/2016) were employed. Study population comprised adults who received selected myelosuppressive chemotherapy regimens for solid tumors or non-Hodgkin's lymphoma. CIT was identified based on: diagnosis code for thrombocytopenia or bleeding; procedure code for platelet transfusion or bleeding control; or drug code for thrombopoietin-receptor agonist. Incidence of CIT was evaluated during the chemotherapy course (max. no. cycles = 8), and associated consequences and costs (2016US$) were evaluated during the cycle of the CIT episode. RESULTS: Among 215,508 cancer chemotherapy patients, CIT incidence during the course (mean no. cycles = 4.6) was 9.7% (95% CI: 9.6-9.8), and ranged from 6.1% (5.9-6.3) for regimens containing cyclophosphamide to 13.5% (12.7-14.3) for regimens containing gemcitabine; among all patients, incidence was 2.7% (2.6-2.8) in cycle 1, 2.7% (2.6-2.8) in cycle 2, and 2.9% (2.9-3.0) in cycles thereafter. One-third of CIT episodes were managed in hospital, and for the subset of patients hospitalized with a first-listed diagnosis of CIT, mean length of stay was 4.6 (4.4-5.0) days and mean cost of inpatient care was $36,448 (32,332-41,331). Across cycles with CIT, mean cost of CIT-related care was $2179 (2029-2329), comprising $1024 (881-1167) for inpatient care and $1153 (1119-1187) for outpatient care. CONCLUSIONS: In this retrospective evaluation of cancer chemotherapy patients, CIT incidence was high, especially among patients receiving gemcitabine-based regimens, and the costs of CIT-related care were substantial. Accordingly, interventions aimed at identifying and targeting high-risk patients for preventative measures may yield substantial clinical and economic benefits.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Trombocitopenia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Hospitalização , Humanos , Incidência , Quimioterapia de Indução/efeitos adversos , Tempo de Internação , Estudos Retrospectivos , Risco , Trombocitopenia/etiologia , Estados Unidos/epidemiologia
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