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2.
Ann Hematol ; 99(11): 2589-2598, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32892275

RESUMO

The induction therapy containing ixazomib, an oral proteasome inhibitor, has shown favorable efficacy and safety in clinical trials, but its experience in real-life remains limited. In routine practice, few patients received ixazomib-based induction therapy due to reasons including (1) patients' preference on oral regimens, (2) concerns on adverse events (AEs) of other intravenous/subcutaneous regimens, (3) requirements for less center visits, and (4) fears of COVID-19 and other infectious disease exposures. With the aim of assessing the real-life effectiveness and safety of ixazomib-based induction therapy, we performed this multi-center, observational study on 85 newly diagnosed multiple myeloma (NDMM) patients from 14 medical centers. Ixazomib-based regimens included ixazomib-lenalidomide-dexamethasone (IRd) in 44.7% of patients, ixazomib-dexamethasone (Id) in 29.4%, and Id plus another agent (doxorubicin, cyclophosphamide, thalidomide, or daratumumab) in 25.9%. Different ixazomib-based therapies were applied due to (1) financial burdens or limitations on local health insurance coverage, (2) concerns on treatment tolerance, and (3) drug accessibility issue. Ten patients received ixazomib maintenance. The median age was 67 years; 43.5% had ISS stage III disease; 48.2% had an Eastern Cooperative Oncology Group performance score ≥ 2; and 17.6% with high-risk cytogenetic abnormalities. Overall response rate for all 85 patients was 95.3%, including 65.9% very good partial response or better and 29.5% complete responses. The median time to response was 30 days. The response rate was similar across different ixazomib-based regimens. Median progression-free survival was not reached. Severe AEs (≥ grade 3) were reported in 29.4% of patients. No grade 3/4 peripheral neuropathy (PN) occurred. Patients received a median of 6 (range 1-20) cycles of ixazomib treatment; 56.6% remained on treatment at data cutoff; 15.3% discontinued treatment due to intolerable AEs. These results support that the ixazomib-based frontline therapy was highly effective with acceptable toxicity in routine practice and the ixazomib oral regimens could be good alternative options for NDMM patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Compostos de Boro/administração & dosagem , Glicina/análogos & derivados , Mieloma Múltiplo/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos de Boro/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Glicina/administração & dosagem , Glicina/efeitos adversos , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/fisiopatologia , Indução de Remissão , Análise de Sobrevida , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Resultado do Tratamento
3.
Anticancer Res ; 40(9): 5295-5299, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878820

RESUMO

BACKGROUND: To assess the prophylactic efficacy of postoperative single intravesical instillation with pirarubicin (THP) and mitomycin C (MMC) for low-risk non-muscle-invasive bladder cancer (NMBC). PATIENTS AND METHODS: A total of 103 clinically low-risk NMBC patients were preoperatively randomized into either THP (n=49) or MMC (n=54) groups. The primary endpoint was recurrence-free survival. RESULTS: The median follow-up periods of the THP and MMC groups were 955 and 1008 days, respectively (p=0.76). Twelve patients (24.5%) in the THP group and 7 (13%) in the MMC group had bladder cancer recurrences. The two-year recurrence-free survival of the THP group and the MMC group was 77.8% and 86.4%, respectively (p=0.20). Neither groups had severe toxicity. CONCLUSION: In low-risk NMBC, the prophylactic effect against postoperative single intravesical instillation with THP was not superior to that with MMC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cuidados Pós-Operatórios , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Cistoscópios , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Gradação de Tumores , Estadiamento de Neoplasias , Recidiva , Resultado do Tratamento , Carga Tumoral , Neoplasias da Bexiga Urinária/diagnóstico
4.
Zhonghua Zhong Liu Za Zhi ; 42(8): 692-696, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867464

RESUMO

Objective: To evaluate the efficacy and safety of polyethylene glycol liposome doxorubicin (PLD) in the treatment of osteosarcoma. Methods: This study was a single-center retrospective clinical study. Two hundreds and seventy-six classical osteosarcoma treated in Beijing Jishuitan Hospital from 2015 to 2016 were enrolled. There were 213 patients who received combined chemotherapy of high dose methotrexate, ifosfamide, cisplatin and doxorubicin (ADM) were classified in ADM group. Other 63 patients received the same types, doses and cycles of chemotherapy drugs except ADM replaced by PLD were identified as PLD group. Clinical and imaging evaluation and surgical treatment were performed after neoadjuvant chemotherapy. Tumor necrosis rate was examined according to Huvos method. The efficacy of neoadjuvant chemotherapy was evaluated based on 90% necrosis rate. The recurrence, metastasis and survival were followed up regularly after operation. The adverse reactions of hematology, hepatorenal toxicity, gastrointestinal reaction and cardiotoxicity were evaluated. Results: There were no significant differences between PLD group and ADM group in age, sex, location, stage and surgical margin (all P>0.05). There were no significant differences in clinical symptoms and imaging evaluation between PLD group and ADM group after preoperative chemotherapy (all P>0.05). The tumor necrosis rate was detected in 134 cases. Among 27 cases of PLD group, tumor necrosis rates more than 90% were 11 cases, while among 107 cases of ADM group, tumor necrosis rates more than 90% were 45 cases. No significant difference of tumor necrosis rate between this two group was observed (P=0.901). The recurrence rates of PLD group and ADM group were 7.8% (4/51) and 7.3% (12/164), the metastasis rates were 19.6% (10/51) and 16.5% (27/164), the median progression free survival (PFS) were 42 and 37 months, respectively, without significant differences (all P>0.05). The incidence of granulocytopenia and decrease degree of granulocytes in PLD group were significantly lower than those in ADM group (P<0.001). There were no significant differences in the incidences of thrombocytopenia, anemia, gastrointestinal reaction, liver function damage and stomatitis between two groups (all P>0.05). Conclusions: PLD and ADM have similar chemotherapeutic effects in osteosarcoma. The incidences of adverse reactions of PLD are lower, especially the hematological toxicity represented by granulocytopenia is significantly reduced. PLD has a better application prospect.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/terapia , Lipossomos/uso terapêutico , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/patologia , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Extremidades , Humanos , Ifosfamida/administração & dosagem , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteossarcoma/patologia , Polietilenoglicóis , Prognóstico , Estudos Retrospectivos
5.
Lancet ; 396(10257): 1090-1100, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-32966830

RESUMO

BACKGROUND: Preferred neoadjuvant regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. IMpassion031 compared efficacy and safety of atezolizumab versus placebo combined with nab-paclitaxel followed by doxorubicin plus cyclophosphamide as neoadjuvant treatment for early-stage TNBC. METHODS: This double-blind, randomised, phase 3 study enrolled patients in 75 academic and community sites in 13 countries. Patients aged 18 years or older with previously untreated stage II-III histologically documented TNBC were randomly assigned (1:1) to receive chemotherapy plus intravenous atezolizumab at 840 mg or placebo every 2 weeks. Chemotherapy comprised of nab-paclitaxel at 125 mg/m2 every week for 12 weeks followed by doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 every 2 weeks for 8 weeks, which was then followed by surgery. Stratification was by clinical breast cancer stage and programmed cell death ligand 1 (PD-L1) status. Co-primary endpoints were pathological complete response in all-randomised (ie, all randomly assigned patients in the intention-to-treat population) and PD-L1-positive (ie, patients with PD-L1-expressing tumour infiltrating immune cells covering ≥1% of tumour area) populations. This study is registered with ClinicalTrials.gov (NCT03197935), Eudra (CT2016-004734-22), and the Japan Pharmaceutical Information Center (JapicCTI-173630), and is ongoing. FINDINGS: Between July 7, 2017, and Sept 24, 2019, 455 patients were recruited and assessed for eligibility. Of the 333 eligible patients, 165 were randomly assigned to receive atezolizumab plus chemotherapy and 168 to placebo plus chemotherapy. At data cutoff (April 3, 2020), median follow-up was 20·6 months (IQR 8·7-24·9) in the atezolizumab plus chemotherapy group and 19·8 months (8·1-24·5) in the placebo plus chemotherapy group. Pathological complete response was documented in 95 (58%, 95% CI 50-65) patients in the atezolizumab plus chemotherapy group and 69 (41%, 34-49) patients in the placebo plus chemotherapy group (rate difference 17%, 95% CI 6-27; one-sided p=0·0044 [significance boundary 0·0184]). In the PD-L1-positive population, pathological complete response was documented in 53 (69%, 95% CI 57-79) of 77 patients in the atezolizumab plus chemotherapy group versus 37 (49%, 38-61) of 75 patients in the placebo plus chemotherapy group (rate difference 20%, 95% CI 4-35; one-sided p=0·021 [significance boundary 0·0184]). In the neoadjuvant phase, grade 3-4 adverse events were balanced and treatment-related serious adverse events occurred in 37 (23%) and 26 (16%) patients, with one patient per group experiencing an unrelated grade 5 adverse event (traffic accident in the atezolizumab plus chemotherapy group and pneumonia in the placebo plus chemotherapy group). INTERPRETATION: In patients with early-stage TNBC, neoadjuvant treatment with atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy significantly improved pathological complete response rates with an acceptable safety profile. FUNDING: F Hoffmann-La Roche/Genentech.


Assuntos
Albuminas/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Método Duplo-Cego , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante
6.
Int J Nanomedicine ; 15: 5279-5288, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801691

RESUMO

Introduction: Today, a new paradigm has emerged for cancer treatment introducing combination therapies. Doxil, a liposomal doxorubicin serving as a chemotherapeutic agent, is an effective immunogenic killer of cancer cells. Anti-CTLA-4 has been approved for the treatment of some cancers, including melanoma, but side effects have limited its therapeutic potential. Methods: In this study, two approaches were utilized to increase treatment efficiency and decrease the side effects of anti-CTLA-4, combining it with chemotherapy and encapsulation in a PEGylated liposome. A different sequence of anti-CTLA-4 and Doxil was assessed in combination therapy using non-liposomal and liposomal anti-CTLA-4. Results: Our results showed that liposomal anti-CTLA-4 reduced the size of established tumors and increased survival in comparison with non-liposomal anti-CTLA-4 in a well-established B16 mouse melanoma model. In combination therapy with Doxil, only the administration of anti-CTLA-4 before Doxil showed synergism in both non-liposomal and liposomal form and increased the CD8+/regulatory T cell ratio. Discussion: In summary, our results demonstrate the potential of utilizing a nanocarrier system for the delivery of checkpoint blockers, such as anti-CTLA-4 which further showed potential in a combination therapy, especially when administered before chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antígeno CTLA-4/antagonistas & inibidores , Melanoma Experimental/tratamento farmacológico , Animais , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Antígeno CTLA-4/imunologia , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Lipossomos/química , Camundongos Endogâmicos C57BL , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Linfócitos T Reguladores/efeitos dos fármacos
7.
Ann Hematol ; 99(10): 2429-2436, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32839869

RESUMO

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Agonistas dos Canais de Cloreto/uso terapêutico , Constipação Intestinal/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Lubiprostona/uso terapêutico , Linfoma/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Alcaloides de Vinca/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Constipação Intestinal/induzido quimicamente , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Avaliação de Medicamentos , Quimioterapia Combinada , Famotidina/uso terapêutico , Feminino , Humanos , Laxantes/farmacologia , Laxantes/uso terapêutico , Óxido de Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Entorpecentes/efeitos adversos , Prednisona/administração & dosagem , Pontuação de Propensão , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Senosídeos/uso terapêutico , Alcaloides de Vinca/administração & dosagem , Vincristina/administração & dosagem
8.
Int J Nanomedicine ; 15: 5083-5095, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764938

RESUMO

Background: ß-glucans are chiral polysaccharides with well-defined immunological properties and supramolecular wrapping ability of its chiral feature. However, the exploitation of chiral properties of these nanoparticles in drug delivery systems was seldom conducted. Methods: ß-glucan molecules with different chain lengths were extracted from yeast Saccharomyces cerevisiae and thereafter modified. In a conformation transition process, these ß-glucan molecules were then self-assembled with anti-cancer drug doxorubicin into nanoparticles to construct drug delivery systems. The chiral interactions between the drug and carriers were revealed by circular dichroism spectra, ultraviolet and visible spectrum, fourier transform infrared spectroscopy, dynamic light scattering and transmission electron microscope. The immune-potentiation properties of modified ß-glucan nanoparticles were evaluated by analysis of the mRNA expression in RAW264.7 cell model. Further, the antitumor efficacy of the nanoparticles against the human breast cancer were studied in MCF-7 cell model by cellular uptake and cytotoxicity experiments. Results: ß-glucan nanoparticles can activate macrophages to produce immune enhancing cytokines (IL-1ß, IL-6, TNF-α, IFN-γ). A special chirality of the carriers in diameter of 50~160 nm can also associate with higher drug loading ability of 13.9% ~38.2% and pH-sensitive release with a change of pH from 7.4 to 5.0. Cellular uptake and cytotoxicity experiments also prove that the chiral-active ß-glucan nanoparticles can be used in anti-cancer nanomedicine. Conclusion: This work demonstrates that ß-glucans nanoparticles with special chiral feature which leading to strong immunopotentiation ability and high drug loading efficiency can be developed as a novel type of nanomedicine for anti-cancer treatment.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , beta-Glucanas/imunologia , Adjuvantes Imunológicos/química , Animais , Antineoplásicos/imunologia , Dicroísmo Circular , Portadores de Fármacos/química , Humanos , Células MCF-7 , Camundongos , Nanopartículas/química , Células RAW 264.7 , Saccharomyces cerevisiae/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Estereoisomerismo , beta-Glucanas/química
9.
PLoS One ; 15(8): e0238183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857815

RESUMO

Lymphoma (lymphosarcoma) is the second most frequent cancer in dogs and is clinically comparable to human non-Hodgkin lymphoma. Factors affecting canine lymphoma progression are unknown and complex, but there is evidence that genetic mutations play an important role. We employed Next Gen DNA sequencing of six dogs with multicentric B-cell lymphoma undergoing CHOP chemotherapy to identify genetic variations potentially impacting response. Paired samples from non-neoplastic tissue (blood mononuclear cells) and lymphoma were collected at the time of diagnosis. Cases with progression free survival above the median of 231 days were grouped as 'good' responders and cases below the median were categorized as 'poor' responders. The average number of variants found was 17,138 per case. The variants were filtered to examine those with predicted moderate or high impacts. Many of the genes with variants had human orthologs with links to cancer, but the majority of variants were not previously reported in canine or human lymphoma. Seven genes had variants found in the cancers of at least two 'poor' responders but in no 'good' responders: ATRNL1, BAIAP2L2, ZNF384, ST6GALNAC5, ENSCAFG00000030179 (human ortholog: riboflavin kinase RFK), ENSCAFG00000029320, and ENSCAFG00000007370 (human ortholog: immunoglobin IGKV4-1). Two genes had variants found in the cancers of at least two 'good' responders but in no 'poor' responders: COX18 and ENSCAFG00000030512. ENSCAFG00000030512 has no reported orthologue in any other species. The role of these mutations in the progression of canine lymphoma requires further functional analyses and larger scale study.


Assuntos
Doenças do Cão/genética , Linfoma de Células B/veterinária , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/genética , Ciclofosfamida/administração & dosagem , Doenças do Cão/tratamento farmacológico , Cães , Doxorrubicina/administração & dosagem , Variação Genética , Estimativa de Kaplan-Meier , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/genética , Prednisolona/administração & dosagem , Resultado do Tratamento , Vincristina/administração & dosagem , Sequenciamento Completo do Genoma
10.
Ann Hematol ; 99(8): 1771-1778, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32601796

RESUMO

Mantle cell lymphoma has a dismal prognosis at relapse or in the refractory setting. Among therapies, mTor pathway targeting by temsirolimus has been the first strategy approved for relapse in Europe. While its efficacy in monotherapy has long been demonstrated, its use remains limited. In the T3 phase Ib clinical trial, we investigated the recommended dose of temsirolimus in association with R-CHOP (R-CHOP-T), or high-dose cytarabine plus rituximab (R-DHA-T), or fludarabine, cyclophosphamide plus rituximab (R-FC-T). From November 11, 2011 to February 26, 2015, forty-one patients were enrolled. Patients presented with high MIPI (47.5%) at relapse and a median number of treatments of 1 (1-3). Patients were treated by R-CHOP-T (n = 10), R-FC-T (n = 14), or R-DHA-T (n = 17) according to the choice of local investigators. The maximum tolerated dose (MTD) was 15 mg in the R-CHOP-T arm and has not been determined in other treatment arms because of toxicities. All patients experienced ≥ Grade 3 adverse events, mainly thrombocytopenia (76%). Twenty-six patients discontinued prematurely the treatment, mostly for toxicity (n = 12) and progression of the disease (n = 8). Of note, 6 patients of the R-DHA-T arm reached complete remission (35%). Temsirolimus with immuno-chemotherapy is associated with a high rate of toxicities. Determination of MTD could only be achieved for R-CHOP-T arm. Associations between temsirolimus and other targeted therapies may be warranted for R/R MCL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoterapia , Linfoma de Célula do Manto/terapia , Sirolimo/análogos & derivados , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente , Trombocitopenia/mortalidade , Vincristina/administração & dosagem , Vincristina/efeitos adversos
11.
Anticancer Res ; 40(7): 3939-3945, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620635

RESUMO

BACKGROUND: Trabectedin and pegylated liposomal doxorubicin (PLD) is an effective combination therapy for platinum-sensitive recurrent ovarian cancer (ROC), particularly for disease relapsing within 6-12 months of platinum therapy. The non-interventional PROSPECTYON study evaluated trabectedin/PLD in French clinical practice. PATIENTS AND METHODS: Patients with ROC after at least one platinum-based regimen received 1.1 mg/m2 trabectedin plus 30 mg/m2 PLD every 3 weeks. Efficacy and safety were evaluated in subgroups according to platinum-free interval [6-12 versus ≥12 months (partially or fully platinum sensitive, respectively)]. RESULTS: Recurrent disease was partially platinum-sensitive in 58 patients and fully sensitive in 33 patients treated between July 2014 and June 2016. Patients in both subgroups received a median of six cycles of trabectedin and PLD. The most common grade 3 or more toxicities were haematological. Median progression-free survival was 6 months for both subgroups. CONCLUSION: Trabectedin/PLD is a valuable treatment option for partially or fully platinum-sensitive ROC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Compostos Organoplatínicos/farmacologia , Polietilenoglicóis/administração & dosagem , Estudos Prospectivos , Trabectedina/administração & dosagem
12.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(1): 20-34, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32621413

RESUMO

Mesenchymal stem cells (MSCs) have the inherent tumor-homing ability with the attraction of multiple chemokines released by tumor tissues or tumor microenvironments, which can be utilized as promising cellular carriers for targeted delivery of anti-tumor drugs and genes. In most circumstances, large amount of systemicly administrated MSCs will be firstly trapped by lungs, following with re-distribution and homing to tumor tissues after lung clearance. Several approaches like enhanced interactions between chemokines and receptors on MSCs or reducing the retention of MSCs by changes of administration methods are firstly reviewed for improving the homing of MSCs towards tumor tissues. Additionally, the potentials and gains of utilizing MSCs to carry several chemotherapeutics, such as doxorubicin, paclitaxel and gemcitabine are summarized, showing the advantages of overcoming the short half-life and poor tumor targeting of these chemotherapeutics. Moreover, the applications of MSCs to protect and deliver therapeutic genes to tumor sites for selectively tumor cells eliminating or promoting immune system are highlighted. In addition, the potentials of using MSCs for tumor-targeting delivery of diagnostic and therapeutic agents are addressed. We believed that the continuous improvement and optimization of this stem cells-based cellular delivery system will provide a novel delivery strategy and option for tumor treatment.


Assuntos
Antineoplásicos , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Células-Tronco Mesenquimais , Neoplasias , Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Neoplasias/terapia , Paclitaxel/administração & dosagem , Pesquisa/tendências
13.
BMJ Case Rep ; 13(7)2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641312

RESUMO

A 17-year-old man with osteosarcoma of the proximal humerus was planned for possible limb salvage surgery after standard neoadjuvant chemotherapy. However, during the surgical phase of treatment, the COVID-19 or SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) outbreak occurred changing the healthcare landscape due to uncertainty regarding the virus, risk of COVID-19 infection and complications, and implementation of an enhanced community quarantine restricting movement of people within cities. Instead of limb salvage surgery, the patient underwent a forequarter amputation. Exposure to the virus in a high-risk hospital setting was minimised with patient discharge after a short hospital stay and home convalescence monitored by video conferencing. Multidisciplinary sarcoma team meetings with family members and a sarcoma navigator nurse were crucial in managing expectations and deciding on appropriate treatment in the setting of a novel infectious disease causing a pandemic.


Assuntos
Amputação/métodos , Neoplasias Ósseas , Cisplatino/administração & dosagem , Infecções por Coronavirus , Doxorrubicina/administração & dosagem , Úmero , Salvamento de Membro/métodos , Osteossarcoma , Pandemias , Pneumonia Viral , Adolescente , Antineoplásicos , Betacoronavirus , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Humanos , Úmero/diagnóstico por imagem , Úmero/cirurgia , Imagem por Ressonância Magnética/métodos , Masculino , Estadiamento de Neoplasias , Osteossarcoma/patologia , Osteossarcoma/terapia , Pandemias/prevenção & controle , Seleção de Pacientes , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle
14.
Life Sci ; 257: 118074, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32673667

RESUMO

AIM: Doxorubicin (DOX) induces dose-dependent cardiotoxicity due to reactive oxygen species (ROS)-mediated oxidative stress and subsequent apoptosis of cardiomyocytes. We aimed to assess whether sodium thiosulfate (STS), which has antioxidant and antiapoptotic properties, exerts cardioprotective effects on DOX-induced cardiomyopathy. MAIN METHODS: Male C57BL/6N mice were divided into four groups, control, DOX, STS, and DOX + STS, and administered DOX (20 or 30 mg/kg) or normal saline intraperitoneally, followed by an injection of STS (2 g/kg) or normal saline 4 h later. KEY FINDINGS: The DOX group showed a poorer 6-day survival and decreased cardiac function than the DOX + STS group. The DOX group showed a marked increase in the plasma creatine kinase isoenzyme myocardial band (CK-MB) and lactate dehydrogenase (LDH) levels 10 h after DOX injection, while the DOX + STS group showed suppression of DOX-induced elevation of CK-MB and LDH levels. The DOX group showed increased 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the heart, whereas the DOX + STS group showed increased catalase and superoxide dismutase (SOD) activities and decreased 8-OHdG levels in the heart compared with DOX group, suggesting that STS reduces DOX-induced DNA damage by improving antioxidant enzymes activities in cardiomyocytes. Additionally, the DOX + STS group showed attenuation of cleaved caspase-3 and DNA fragmentation in cardiomyocytes compared with the DOX group, suggesting that STS suppresses DOX-induced apoptosis in cardiomyocytes. SIGNIFICANCE: STS exerts cardioprotective effects against DOX-induced cardiac dysfunction partly by improving antioxidant defense and suppressing apoptosis, indicating the therapeutic potential of STS against DOX-induced cardiomyopathy.


Assuntos
Cardiotoxicidade/prevenção & controle , Dano ao DNA/efeitos dos fármacos , Doxorrubicina/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Tiossulfatos/farmacologia , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cardiotoxicidade/etiologia , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
15.
J Cancer Res Clin Oncol ; 146(11): 3063-3074, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32617699

RESUMO

PURPOSE: Case reports suggest that ruxolitinib-containing treatment could increase the clinical response rate of patients with hemophagocytic syndrome (HPS). This study aimed to explore the effect of ruxolitinib-containing treatment for patients with lymphoma-associated hemophagocytic syndrome (LAHS). METHODS: This was a retrospective study of patients with LAHS hospitalized at the First Affiliated Hospital of Guangdong Pharmaceutical University between October 2017 and September 2019. Patients were treated with HLH-94 (etoposide and dexamethasone) or R-DED regimen (ruxolitinib, doxorubicin, etoposide, and dexamethasone). The clinical characteristics, treatment responses, and overall survival (OS) were compared. The patients were divided into the HLH-94 group (n = 34) and the R-DED group (n = 36). RESULTS: Compared with HLH-94, R-DED might effectively improve the clinical manifestations, including fever and splenomegaly in patients with LAHS, and control the systemic cytokine storm. The response rate at 2 weeks was 54.8% in the HLH-94 group, which was lower than in the R-DED group (83.3%) (p = 0.011). The OS was significantly prolonged in the R-DED group compared with the HLH-94 group (median, 5 vs. 1.5 months, p = 0.003). The multivariable analysis showed that lower IL-10 levels [hazard ratio (HR)] = 1.000, [95% confidence interval (CI)] 1.000-1.000, p = 0.012), R-DED regimen (HR = 0.196, 95% CI 0.084-0.457, p < 0.001), and non-NK/T-cell lymphoma (HR = 0.254, 95% CI 0.102-0.628, p = 0.003) were associated with better OS. The prognosis of patients with LAHS was generally poor. CONCLUSION: Ruxolitinib can be combined with chemotherapy in HPS. It is feasible, with no early signals of increased toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfo-Histiocitose Hemofagocítica/etiologia , Linfoma/complicações , Linfoma/tratamento farmacológico , Adulto , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Estudos Retrospectivos
16.
Ann Hematol ; 99(10): 2377-2384, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32728938

RESUMO

This study investigated the prognostic value of 25-hydroxy vitamin D (25-(OH)D) deficiency and the association between 25-(OH)D deficiency and c-Myc positivity in 208 newly diagnosed diffuse large B cell lymphoma (DLBCL) patients. 25-(OH)D deficiency was defined as serum 25-(OH)D level lower than 52.5 nmol/L. Using cutoff values of 40%, positive tumor cells for c-Myc expression was established. One hundred forty-two patients had 25-(OH)D deficiency and 70 had c-Myc positivity with a median follow-up of 29 months (range, 16 to 49 months) in this cohort. Multivariate Cox regression analysis showed that 25-(OH)D deficiency was an independent prognostic predictor for inferior progression-free survival (PFS) (P = 0.001) and overall survival (OS) (P = 0.006), and c-Myc positivity was an unfavorable prognostic factor for PFS (P = 0.004). In addition, c-Myc positivity was more frequent in patients with 25-(OH)D deficiency (P = 0.027). Moreover, we found that the presence of c-Myc positivity could aggravate the adverse effects of 25-(OH)D deficiency for PFS time (P = 0.0045). 25-(OH)D deficiency together with IPI (IPI-D) improved the prognostic capacity compared with only IPI in predicting the risk of DLBCL which was assessed by the calculation of receiver operator characteristic (ROC) curves and the areas under the curve (AUC). Noteworthy, c-Myc positivity combined with IPI-D was better than IPI-D in predicting PFS time. In summary, 25-(OH)D deficiency was a strong prognostic factor in DLBCL. Further multi-center prospective studies are needed to confirm the results and better understand the underlying mechanisms.


Assuntos
Genes myc , Linfoma Difuso de Grandes Células B/epidemiologia , Proteínas de Neoplasias/biossíntese , Proteínas Proto-Oncogênicas c-myc/biossíntese , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Área Sob a Curva , China/epidemiologia , Comorbidade , Ciclofosfamida/administração & dosagem , Progressão da Doença , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Prednisona/administração & dosagem , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-myc/genética , Curva ROC , Vincristina/administração & dosagem , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Adulto Jovem
17.
J Vis Exp ; (160)2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32658190

RESUMO

Due to drug resistance and toxicity in healthy cells, use of doxorubicin (DOX) has been limited in clinical cancer therapy. This protocol describes the designing of poly(ethylenimine) grafted with polyethylene glycol (PEI-g-PEG) copolymer functionalized gold nanoparticles (AuNPs) with loaded aptamer (AS1411) and DOX through amide reactions. AS1411 is specifically bonded with targeted nucleolin receptors on cancer cells so that DOX targets cancer cells instead of healthy cells. First, PEG is carboxylated, then grafted to branched PEI to obtain a PEI-g-PEG copolymer, which is confirmed by 1H NMR analysis. Next, PEI-g-PEG copolymer coated gold nanoparticles (PEI-g-PEG@AuNPs) are synthesized, and DOX and AS1411 are covalently bonded to AuNPs gradually via amide reactions. The diameter of the prepared AS1411-g-DOX-g-PEI-g-PEG@AuNPs is ~39.9 nm, with a zeta potential of -29.3 mV, indicating that the nanoparticles are stable in water and cell medium. Cell cytotoxicity assays show that the newly designed DOX loaded AuNPs are able to kill cancer cells (A549). This synthesis demonstrates the delicate arrangement of PEI-g-PEG copolymers, aptamers, and DOX on AuNPs that are achieved by sequential amide reactions. Such aptamer-PEI-g-PEG functionalized AuNPs provide a promising platform for targeted drug delivery in cancer therapy.


Assuntos
Aptâmeros de Nucleotídeos/química , Doxorrubicina/química , Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Ouro/química , Nanopartículas Metálicas/química , Polietilenoglicóis/química , Polietilenoimina/análogos & derivados , Células A549 , Técnicas de Química Sintética , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Humanos , Oligodesoxirribonucleotídeos/química , Polietilenoimina/química
18.
Ann Hematol ; 99(8): 1823-1831, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32577843

RESUMO

Although overall survival in diffuse large B cell lymphomas (DLBCL) has improved, central nervous system (CNS) relapse is still a fatal complication of DLBCL. For this reason, CNS prophylaxis is recommended for patients at high risk of CNS disease. However, no consensus exists on definition of high-risk patient and optimal CNS prophylaxis. Systemic high-dose methotrexate in combination with R-CHOP has been suggested as a potential prophylactic method, since methotrexate penetrates the blood-brain barrier and achieves high concentration in the CNS. In this retrospective analysis, we report treatment outcome of 95 high-risk DLBCL/FL grade 3B patients treated with R-CHOP or its derivatives with (N = 57) or without (N = 38) CNS prophylaxis. At a median follow-up time (51 months), CNS relapses were detected in twelve patients (12.6%). Ten out of twelve (83%) of CNS events were confined to CNS system only. Median overall survival after CNS relapse was 9 months. Five-year isolated CNS relapse rates were 5% in the prophylaxis group and 26% in the group without prophylaxis. These findings suggest that high-dose methotrexate-containing prophylaxis decreases the risk of CNS failure.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/prevenção & controle , Linfoma Difuso de Grandes Células B/prevenção & controle , Metotrexato/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/mortalidade , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Incidência , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Recidiva , Rituximab/administração & dosagem , Vincristina/administração & dosagem
20.
Bone Joint J ; 102-B(6): 795-803, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32475245

RESUMO

AIMS: To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. METHODS: Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson's correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. RESULTS: OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. CONCLUSION: Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795-803.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/cirurgia , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Metotrexato/administração & dosagem , Osteossarcoma/tratamento farmacológico , Osteossarcoma/cirurgia , Adolescente , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Correlação de Dados , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Necrose/induzido quimicamente , Terapia Neoadjuvante , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Período Pré-Operatório , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
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