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1.
Ann Palliat Med ; 10(10): 10575-10583, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763504

RESUMO

BACKGROUND: To analyze the clinical effect of bevacizumab combined with cisplatin in the treatment of malignant pleural effusion and ascites. METHODS: A total of 86 patients with malignant pleural effusion and ascites admitted from June 2018 to September 2020 were selected as the research participants and randomly divided into a control group and observation group, with 43 cases in each group. The control group was given cisplatin intracavitary perfusion scheme, and the observation group was given bevacizumab combined with cisplatin intracavitary perfusion scheme. The Symptom Checklist 90 (SCL-90), Hamilton Depression Scale (HAM-D), and Hamilton Anxiety Scale (HAM-A) were used to evaluate participants' self-perceived negative symptoms, depression, and anxiety. The therapeutic effect and adverse reactions of the 2 groups were compared. The t-test was used for measurement data, and c2 test was used for enumeration data. Statistical significance was considered at P<0.05. RESULTS: After treatment, the serum levels of hypoxia inducible factor-1 (HIF-1α) and vascular endothelial growth factor (VEGF) in the observation group were significantly decreased and statistically lower than those in the control group (both P<0.05); the malignant pleural and abdominal water volume, average urine volume, and average chest circumference of the observation group were improved, and the difference was statistically significant compared with the control group (all P<0.05). The scores of each factor of SCL-90 in the observation group were decreased, among which the scores of somatization, interpersonal sensitivity, depression, anxiety, hostility, and terror in the observation group were significantly lower than those in the control group (all P<0.05); after treatment, the HAMD and HAMA scores of the observation group decreased, and the scores of HAMD (13.71±5.98) and HAMA (17.62±3.98) of the observation group were significantly lower than the score of (16.52±5.75) and (21.54±4.77) of the control group (both P<0.05). CONCLUSIONS: In the clinical treatment of malignant pleural effusion and ascites, bevacizumab combined with cisplatin intracavitary perfusion can improve the clinical treatment effect, reduce the depression and anxiety of patients, optimize patient quality of life, and improve the safety of treatment. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100048959.


Assuntos
Neoplasias Pulmonares , Derrame Pleural Maligno , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ascite/tratamento farmacológico , Ascite/etiologia , Bevacizumab/uso terapêutico , Cisplatino/efeitos adversos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Derrame Pleural Maligno/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular
2.
Otolaryngol Clin North Am ; 54(6): 1101-1115, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34774227

RESUMO

Ototoxicity refers to damage to the inner ear that leads to functional hearing loss or vestibular disorders by selected pharmacotherapeutics as well as a variety of environmental exposures (eg, lead, cadmium, solvents). This article reviews the fundamental mechanisms underlying ototoxicity by clinically relevant, hospital-prescribed medications (ie, aminoglycoside antibiotics or cisplatin, as illustrative examples). Also reviewed are current strategies to prevent prescribed medication-induced ototoxicity, with several clinical or candidate interventional strategies being discussed.


Assuntos
Orelha Interna , Ototoxicidade , Aminoglicosídeos/efeitos adversos , Antibacterianos/efeitos adversos , Cisplatino/efeitos adversos , Humanos
3.
Anticancer Res ; 41(11): 5749-5759, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732448

RESUMO

BACKGROUND/AIM: Systemic immune-inflammation index (SII) predicts survival of patients with various malignancies. This study explored the prognostic value of SII in metastatic urothelial carcinoma (MUC) subjects. PATIENTS AND METHODS: We evaluated 181 consecutive MUC patients treated with first-line platinum-based therapy. Karnofsky performance status <80% and visceral metastasis were present in 18.2% and 46.4% of patients, respectively. SII was based on platelet × neutrophil/lymphocyte counts. Study population was dichotomized by median into high and low SII groups before the initiation of chemotherapy and at week 6. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared with the log-rank test. RESULTS: At median follow-up of 9.6 months, 174 patients experienced disease progression and 173 died. Patients with low SII at baseline and at week 6 had significantly better PFS (HR=0.58; p=0.0002 and HR=0.55; p<0.0001) and OS (HR=0.54; p<0.0001 and HR=0.54; p<0.0001) compared to patients with high SII. Independent prognostic value of SII was confirmed in a multivariate analysis. CONCLUSION: High SII before chemotherapy that persists at week 6 negatively affects survival. SII at baseline can be used in the stratification of patients within clinical trials and in clinical practice.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Plaquetas , Carboplatina/uso terapêutico , Carcinoma/tratamento farmacológico , Cisplatino/uso terapêutico , Linfócitos , Neutrófilos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Urotélio/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Carcinoma/imunologia , Carcinoma/mortalidade , Carcinoma/secundário , Cisplatino/efeitos adversos , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Eslováquia/epidemiologia , Fatores de Tempo , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Urotélio/imunologia , Urotélio/patologia , Adulto Jovem
4.
Oncoimmunology ; 10(1): 1971418, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616588

RESUMO

Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurrent chemoradiotherapy with the anti-PD-1 antibody camrelizumab as first-line treatment for these patients. In this phase 1b study (ClinicalTrials.gov NCT03671265), patients received concurrent chemotherapy (cisplatin [25 mg/m2] plus docetaxel [25 mg/m2] for 4 weeks) and radiotherapy (2.0 Gy/fraction, total 60 Gy) with camrelizumab (200 mg every 2 weeks for 32 weeks). Primary endpoints were safety and tolerability, and health-related quality of life. Secondary endpoints were radiological and pathological response rates, overall survival (OS), and progression-free survival (PFS). Candidate biomarkers in tumor and peripheral blood were monitored at baseline and after 40 Gy radiation. Twenty patients were enrolled. The most common treatment-related grade 3 adverse events included radiation esophagitis (20%) and esophageal fistula (10%). Serious treatment-related adverse events occurred in eight (40%) patients. No treatment-related deaths were reported. Health-related quality of life did not deteriorate. Thirteen (65%) patients had an objective response after 40 Gy radiation. At a median follow-up of 23.7 months (95% CI 21.9-24.5), OS and PFS time ranged from 8.2-28.5 and 4.0-28.5 months, respectively. The 12-month and 24-month OS rate was 85.0% and 69.6%; PFS rate was 80.0% and 65.0%. Tumor PD-L1 expression and CD11c+ dendritic cells and peripheral-blood IL-27, IL-15, Eotaxin-3, and IL-22 were associated with OS. First-line concurrent chemoradiotherapy plus camrelizumab had a manageable safety profile and promising antitumour efficacy for ESCC, and deserves further study.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Docetaxel/uso terapêutico , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Humanos , Qualidade de Vida
5.
BMC Cancer ; 21(1): 1073, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598694

RESUMO

BACKGROUND: This study aimed to evaluate the feasibility, safety, and efficacy of postoperative adjuvant chemotherapy with docetaxel/cisplatin/S-1 (DCS) following S-1 therapy in patients with stage III gastric cancer after curative gastrectomy. METHODS: Patients with stage III gastric cancer who underwent D2 gastrectomy were enrolled. Adjuvant chemotherapy was initiated within 8 weeks of gastrectomy. The first cycle of chemotherapy consisted of S-1 monotherapy (day 1-14), followed by a 7-day rest period. Cycles 2 and 3 consisted of the following: S-1 (day 1-14) administration, followed by a 14-day rest period, and an intravenous infusion of cisplatin and docetaxel on days 1 and 15. After two cycles, S-1 was administered for up to 1 year. RESULTS: Thirty patients were enrolled between 2014 and 2017. Febrile neutropenia of grade 3 or higher was the most common hematological toxicity with 4 patients (13.3%). Other hematological toxicities of grade 3 or higher were as follows: neutropenia in 3 (10.0%), leukopenia in 3 (10.0%), and anemia in 2 (6.7%) patients. Most frequent non-hematological toxicity of grade 3 was anorexia (n = 4, 13.3%) and general fatigue (n = 3, 10.0%); no grade 4 non-hematological toxicities were observed. Twenty-five patients (83.3%) completed two cycles of DCS treatment and 18 (60.0%) completed subsequent S-1 treatment for 1 year. The relative dose intensity of docetaxel and cisplatin was 0.86 and that of S-1 was 0.88. CONCLUSION: The DCS regimen can be acceptable as an adjuvant chemotherapy and offers an effective postoperative treatment option for stage III gastric cancer patients. TRIAL REGISTRATION NUMBER: UMIN000012785 . DATE OF REGISTRY: 08/01/2014.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Anemia/induzido quimicamente , Anorexia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Neutropenia Febril Induzida por Quimioterapia/etiologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Esquema de Medicação , Combinação de Medicamentos , Fadiga/induzido quimicamente , Estudos de Viabilidade , Feminino , Humanos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Cooperação do Paciente , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , Tegafur/efeitos adversos
6.
Braz J Med Biol Res ; 54(12): e11353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34669782

RESUMO

Cisplatin is a widely used chemotherapeutic drug, but its side effects are a major limiting factor. Nephrotoxicity occurs in one third of patients undergoing cisplatin treatment. The acute tubular injury caused by cisplatin often leads to a defective repair process, which translates into chronic renal disorders. In this way, cisplatin affects tubular cells, and maladaptive tubules regeneration will ultimately result in tubulointerstitial fibrosis. Kinins are well known for being important peptides in the regulation of inflammatory stimuli, and kinin B1 receptor deficiency and antagonism have been shown to be beneficial against acute cisplatin nephrotoxicity. This study aimed to analyze the effects of kinin B1 receptor deletion and antagonism against repeated cisplatin-induced chronic renal dysfunction and fibrosis. Both the deletion and the antagonism of B1 receptor exacerbated cisplatin-induced chronic renal dysfunction. Moreover, the inhibition of B1 receptor increased tubular injury and tubulointerstitial fibrosis after repeated treatment with cisplatin. The balance between M1/M2 macrophage polarization plays an important role in renal fibrosis. Kinin B1 receptor antagonism had no impact on M1 markers when compared to cisplatin. However, YM1, an M2 marker and an important molecule for the wound healing process, was decreased in mice treated with kinin B1 receptor antagonist, compared to cisplatin alone. Endothelin-1 levels were also increased in mice with B1 receptor inhibition. This study showed that kinin B1 receptor inhibition exacerbated cisplatin-induced chronic renal dysfunction and fibrosis, associated with reduced YM1 M2 marker expression, thus possibly affecting the wound healing process.


Assuntos
Injúria Renal Aguda , Preparações Farmacêuticas , Injúria Renal Aguda/induzido quimicamente , Animais , Cisplatino/efeitos adversos , Fibrose , Humanos , Cininas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
7.
In Vivo ; 35(6): 3391-3399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34697174

RESUMO

BACKGROUND/AIM: Cisplatin with 5-fluouracil (Cis/5Fu) and paclitaxel with carboplatin (Pac/Car) are common regimens used in concurrent chemoradiotherapy (CCRT) for patients with locally advanced esophageal cancer (EC). Here, we aimed to compare the survival outcomes and treatment-related toxicities between these regimens in neoadjuvant CCRT in patients with locally advanced EC. PATIENTS AND METHODS: One hundred and thirty-six patients with locally advanced EC (98% squamous cell carcinoma) were prospectively recruited between 2016 and 2017 in a non-randomized manner. Patients were categorized into two groups according to the chemotherapeutic agents administered (Pac/Car group, n=87; Cis/5Fu group, n=47) in CCRT to compare the survival outcome and severe adverse event (sAE) incidence. RESULTS: Forty-two patients (85.7%) and 80 patients (91.4%) in the Cis/5Fu and Pac/Car groups completed pre-planned CCRT (p=0.26), respectively. The Cis/5Fu group presented a higher incidence of non-hematological sAE than the Pac/Car group (69.45% vs. 51.7%, p=0.049). Patients in the Pac/Car group showed a higher rate of surgical resection than those in the Cis/5Fu group (49.4% vs. 22.4%, p<0.001). After a median follow-up duration of 22.0 months (range=1.9-31.8), the 2-year survival rate was 56.9% for patients in the Pac/Car group and 28.7% for the Cis/5Fu group. The hazard ratio (HR) of overall survival was 0.45 (95%CI=0.28-0.72, p=0.001) in the comparison between the groups. CONCLUSION: Overall, neoadjuvant CCRT with Pac/Car is associated with a better survival outcome, higher surgical resection rate, and better safety profiles than Cis/5Fu in patients with locally advanced EC.


Assuntos
Cisplatino , Neoplasias Esofágicas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Fluoruracila/efeitos adversos , Humanos , Paclitaxel/efeitos adversos , Estudos Retrospectivos
8.
Int J Mol Sci ; 22(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34639002

RESUMO

Renal toxicity is a serious side effect that hinders the use of cisplatin, a commonly used and effective chemotherapeutic agent. Meanwhile, quinacrine is an FDA approved drug that has been stated for its anti-inflammatory effect. Thus, we investigated the ameliorative effect of quinacrine against cisplatin-induced renal toxicity. Single intraperitoneal (i.p.) 10 mg/kg cisplatin administration induced renal injury in rats. Our results showed that 10 mg/kg/day quinacrine decreased the mortality rate of rats from 46.15% (cisplatin group) to 12.5%, and significantly decreased renal tissue fibrosis, relative kidney to body weight ratio, serum creatinine and urea levels compared with the cisplatin group. Indeed, quinacrine significantly decreased renal malondialdehyde concentration and increased renal total antioxidant capacity, compared with the cisplatin group. Furthermore, quinacrine caused significant upregulation of renal sirtuin-1 (SIRT-1) with significant downregulation of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α). Moreover, quinacrine significantly blocked cisplatin-induced apoptosis, which was made evident by downregulating renal apoptotic proteins (BAX and p53) and upregulating the renal anti-apoptotic protein BCL2, compared with the cisplatin group. In conclusion, this study demonstrates, for the first time, that quinacrine alleviates cisplatin-induced renal toxicity via upregulating SIRT-1, downregulating inflammatory markers (ICAM-1 and TNF-α), reducing oxidative stress, and inhibiting apoptosis.


Assuntos
Cisplatino/efeitos adversos , Nefropatias/etiologia , Nefropatias/metabolismo , Quinacrina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Fibrose , Imuno-Histoquímica , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/diagnóstico , Nefropatias/tratamento farmacológico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos
9.
An Pediatr (Engl Ed) ; 95(5): 290-297, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34702687

RESUMO

INTRODUCTION: Ototoxicity occurs in different percentages in patients after treatment with platinum-based chemotherapy or cranial radiation therapy. The aim of this study was to present our experience in ototoxicity monitoring. MATERIAL AND METHODS: A review was made of the registry of paediatric cancer patients referred to the Children's Hearing Loss Unit from 1999 to 2019. RESULTS: Of the 46 patients referred to this unit, 41 had received platinum as part of their treatment, 17 patients underwent neurosurgery, and 18 patients received cranial radiation therapy. An anamnesis and otoscopy were performed on all of them, and the monitoring was carried out with tone-verbal audiometry and/or distortion products. Hearing loss was observed in eight patients (21.05% of patients referred for audiological follow-up) as a consequence of the treatment. It was impossible to determine the audiological situation in eight patients at the end of treatment. Hearing aid adaption was necessary in two patients. In coordination with Paediatric Oncology, a change from cisplatin to carboplatin due to bilateral grade two ototoxicity was considered appropriate during treatment in one patient. CONCLUSION: Adequate coordination with Paediatric Oncology is essential to carry out active surveillance for ototoxicity and to modify, if possible, the dosage or type of chemotherapy in case hearing is affected. In our experience, and following current recommendations, a pre-treatment assessment is usually performed, as well as monitoring during treatment, at the end of treatment, and annually thereafter due to the risk of a later development of hearing loss.


Assuntos
Antineoplásicos , Sobreviventes de Câncer , Neoplasias , Ototoxicidade , Antineoplásicos/efeitos adversos , Carboplatina , Criança , Cisplatino/efeitos adversos , Humanos , Neoplasias/tratamento farmacológico
10.
Medicine (Baltimore) ; 100(42): e27475, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34678878

RESUMO

PURPOSE: In recent years, docetaxel, cisplatin, and fluorouracil (TPF)-based induction chemotherapy plus concurrent chemoradiotherapy (CCRT) has been commonly applied for locally advanced nasopharyngeal carcinoma (LA-NPC). However, whether TPF+CCRT regimen is the best choice for LA-NPC remains unclear. This meta-analysis aims to elucidate and compare the efficacy and toxicity of TPF+CCRT versus CCRT alone for LA-NPC. METHODS: Two investigators independently and systematically searched relevant studies available on PubMed, Embase, Cochrane Library, and Web of Science published before January 7, 2021. Data were extracted from eligible studies for assessing their qualities, and calculating pooled hazard ratios (HR), odds ratio (OR) and 95% confidence intervals (CI) using Review Manager software 5.3 (RevMan 5.3). RESULTS: Five studies involving 759 LA-NPC patients were analyzed in the meta-analysis. Compared to CCRT alone, TPF-based IC plus CCRT significantly improved overall survival (OS) (HR = 0.53, 95% CI: 0.35-0.81, P = .003), progression-free survival (PFS) (HR = 0.63, 95% CI: 0.46-0.86, P = .004), distant metastasis-free survival (DMFS) (HR = 0.58, 95% CI: 0.39-0.86, P = .008), and locoregional failure-free survival (LRFFS) (HR 0.62, 95% CI: 0.43-0.90, P = .01). In addition, TPF-based IC plus CCRT mainly increased risks of grade 3/4 acute hematological toxicity and non-hematological toxicities like leukopenia (OR = 1.84, 95% CI: 0.42-8.03, P = .42), neutropenia (OR = 1.78, 95% CI: 0.23-13.82, P = .58), thrombocytopenia (OR = 1.76, 95% CI: 0.53-5.81, P = .35), febrile neutropenia (OR = 2.76, 95% CI: 0.07-101.89, P = .58), vomiting (OR = 18.94, 95% CI: 0.99-362.02, P = .05) and dry mouth (OR = 2.23, 95% CI: 0.22-22.57, P = .50), which were uncomplicated and manageable. CONCLUSIONS: TPF + CCRT is superb than CCRT alone for the management of LA-NPC. However, TPF+CCRT increases the incidences of grade 3/4 acute hematological toxicity and some non-hematological toxicities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Quimioterapia de Indução/métodos , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Estudos Observacionais como Assunto , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxoides/efeitos adversos , Taxoides/uso terapêutico
11.
ESMO Open ; 6(5): 100277, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34626918

RESUMO

BACKGROUND: Oral mucositis (OM) is an unpleasant adverse event in patients receiving chemotherapy. A prospective feasibility study showed that elemental diet (ED), an oral supplement that does not require digestion, may prevent OM. Based on this, we established a central review system for oral cavity assessment by dental oncology specialists blinded to background data. We used this system to elucidate the preventive effect of an ED against OM in patients with esophageal cancer receiving docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy. PATIENTS AND METHODS: In this phase III, multicenter, parallel-group, controlled trial, patients consuming a normal diet orally were randomly assigned (1 : 1) to receive two cycles of DCF with (group A) or without (group B) an ED (Elental® 160 g/day). We assessed the incidence of grade ≥2 OM evaluated by two reviewers, changes in body weight, prealbumin, C-reactive protein, and DCF completion rate based on ED compliance. RESULTS: Of the 117 patients randomly assigned to treatment, four failed to start treatment and were excluded from the primary analysis; thus, groups A and B comprised 55 and 58 patients, respectively. There were no significant differences in background characteristics. Grade ≥2 OM was observed in eight (15%) and 20 (34%) patients in groups A and B, respectively (P = 0.0141). Changes in body weight and prealbumin during the two DCF cycles were significantly higher in group A than B (P = 0.0022 and 0.0203, respectively). During the first cycle, changes in C-reactive protein were significantly lower in group A than B (P = 0.0338). In group A (receiving ED), the DCF completion rate was 100% in patients with 100% ED compliance and 70% in patients failing ED completion (P = 0.0046). CONCLUSIONS: The study findings demonstrate that an ED can prevent OM in patients with esophageal cancer receiving chemotherapy.


Assuntos
Cisplatino , Neoplasias Esofágicas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Docetaxel/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Fluoruracila/efeitos adversos , Alimentos Formulados , Humanos , Estudos Prospectivos
12.
World J Surg Oncol ; 19(1): 280, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535176

RESUMO

BACKGROUND: This study was designed to probe into the effect of cisplatin combined with capecitabine on nasopharyngeal carcinoma (NPC). METHODS: A total of 136 NPC patients treated for the first time in our hospital from January 2016 to March 2017 were collected and divided into two groups: A and B. Among them, 66 in group A were treated with cisplatin intravenous drip, while 70 in group B were treated with capecitabine on the basis of group A. The efficacy, toxic and side effects, and quality of life of the two groups were observed. RESULTS: The short-term efficacy of group B was better than that of group A (p<0.05). The toxic and side effects of group B were lower than that of group A (p<0.05). The quality of life in group B was higher than that in group A (p<0.05). CONCLUSIONS: Cisplatin combined with capecitabine-induced chemotherapy for local NPC can improve the quality of life and reduce the toxic and side effects.


Assuntos
Cisplatino , Neoplasias Nasofaríngeas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Quimiorradioterapia , Cisplatino/efeitos adversos , Fluoruracila/efeitos adversos , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Prognóstico , Qualidade de Vida
13.
Int J Clin Oncol ; 26(12): 2275-2281, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34468885

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive disease that is often diagnosed at an advanced stage. There is no standard treatment for metastatic ACC; EDP-M (etoposide, doxorubicin, and cisplatin plus mitotane) is one treatment option. A randomized controlled trial (FIRM-ACT) evaluating the efficacy of EDP-M showed progression-free survival (PFS) was 5.0 months, overall survival (OS) was 14.8 months, the response rate was 19%, and adrenal insufficiency occurred in 3.4% of patients. However, the efficacy and safety of this regimen in Asia are not fully reported. METHODS: We retrospectively analyzed 43 patients diagnosed with metastatic ACC at the National Cancer Center Hospital between 1997 and 2020. We evaluated PFS, OS, and response in 17 patients who received EDP-M as first-line therapy. RESULTS: The median age at treatment initiation was 45 years (range 18-74). Eight patients (47%) had autonomous hormone production, including six patients with hypercortisolism. The best response of partial response and stable disease was seen in two (12%) and ten (59%) patients, respectively. The median PFS was 6.2 months [95% confidence interval (CI): 4.3-10.0]. The median OS was 15.4 months (95% CI 11.6-not reached). Three patients received only one cycle due to adverse effects associated with hypercortisolism. Grade 3/4 adverse events associated with adrenal insufficiency occurred in three (17%) cases, resulting in EDP-M discontinuation. CONCLUSIONS: The EDP-M regimen had similar PFS to that observed in FIRM-ACT. Adrenal insufficiency was more frequent in the current study, but this could be managed with supportive endocrinological care such as cortisol replacement.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Adolescente , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Doxorrubicina/efeitos adversos , Etoposídeo/efeitos adversos , Humanos , Pessoa de Meia-Idade , Mitotano/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
ESMO Open ; 6(5): 100249, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34482181

RESUMO

BACKGROUND: Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. We assessed the efficacy and tolerability of pemetrexed and cisplatin combination therapy in patients with refractory bone and soft tissue sarcoma (STS). PATIENTS AND METHODS: Patients were included in this multicenter, phase II study (ClinicalTrials.gov identifier NCT03809637) if they progressed after receiving one or more chemotherapy regimens containing an anthracycline and/or ifosfamide. Pemetrexed was first administered intravenously, followed by cisplatin, over a cycle of 21 days, for a maximum of six cycles. The primary endpoint was a progression-free rate (PFR) at 3 months (3-month PFR). RESULTS: From January 2017 to September 2019, we enrolled 37 patients; of these, 73% had previously undergone three or more rounds of chemotherapy. Five patients (13.5%) exhibited objective responses, including two patients (2/6, 33.3%) with malignant peripheral nerve sheath tumors, one patient (1/4, 25%) with synovial sarcoma, one patient (1/4, 25%) with undifferentiated pleomorphic sarcoma, and one patient (1/4, 25%) with angiosarcoma. The median progression-free survival was 2.6 months, and the 3-month PFR was 45.9% (n = 17). None of the four patients with osteosarcoma exhibited objective responses or were progression free at 3 months. The most frequent treatment-related grade 3-4 toxicities included neutropenia (16.2%), anemia (13.5%), thrombocytopenia (13.5%), and fatigue (8.1%). Among 26 patients (70.3%) available for immunohistochemical assessments, patients in the low-excision repair cross-complementation group 1 (ERCC1) and low-thymidylate synthase expression groups showed a tendency for longer overall survival. CONCLUSIONS: Combination therapy with pemetrexed and cisplatin was associated with clinically meaningful and sustained responses among patients with advanced and refractory STS. The combination therapy met its predefined primary study endpoint.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Cisplatino/efeitos adversos , Humanos , Ifosfamida , Pemetrexede/efeitos adversos , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico
15.
Am J Audiol ; 30(3S): 870-886, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34582263

RESUMO

Purpose Determine the efficacy of ototoxicity monitoring (OM) administered as automated protocols with the Oto-ID mobile audiometer (automated ototoxicity monitoring [A-OM]), compared with usual care (UC) OM in cancer patients receiving cisplatin. Method Participants were patients (n = 46, mean age 64.7 years; range: 30-78 years) receiving cisplatin-based chemotherapy at the Department of Veterans Affairs Portland Health Care System. A randomized controlled trial contrasted A-OM and UC at up to three program evaluations (PEs) conducted by the study audiologist who was blinded to arm through PE1. PE1 occurred before randomization or oncology treatment; PE2 and PE3 occurred during and/or after treatment at 35 and 365 days postrandomization. The A-OM group (n = 24) used Oto-ID to screen their hearing before each cisplatin dose. Oto-ID results were sent to the study audiologist for interpretation, follow-up, and care coordination. The UC group (n = 22) received a consult for OM services through the audiology clinic. Outcomes included hearing shift near each patient's high-frequency hearing limit, revised hearing-handicap inventory score, and survival time from the start of treatment. Adherence to OM protocols, patients' use of aural rehabilitation services, and oncologists' treatment decisions were also examined. Results Ototoxicity was identified at a high overall rate (46% and 76% at 35 and 365 days, respectively, postrandomization). Adherence to monitoring prior to each cisplatin dose was 83.3% for those randomized to A-OM compared with 4.5% for UC. Randomization to A-OM was not associated with reduced ototoxic hearing shifts or self-reported hearing handicap relative to UC; neither did it compromise participants' survival. Half of participants in each arm accessed aural rehabilitation services. One in each arm had a documented ototoxicity-related cisplatin dose reduction. Conclusions Auditory impairment was an actionable concern for the participants and their oncology providers. A dedicated surveillance program using the Oto-ID's automated protocols improved adherence to OM recommendations over a traditional UC service delivery model. Supplemental Material https://doi.org/10.23641/asha.16649602.


Assuntos
Perda Auditiva , Neoplasias , Ototoxicidade , Cisplatino/efeitos adversos , Perda Auditiva/induzido quimicamente , Perda Auditiva/diagnóstico , Humanos , Pessoa de Meia-Idade , Tecnologia
16.
Gan To Kagaku Ryoho ; 48(8): 1037-1042, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34404072

RESUMO

BACKGROUND: Cisplatin that is used in the treatment of gastric cancer not only has gastrointestinal side effects but also has a high serum protein-bound fraction. Reduction of serum albumin concentration may cause increase the risk of cisplatin- induced neutropenia. Hence, alteration of serum albumin concentration poses a major safety issue during anticancer therapy. METHODS: For gastric cancer patients who received cisplatin plus S-1 therapy, we investigated the relationship between the serum albumin concentration before cisplatin administration in the treatment course during which the neutrophil count reached nadir and the neutrophil count fluctuation after cisplatin administration. RESULTS: In the grade 3-4 neutropenia and grade 0-2 neutropenia groups, the mean serum albumin concentration before cisplatin administration was 3.39±0.60 and 3.85±0.59 g/dL, respectively; in the former group were significantly lower than in the latter group(p=0.006). Lower serum albumin concentrations before cisplatin administration were significantly correlated with a decrease in neutrophil count after cisplatin administration(r=0.463, p<0.001). According to the receiver operating characteristic curve analysis, patients with serum albumin concentrations below 3.25 g/dL before cisplatin administration exhibited a significantly higher incidence of grade 3-4 neutropenia(odds ratio: 4.33). CONCLUSIONS: Decreased serum albumin levels were found to be strongly associated with the prediction of the development of severe neutropenia. Our findings emphasize serum albumin concentration needs to be evaluated before each administration of cisplatin.


Assuntos
Neutropenia , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Humanos , Neutropenia/induzido quimicamente , Estudos Retrospectivos , Albumina Sérica , Neoplasias Gástricas/tratamento farmacológico
17.
Medicine (Baltimore) ; 100(32): e26845, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397891

RESUMO

RATIONALE: Despite the development of human papillomavirus vaccines and significant improvement in cervical cancer screening over the past few years, cervical cancer remains the fourth most common cancer in women of childbearing age after breast cancer, melanoma, and thyroid cancer. PATIENT CONCERNS: In this case report, the patients are all cervical cancer with stage IB2 and IB3 during pregnancy, the management constitutes a major medical challenge related to the impact of treatment on both maternal and fetal outcomes. Neoadjuvant chemotherapy (NACT) is an innovative option for cervical cancer patients with stage IB2 and IB3 before cesarean delivery and radical hysterectomy, and many chemotherapeutic agents are available, cisplatin plus paclitaxel yielded good maternal and fetal outcomes to the authors' knowledge. DIAGNOSES: Masses were discovered in the cervix of 4 pregnant women with a history of vaginal bleeding. Biopsy examination of the masses revealed cervical carcinoma, which was staged in accordance with the International Federation of Gynecology and Obstetrics (i.e., FIGO) system. INTERVENTIONS: The patients were treated with paclitaxel plus cisplatin, followed by cesarean delivery and radical hysterectomy. OUTCOMES: The 4 patients were treated successfully, with no recurrence during follow-up periods of 14 to 56 months, and all of the children were doing well with no anomalies. LESSONS: Although further data are required, in pregnant women with invasive cervical cancer, NACT with cisplatin plus paclitaxel followed by cesarean delivery and radical hysterectomy was a practical treatment option.


Assuntos
Cisplatino , Histerectomia/métodos , Paclitaxel , Complicações Neoplásicas na Gravidez , Neoplasias do Colo do Útero , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biópsia/métodos , Colo do Útero/patologia , Cesárea/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/cirurgia , Resultado da Gravidez , Resultado do Tratamento , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
18.
Nat Med ; 27(9): 1536-1543, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34341578

RESUMO

Gemcitabine-cisplatin (GP) chemotherapy is the standard first-line systemic treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). In this international, double-blind, phase 3 trial (ClinicalTrials.gov identifier: NCT03581786), 289 patients with RM-NPC and no previous chemotherapy for recurrent or metastatic disease were randomized (1/1) to receive either toripalimab, a monoclonal antibody against human programmed death-1 (PD-1), or placebo in combination with GP every 3 weeks for up to six cycles, followed by monotherapy with toripalimab or placebo. The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee according to RECIST v.1.1. At the prespecified interim PFS analysis, a significant improvement in PFS was detected in the toripalimab arm compared to the placebo arm: median PFS of 11.7 versus 8.0 months, hazard ratio (HR) = 0.52 (95% confidence interval (CI): 0.36-0.74), P = 0.0003. An improvement in PFS was observed across key subgroups, including PD-L1 expression. As of 18 February 2021, a 40% reduction in risk of death was observed in the toripalimab arm compared to the placebo arm (HR = 0.603 (95% CI: 0.364-0.997)). The incidence of grade ≥3 adverse events (AEs) (89.0 versus 89.5%), AEs leading to discontinuation of toripalimab/placebo (7.5 versus 4.9%) and fatal AEs (2.7 versus 2.8%) was similar between the two arms; however, immune-related AEs (39.7 versus 18.9%) and grade ≥3 infusion reactions (7.5 versus 0.7%) were more frequent in the toripalimab arm. In conclusion, the addition of toripalimab to GP chemotherapy as a first-line treatment for patients with RM-NPC provided superior PFS compared to GP alone, and with a manageable safety profile.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/patologia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão
19.
In Vivo ; 35(5): 2821-2829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410974

RESUMO

BACKGROUND/AIM: Standard chemotherapy for advanced urothelial carcinoma (UC) patients with moderate renal dysfunction has not yet been established. PATIENTS AND METHODS: We retrospectively assessed outcomes of patients with advanced UC who underwent first-line chemotherapy with full-/reduced-dose gemcitabine plus cisplatin (GC-f/GC-r) or full-/reduced-dose gemcitabine plus carboplatin (G-Car-f/G-Car-r) according to renal function. RESULTS: Seventy-eight patients were included in this study. The objective response rate was 42%, 30%, 42%, and 27% for the GC-f, GC-r, G-Car-f, and G-Car-r groups, respectively. For the GC-r and G-Car-f groups, the median progression-free survival and the median overall survival was 4.5 vs. 7.0 months (p=0.07) and 7.5 months vs. 12.0 months (p=0.124), respectively. Grade 3/4 thrombocytopenia occurred more frequently in the GC-r group than the G-Car-f group (80% vs. 38%, p=0.021). CONCLUSION: G-Car-f could be more beneficial than GC-r for patients with advanced UC who have moderate renal dysfunction.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/efeitos adversos , Humanos , Rim/fisiologia , Platina , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico
20.
Dokl Biochem Biophys ; 499(1): 282-288, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34426927

RESUMO

The present study investigated Dioscorea deltoidea leaf extract (DDLE) for treatment of cisplatin-induced ovarian injury in rat model. DDLE treatment of the cisplatin-induced ovarian injury rats suppressed Follicle-stimulating hormone (FSH) release and promoted the estrogen E2 level in serum samples. Development of follicles was increased while as damage to ovarian cortex on day 14, 28, and 42 was inhibited in cisplatin-induced ovarian injury rats on treatment with DDLE. In cisplatin-induced ovarian injury rat model oxidative stress showed a significant increase because of reduction in the level of antioxidant enzyme activity. However, DDLE treatment led to a prominent increase in activity of antioxidant enzyme compared to the control group. Moreover, DDLE treatment regulated the expression of Nuclear factor erythroid 2-related factor 2 protein in cisplatin-induced ovarian injury rats. In conclusion, DDLE treatment prevents cisplatin-induced ovarian injury through inhibition of malondialdehyde (MDA) level and upregulation of superoxide dismutase (SOD) and catalase (CAT) activity.


Assuntos
Cisplatino/efeitos adversos , Dioscorea/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Rim/efeitos dos fármacos , Rim/metabolismo , Malondialdeído/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo
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