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1.
Anticancer Res ; 42(1): 363-371, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34969746

RESUMO

BACKGROUND/AIM: To evaluate the clinical desire for pressurized intraperitoneal aerosol chemotherapy (PIPAC) in South Korea. PATIENTS AND METHODS: We performed an online survey on surgical oncologists between November and December 2019 using a questionnaire consisting of 20 questions. RESULTS: A total of 164 respondents answered the questionnaire. Among those specialized in ovarian cancer, pseudomyxoma peritonei, and malignant mesothelioma 41.7-50% preferred PIPAC for the curative treatment of primary diseases, whereas 32.7-33.3% majoring in colorectal and hepatobiliary cancers chose it for the palliative treatment of recurrent diseases. Furthermore, 66.7-95.2% considered PIPAC appropriate for the cancers they specialized in, and 76-78.7% expected a treatment response of more than 50% and considered grade 1 or 2 complications acceptable. Most respondents answered the reasonable costs to purchase and implement PIPAC once at between 1,000,000-5,000,000 South Korean Won (KRW). CONCLUSION: Most Korean surgical oncologists expected relatively high tumor response rates with minor toxicities through the repeated implementation of PIPAC.


Assuntos
Infusões Parenterais/métodos , Mesotelioma Maligno/cirurgia , Oncologistas/psicologia , Neoplasias Ovarianas/cirurgia , Pseudomixoma Peritoneal/cirurgia , Aerossóis/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Custos e Análise de Custo , Doxorrubicina/uso terapêutico , Feminino , Humanos , Masculino , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma Maligno/patologia , Metástase Neoplásica , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Oxaliplatina/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/tratamento farmacológico , Pseudomixoma Peritoneal/patologia , Inquéritos e Questionários , Resultado do Tratamento
2.
Anticancer Res ; 42(1): 185-193, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34969724

RESUMO

BACKGROUND: We hypothesized that perioperative FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) might be used as an alternative to standard FLOT (docetaxel, 5-fluorouracil, leucovorin, and oxaliplatin) in patients with locally advanced oesogastric adenocarcinomas (OGA), particularly those with frailties. PATIENTS AND METHODS: We reviewed the charts of 61 consecutives patients treated with FOLFOX for resectable OGA to estimate overall survival, recurrence-free survival, and safety. RESULTS: The median follow-up was 69.7 (range=3.6-97.9) months. Few patients experienced grade 3 adverse events during the preoperative (n=6; 10%) and postoperative (n=6; 16%) phases. One patient experienced a fatal grade 5 adverse events (cardiogenic shock). Median overall survival was 51.7 months [95% confidence interval (CI)=31.6-93.2 months] and the 5-year survival rate was 44.4% (95% CI=30.3%-57.5%). CONCLUSION: Regarding its comparable efficacy and its favourable toxicity profile, perioperative FOLFOX is a reasonable alternative to FLOT for frail patients with resectable OGA.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Junção Esofagogástrica/efeitos dos fármacos , Junção Esofagogástrica/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Período Perioperatório , Modelos de Riscos Proporcionais , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia
3.
Int J Cancer ; 150(2): 335-346, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34520572

RESUMO

The impact of cycle completion rates of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer in real-world practice is unknown. We assessed its impact, and that of treatment modification, on 3-year cancer-specific mortality. Four thousand one hundred and forty-seven patients with pathological stage III colon cancer undergoing major resection from 2014 to 2017 in the English National Health Service were included. Chemotherapy data came from linked national administrative datasets. Competing risk regression analysis for 3-year cancer-specific mortality was performed according to completion of <6, 6-11, or 12 5-fluoropyrimidine and oxaliplatin (FOLFOX) cycles, or <4, 4-7, or 8 capecitabine and oxaliplatin (CAPOX) cycles, adjusted for patient, tumour and hospital-level characteristics. Median age was 64 years. Thirty-two per cent of patients had at least one comorbidity. Forty-two per cent of patients had T4 disease, and 40% had N2 disease. Compared to completion of 12 FOLFOX cycles, cancer-specific mortality was higher in patients completing <6 cycles [subdistribution hazard ratios (sHR) 2.17; 95% CI 1.56-3.03] or 6-11 cycles (sHR 1.40; 95% CI 1.09-1.78) (P < .001). Compared to completion of 8 CAPOX cycles, cancer-specific mortality was higher in patients completing <4 cycles (sHR 2.02; 95% CI 1.53-2.67) or 4-7 cycles (sHR 1.63; 95% CI 1.27-2.10) (P < .001). Dose reduction and early oxaliplatin discontinuation did not impact mortality in patients completing all cycles. Completion of all cycles of chemotherapy was associated with improved cancer-specific survival in real-world practice. Poor prognostic factors may have affected findings, however, patients completing <50% of cycles had poor outcomes. Clinicians may wish to facilitate completion with treatment modification in those able to tolerate it.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/mortalidade , Neoplasias do Colo/mortalidade , Idoso , Idoso de 80 Anos ou mais , Capecitabina/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina/administração & dosagem , Estudos Prospectivos , Taxa de Sobrevida
4.
Support Care Cancer ; 30(1): 33-47, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34410459

RESUMO

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is the most common dose-limiting side effect of oxaliplatin. It often persists and can adversely affect quality of life of colorectal cancer (CRC) survivors. This systematic review explored the proportions of patients with persistent CIPN and the reporting methods used. METHODS: MEDLINE, EMBASE, Web of Science and CINAHL were searched up to March 2021 for publications reporting CIPN outcomes following adjuvant oxaliplatin-containing chemotherapy at prespecified timepoints in participants with CRC. Secondary outcomes assessed the tools used to measure CIPN. Two authors reviewed full text publications for eligibility, data extraction and appraisal. Meta-analysis was performed where Common Terminology Criteria for Adverse Events (any grade) was reported at the most frequent timepoints. RESULTS: From 7895 citations identified, 27 studies met the eligibility criteria: six were randomised control trials, and 21 were non-randomised studies. Pooled prevalence of CIPN at 6, 12, 24 and 36 months after chemotherapy were 58%, 45%, 32% and 24% respectively. The average prevalence of CIPN decreased by 26% per year after chemotherapy (pooled RR = 0.74; 95% CI 0.72-0.75). Across all studies, ten separate tools were used as the primary measure of CIPN. Quality appraisal identified open-label design and inadequate reporting of participants lost to follow-up as the main methodological limitations. CONCLUSION: Our summary of reported rates of persistent CIPN indicates substantial long-term toxicity affecting CRC survivors, and will help clinicians estimate CIPN risk and its change over time. The heterogeneity of CIPN measures identified in the review highlights the need for a standardised CIPN assessment.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Doenças do Sistema Nervoso Periférico , Antineoplásicos/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Humanos , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/epidemiologia , Qualidade de Vida
5.
Talanta ; 237: 122915, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736651

RESUMO

Mass Spectrometry Imaging is an effective technology that allows to determine the in-situ distribution of endogen and/or exogen small molecules. It is a rapidly emerging approach for visualizing drugs and their metabolites within biological tissues. Matrix-Assisted Laser Desorption Ionization (MALDI) Mass Spectrometry Imaging (MSI) coupled to high resolving power analyzer (e.g. TOF) was already investigated for metallodrug localization and metabolization studies, but was proved to suffer from a lack of sensitivity and resolution, leading to poor coverage and assignment. To counter these technological limitations, the use of ultra-high resolving power analyzer such as Fourier Transform Ion Cyclotron Resonance (FTICR) could be revealed as a technique of choice. The high field FTICR MS provides ultra-high resolving power and mass accuracy that allows exhaustive molecule coverage and non-ambiguous molecular formula assignments. Platinum derivatives, such as oxaliplatin, are widely used as therapeutic agents for cancer treatment. The assessment of their intake, distribution and metabolism within the organs is important to know the risks associated with their use. In this study, MALDI FTICR MSI analyses were performed to better understand the penetration and metabolization of platinum derivatives in ovaries of women treated by Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for peritoneal metastasis of colorectal or appendicular origin. Twelve ovary sections, from six ovary samples in six women donors, before and after treatment, were analyzed with 120 µm spatial resolution. For the first time, the high resolving power (220,000 at m/z 457) and sub-ppm accuracy (<1 ppm) of the FTICR combined with an Isotopic Fine Structure study enabled to distinguish two Pt-isobaric species derived from oxaliplatin in biological tissues. One of these, which is unknown, was specifically localized at the contour of the ovary.


Assuntos
Ciclotrons , Lasers , Análise de Fourier , Humanos , Oxaliplatina , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
6.
Chem Biol Interact ; 352: 109772, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-34896366

RESUMO

In the present study it was hypothesized that 5-((4-methoxyphenyl)thio)benzo[c][1,2,5] thiodiazole (MTDZ), a new acetylcholinesterase inhibitor, exerts antinociceptive action and reduces the oxaliplatin (OXA)-induced peripheral neuropathy and its comorbidities (anxiety and cognitive deficits). Indeed, the acute antinociceptive activity of MTDZ (1 and 10 mg/kg; per oral route) was observed for the first time in male Swiss mice in formalin and hot plate tests and on mechanical withdrawal threshold induced by Complete Freund's Adjuvant (CFA). To evaluate the MTDZ effect on OXA-induced peripheral neuropathy and its comorbidities, male and female Swiss mice received OXA (10 mg/kg) or vehicle intraperitoneally, on days 0 and 2 of the experimental protocol. Oral administration of MTDZ (1 mg/kg) or vehicle was performed on days 2-14. OXA caused cognitive impairment, anxious-like behaviour, mechanical and thermal hypersensitivity in animals, with females more susceptible to thermal sensitivity. MTDZ reversed the hypersensitivity, cognitive impairment and anxious-like behaviour induced by OXA. Here, the negative correlation between the paw withdrawal threshold caused by OXA and acetylcholinesterase (AChE) activity was demonstrated in the cortex, hippocampus, and spinal cord. OXA inhibited the activity of total ATPase, Na+ K+ - ATPase, Ca2+ - ATPase and altered Mg2+ - ATPase in the cortex, hippocampus, and spinal cord. OXA exposure increased reactive species (RS) levels and superoxide dismutase (SOD) activity in the cortex, hippocampus, and spinal cord. MTDZ modulated ion pumps and reduced the oxidative stress induced by OXA. In conclusion, MTDZ is an antinociceptive molecule promising to treat OXA-induced neurotoxicity since it reduced nociceptive and anxious-like behaviours, and cognitive deficit in male and female mice.


Assuntos
Inibidores da Colinesterase/uso terapêutico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/enzimologia , Tiadiazóis/uso terapêutico , Adenosina Trifosfatases/metabolismo , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Inibidores da Colinesterase/química , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Masculino , Camundongos , Oxaliplatina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Medula Espinal/efeitos dos fármacos , Medula Espinal/enzimologia , Tiadiazóis/química
7.
Mol Pain ; 17: 17448069211058004, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34894846

RESUMO

Oxaliplatin, a platinum-based chemotherapeutic agent, frequently causes severe neuropathic pain typically encompassing cold allodynia and long-lasting mechanical allodynia. Endothelin has been shown to modulate nociceptive transmission in a variety of pain disorders. However, the action of endothelin varies greatly depending on many variables, including pain causes, receptor types (endothelin type A (ETA) and B (ETB) receptors) and organs (periphery and spinal cord). Therefore, in this study, we investigated the role of endothelin in a Sprague-Dawley rat model of oxaliplatin-induced neuropathic pain. Intraperitoneal administration of bosentan, a dual ETA/ETB receptor antagonist, effectively blocked the development or prevented the onset of both cold allodynia and mechanical allodynia. The preventive effects were exclusively mediated by ETA receptor antagonism. Intrathecal administration of an ETA receptor antagonist prevented development of long-lasting mechanical allodynia but not cold allodynia. In marked contrast, an intraplantar ETA receptor antagonist had a suppressive effect on cold allodynia but only had a partial and transient effect on mechanical allodynia. In conclusion, ETA receptor antagonism effectively prevented long-lasting mechanical allodynia through spinal and peripheral actions, while cold allodynia was prevented through peripheral actions.


Assuntos
Hiperalgesia , Neuralgia , Receptor de Endotelina A , Animais , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Oxaliplatina , Ratos , Ratos Sprague-Dawley , Receptor de Endotelina A/metabolismo
8.
Zhonghua Yi Xue Za Zhi ; 101(43): 3581-3587, 2021 Nov 23.
Artigo em Chinês | MEDLINE | ID: mdl-34808752

RESUMO

Objective: To investigate the molecular mechanism of oxaliplatin-induced chemotherapy-induced peripheral neuropathic pain (CIPNP). Methods: A total of 16 male Sprague-Dawley rats of specific pathogen-free grade were randomly divided into two groups: oxaliplatin experimental group (2.4 mg/kg oxaliplatin dissolved in 5.0% glucose solution, n=8) and control group (equal volume 5% glucose solution, n=8). The rat model of CIPNP was established by continuous administration with oxaliplatin. In addition, mechanical allodynia, thermal hyperalgesia and cold hyperalgesia were measured and compared between the two groups. To explore the molecular mechanism of oxaliplatin-induced CIPNP, the gene expression of dorsal root ganglia (DRG) from the rat model of CIPNP was analyzed using RNA sequencing (RNA-Seq). Results: Mechanical and thermal hypersensitivity was exhibited on day 7 and a stronger hypersensitivity was observed on day 14. A total of 20 152 genes were quantified by RNA-Seq, and 379 differentially expressed genes (DEGs) were obtained with absolute fold change cut-offs ≥ 2 and P value<0.05. There were 7 genes (Npy, Car3, Cdkn1a, Nts, Prc1, Ms4a7 and Ecel1) that were involved in peripheral nerve injury-related neuropathic pain. Gene ontology (GO) functional enrichment analyses indicated that the DEGs induced by oxaliplatin were involved in oxygen transport, cell division, intermediate, centromere, oxygen transporter activity, oxygen binding. Moreover, the result of Kyoto Encyclopedia of genes and genomes (KEGG) analyses highlighted that the DEGs induced by oxaliplatin were involved in malaria, African trypanosomiasis, primary immunodeficiency, peroxisome proliferator activated receptor (PPAR) signaling pathway. Conclusion: Oxaliplatin induces CIPNP via pain-related genes and signaling pathways.


Assuntos
Neuralgia , Animais , Gânglios Espinais , Hiperalgesia/induzido quimicamente , Masculino , Neuralgia/induzido quimicamente , Oxaliplatina , Ratos , Ratos Sprague-Dawley
9.
Trials ; 22(1): 753, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717717

RESUMO

BACKGROUND: Survival benefit of adjuvant radiotherapy for locally advanced gastric cancer following gastrectomy plus D2 lymphadenectomy has always been controversial. Esophagogastric junction (EGJ) adenocarcinoma, which is usually classified as gastric cancer in East Asia, often has a higher locoregional recurrence rate after operation because of its special anatomical characteristics. The aim of this study is to determine whether adjuvant radiotherapy can improve survival of locally advanced EGJ adenocarcinoma after D2 radical resection. METHODS: In this phase III, randomized, open label, controlled trial, we plan to recruit 378 patients with Siewert type II and III adenocarcinoma of EGJ, who had undergone transabdominal radical surgery and D2 lymphadenectomy, and were divided into pathological stage IIB to IIIC. All patients will be randomized 1:1 to receive either adjuvant chemotherapy alone (control group) or adjuvant chemotherapy plus chemoradiotherapy (experimental group). Patients allocated to control group will receive eight cycles of S-1 plus oxaliplatin (SOX), while the experimental group will receive two cycles of SOX followed by 45-Gy RT combined with S-1 and four additional cycles of SOX. The primary endpoint is 3-year disease-free survival rate (DFS). The secondary endpoints are 3-year overall survival rate (OS), 3-year locoregional recurrence-free survival rate (LRFS), 3-year distant metastasis-free survival rate (DMFS), and quality of life (QoL). DISCUSSION: In the past, the adjuvant treatment of EGJ adenocarcinoma needs to draw on the experience of esophageal adenocarcinoma or gastric adenocarcinoma. In this study, EGJ adenocarcinoma is considered as an independent disease, and the conclusion will provide evidence for optimal adjuvant therapy of locally advanced EGJ adenocarcinoma after D2 radical resection. TRIAL REGISTRATION: ClinicalTrials.gov NCT03973008 . Registered on 1 June 2019 (retrospectively registered), URL: https://clinicaltrials.gov/ct2/show/NCT03973008?term=NCT03973008&draw=2&rank=1.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante , Ensaios Clínicos Fase III como Assunto , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Oxaliplatina/efeitos adversos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
10.
Medicine (Baltimore) ; 100(40): e27348, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622834

RESUMO

RATIONALE: Colorectal mixed neuroendocrine-nonneuroendocrine neoplasms constitute a rare group of gastrointestinal tumors composed by both neuroendocrine and nonneuroendocrine components. Nondiagnostic macroscopic features, specific histological features, and poor awareness of the disease are responsible for the underestimated incidence and conflicting data available. Due to lack of randomized clinical trials and validated clinical guidelines, diagnostic and therapeutic approach are based on the standard of care for pure colorectal neuroendocrine carcinomas or adenocarcinomas. PATIENT CONCERNS: A 76-year-old caucasian male, without relevant medical or familial history, presented a positive faecal occult blood test during colorectal cancer screening. DIAGNOSIS: Total colonoscopy identified a rectal lesion with biopsy showing a moderate rectal adenocarcinoma staged as cT2N0M0. INTERVENTIONS: Anterior resection of the rectum with right ileostomy followed by local radiotherapy with radio-sensitising chemotherapy and adjuvant chemotherapy with capecitabine 1000 mg bid plus oxaliplatin 130 mg/m2. Due to chronic nodular pulmonary aspergillosis and chemotherapy induced immunosuppression patient was on 400 mg/daily of oral voriconazole. OUTCOMES: Overall survival of 15 months after progression under first line treatment and under palliative chemotherapy with platinum plus etoposide regimen. LESSONS: The reported case illustrates the challenge associated to the management of mixed neuroendocrine-nonneuroendocrine carcinomas due to lack of validated guidelines and scientific evidence. From diagnosis and staging to treatment, all steps must be tailored to individual clinical and histological features.


Assuntos
Adenocarcinoma/patologia , Tumor Misto Maligno/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Retais/patologia , Adenocarcinoma/terapia , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina/administração & dosagem , Evolução Fatal , Humanos , Masculino , Tumor Misto Maligno/terapia , Tumores Neuroendócrinos/terapia , Oxaliplatina/administração & dosagem , Radioterapia , Neoplasias Retais/terapia , Reto/cirurgia
11.
Int J Clin Oncol ; 26(12): 2194-2204, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34625844

RESUMO

This study aimed to investigate risk factors associated with oxaliplatin hypersensitivity reactions in cancer patients through a meta-analysis. A comprehensive retrieve of Chinese databases China National Knowledge Infrastructure, Wanfang Data, VIP Database and English databases PubMed, ScienceDirect, Embase and Cochrane library was conducted. The studies that meet the requirements for meta-analysis according to inclusion and exclusion criteria were screened and assessed for eligibility. Odds ratio (OR) / Weighted mean difference (WMD) and 95% confidence intervals (95% CIs) or calculable dichotomous and continuous raw data were extracted to perform meta-analysis using random effect model or fixed effect model on the basis of heterogeneity between studies through Review Manager 5.4 software. A total of 14 cross-sectional studies and 3367 cancer patients were included. Meta-analysis results showed that platinum exposure history (OR value 3.13, 95% CI 2.19-4.48, heterogeneity P = 0.26), allergy history (OR value 1.76, 95% CI 1.09-2.85, heterogeneity P = 0.61), platinum free interval (OR value 3.75, 95% CI 2.00-7.06, heterogeneity P = 0.83), dexamethasone premedication dose (OR value 0.28, 95% CI 0.13-0.58, heterogeneity P = 0.21) were significantly correlated to oxaliplatin hypersensitivity reactions. Gender, age, metastasis, combination with bevacizumab, XELOX regimen and cancer types were detected to have no statistically significant effect on oxaliplatin hypersensitivity reactions. Platinum exposure history, allergy history and long platinum-free interval are risk factors of oxaliplatin hypersensitivity reactions. High dexamethasone premedication dose is a protective factor of oxaliplatin hypersensitivity reactions.


Assuntos
Neoplasias Colorretais , Hipersensibilidade , Neoplasias Colorretais/tratamento farmacológico , Estudos Transversais , Humanos , Oxaliplatina/efeitos adversos , Fatores de Risco
12.
J Manag Care Spec Pharm ; 27(10): 1367-1375, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34595948

RESUMO

BACKGROUND: Pancreatic cancer is associated with low median overall survival. Combination chemotherapy regimens FOLFIRINOX and gemcitabine with nab-paclitaxel (GemNab) are the new adjuvant treatment standards for resectable pancreatic cancer. PRODIGE-24 and APACT trials demonstrated superior clinical outcomes with FOLFIRINOX and GemNab, each vs gemcitabine monotherapy. OBJECTIVE: To evaluate the cost-effectiveness of FOLFIRINOX vs GemNab for resectable pancreatic cancer in adults from the U.S. payer perspective, in order to inform decision makers about which of these treatments is optimal. METHODS: A Markov model with 3 disease states (relapse free, progressive disease, and death) was developed. Cycle length was 1 month, and time horizon was 10 years. Transition probabilities were derived from PRODIGE-24 and APACT survival data. All cost and utility input parameters were obtained from published literature. Cost-effectiveness analysis was performed to obtain total costs, quality-adjusted life-years (QALYs), life-years (LYs), and incremental cost-effectiveness ratio (ICER). A 3% annual discount rate was applied to costs and outcomes. The effect of uncertainty on model parameters was assessed with 1-way and probabilistic sensitivity analysis (PSA). RESULTS: Our analysis estimated that the cost for FOLFIRINOX was $40,831 higher than GemNab ($99,669 vs. $58,837). Despite increased toxicity, FOLFIRINOX was associated with additional 0.18 QALYs and 0.25 LYs compared with GemNab (QALY: 1.65 vs. 1.47; LY: 2.09 vs. 1.84). The ICER for FOLFIRINOX vs GemNab was $226,841 per QALY and $163,325 per LY. FOLFIRINOX was not cost-effective at a willingness-to-pay (WTP) threshold of $200,000 per QALY, and this was confirmed by the PSA. CONCLUSIONS: Total monthly cost for FOLFIRINOX was approximately 1.7 times higher than GemNab. If the WTP threshold increases to or above $250,000 per QALY, FOLFIRINOX then becomes a cost-effective treatment option. DISCLOSURES: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare.


Assuntos
Albuminas/economia , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Desoxicitidina/análogos & derivados , Paclitaxel/economia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Análise Custo-Benefício/métodos , Desoxicitidina/economia , Intervalo Livre de Doença , Quimioterapia Combinada/economia , Feminino , Fluoruracila/economia , Humanos , Irinotecano/economia , Leucovorina/economia , Masculino , Cadeias de Markov , Oxaliplatina/economia , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos
13.
BMC Cancer ; 21(1): 1086, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625033

RESUMO

BACKGROUND: Perioperative FLOT (5-fluorouracil, oxaliplatin and docetaxel) has recently become the gold standard treatment for fit patients with operable gastric (GC) or gastroesophageal (GEJ) adenocarcinoma, getting a 5-year overall survival (OS) of 45%, over 23% with surgery alone. METHODS: RealFLOT is an Italian, multicentric, observational trial, collecting data from patients with resectable GC or GEJ adenocarcinoma treated with perioperative FLOT. Aim of the study was to describe feasibility and safety of FLOT, pathological complete response rate (pCR), surgical outcomes and overall response rate (ORR) in an unselected real-world population. Additional analyses evaluated the correlation between pCR and survival and the prognostic role of microsatellite instability (MSI) status. RESULTS: Of 206 patients enrolled that received perioperative FLOT at 15 Italian centers, 124 (60.2%) received at least 4 full-dose cycles, 190 (92.2%) underwent surgery, and 142 (68.9%) started the postoperative phase. Among patients who started the postoperative phase, 105 (51.0%) received FLOT, while 37 (18%) received de-intensified regimens, depending on clinical condition or previous toxicities. pCR was achieved in 7.3% of cases. Safety profile was consistent with literature. Neutropenia was the most common G 3-4 adverse event (AE): 19.9% in the preoperative phase and 16.9% in the postoperative phase. No toxic death was observed and 30-day postoperative mortality rate was 1.0%. ORR was 45.6% and disease control rate (DCR) was 94.2%. Disease-free survival (DFS) and OS were significantly longer in case of pCR (p = 0.009 and p = 0.023, respectively). A trend towards better DFS was observed among MSI-H patients. CONCLUSIONS: These real-world data confirm the feasibility of FLOT in an unselected population, representative of the clinical practice. pCR rate was lower than expected, nevertheless we confirm pCR as a predictive parameter of survival. In addition, MSI-H status seems to be a positive prognostic marker also in patients treated with taxane-containing triplets.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Junção Esofagogástrica , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Itália , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia
14.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(3): 240-247, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-34645168

RESUMO

Objective: To investigate the safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with different types of peritoneal metastasis. Methods: A prospective study "one arm exploratory clinical study of conversion therapy of apatinib with S-1 and oxaliplatin in the treatment of advanced gastric cancer" (clinical registration ChiCTR-ONC-17010430) from medical record database was retrospectively analyzed. Patients aged 18-70 years with gastric cancer peritoneal metastasis confirmed by histology and laparoscopic exploration, and had not receive radiotherapy, chemotherapy, targeted therapy or immunotherapy before were enrolled. Before operation, the patients received 6 cycles of S-1 (80-120 mg/d, d1-d14) and oxaliplatin (130 mg/m(2), d1), and 5 cycles of apatinib (500 mg/d, d1-d21) conversion regimen. Three weeks after chemotherapy, whether the operation was performed or not depending on re-evaluation and patient preference. The main outcome were adverse reactions, and the secondary outcome were objective remission rate (ORR), disease control rate (DCR), and overall survival (OS) rate. The follow-up period was up to May 2020. Results: A total of 27 patients with gastric cancer peritoneal metastasis were enrolled in this study. There were 13 males and 14 females, with a median age of 58 (30-68) years old. There were 9 cases of P1a, 5 cases of P1b, and 13 cases of P1c. There were 14 cases with 1-5 scores of PCI (peritoneal cancer index), and 13 cases with 6 scores or above. The incidence of adverse reactions was 100%. The most common adverse reactions were hematological events including leucopenia (70.4%, 19/27) and granulocytopenia (74.1%, 20/27). Non-hematological adverse events included fatigue (51.9%, 14/27) and oral mucositis (37.0%, 10/27). One patient was withdrawn due to grade 4 thrombocytopenia. Among 26 patients with feasible efficacy evaluation, 18 (69.2%) achieved partial remission, 3 (11.5%) achieved stable disease, and 5 (19.2%) disease progression. The objective remission rate was 69.2% (18/26) and the disease control rate was 80.8% (21/26). Fourteen patients underwent surgery, including 6 patients undergoing R0 resection with the R0 resection rate of 42.9% (6/14). The postoperative pathological response rate was 64.3% (9/14). The follow-up time was 12-40 months, and the follow-up rate was 100%. The 1-year OS rate was 65.2% and the survival time was (14.0±1.7) months. The 1-year OS rates of P1a/P1b group and P1c group were 81.8% and 42.0% respectively, whose difference was statistically significant (P=0.041). The 1-year OS rates of PCI 1-5 group and PCI ≥6 group were 67.3% and 38.5% respectively, whose difference was statistically significant (P=0.022). Conclusion: In the conversion treatment of gastric cancer peritoneal metastasis, the safety of apatinib combined with oxaliplatin and S-1 is acceptable, and this regimen shows a good short-term survival efficacy in patients with P1a/P1b and PCI of 1-5.


Assuntos
Intervenção Coronária Percutânea , Neoplasias Peritoneais , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina , Neoplasias Peritoneais/tratamento farmacológico , Estudos Prospectivos , Piridinas , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico
15.
Molecules ; 26(19)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34641590

RESUMO

In the few last years, nanosystems have emerged as a potential therapeutic approach to improve the efficacy and selectivity of many drugs. Cyclodextrins (CyDs) and their nanoparticles have been widely investigated as drug delivery systems. The covalent functionalization of CyD polymer nanoparticles with targeting molecules can improve the therapeutic potential of this family of nanosystems. In this study, we investigated cross-linked γ- and ß-cyclodextrin polymers as carriers for doxorubicin (ox) and oxaliplatin (Oxa). We also functionalized γ-CyD polymer bearing COOH functionalities with arginine-glycine-aspartic or arginine moieties for targeting the integrin receptors of cancer cells. We tested the Dox and Oxa anti-proliferative activity in the presence of the precursor polymer with COOH functionalities and its derivatives in A549 (lung, carcinoma) and HepG2 (liver, carcinoma) cell lines. We found that CyD polymers can significantly improve the antiproliferative activity of Dox in HepG2 cell lines only, whereas the cytotoxic activity of Oxa resulted as enhanced in both cell lines. The peptide or amino acid functionalized CyD polymers, loaded with Dox, did not show any additional effect compared to the precursor polymer. Finally, studies of Dox uptake showed that the higher antiproliferative activity of complexes correlates with the higher accumulation of Dox inside the cells. The results show that CyD polymers could be used as carriers for repositioning classical anticancer drugs such as Dox or Oxa to increase their antitumor activity.


Assuntos
Antineoplásicos/uso terapêutico , Celulose/uso terapêutico , Ciclodextrinas/uso terapêutico , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/uso terapêutico , Oxaliplatina/uso terapêutico , Células A549 , Motivos de Aminoácidos , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Celulose/química , Ciclodextrinas/química , Doxorrubicina/química , Portadores de Fármacos/química , Células Hep G2 , Humanos , Nanopartículas/química , Oxaliplatina/química , beta-Ciclodextrinas/química , beta-Ciclodextrinas/uso terapêutico , gama-Ciclodextrinas/química , gama-Ciclodextrinas/uso terapêutico
16.
Gan To Kagaku Ryoho ; 48(9): 1173-1175, 2021 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-34521799

RESUMO

A 70-year-old man, who had undergone distal gastrectomy for early gastric cancer at 63-year-old, had multiple liver metastases from remnant gastric cancer, which was diagnosed as cT3(SS), N0, M1, cStage Ⅳ. After a regimen consisting of 8 courses of capecitabine plus oxaliplatin and 2 courses of S-1 was administered, clinical CR was confirmed for the remnant gastric cancer and multiple liver metastases. Chemotherapy was administered for 10 months and discontinued for side effects and the needs of the patient. Anticoagulant drugs were administered for the onset of cerebral infarction after he vomited blood. A gastric ulcer in the oral side of the anastomotic portion was detected and diagnosed as poorly differentiated adenocarcinoma. Multiple liver metastases could not be detected by PET-CT, and we performed a total gastrectomy of the remnant stomach. The patient remains relapse-free 4 years and 10 months after chemotherapy(3 years and 10 months after discontinuing chemotherapy).


Assuntos
Neoplasias Hepáticas , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Gastrectomia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Recidiva Local de Neoplasia , Oxaliplatina/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
17.
Exp Cell Res ; 407(2): 112827, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34508743

RESUMO

As the new platinum drug oxaliplatin has been widely used in clinical treatment of colorectal cancer (CRC), oxaliplatin resistance has become a burning problem. In this study, higher expression of PARP-1 binding protein (PARPBP) was detected in oxaliplatin-resistant CRC (OR-CRC) cells than in non-resistant cells. Further research showed that kinesin family member 18 b (KIF18b) induced the overexpression of PARPBP, sustaining oxaliplatin resistance in OR-CRC cells. Through exploring the PARPBP gene promoter, we found that SP1-recruited DNMT3b methylated PARPBP promoter to suppress transcription in CRC cells, and increased KIF18b attenuated the recruitment of DNMT3b to PARPBP promoter by directly interacting with SP1 in OR-CRC cells. Clinical analysis suggested a positive relationship between KIF18b and PARPBP in CRC tissues and indicated poor prognosis in CRC patients with high level of KIF18b or PARPBP. In summary, KIF18b-induced PARPBP contributes to the resistant phenotype of OR-CRC.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Metilação de DNA , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Oxaliplatina/farmacologia , Idoso , Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Prognóstico , Regiões Promotoras Genéticas , Taxa de Sobrevida , Células Tumorais Cultivadas
19.
Int J Clin Pract ; 75(11): e14863, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34516723

RESUMO

AIM: Oxaliplatin-based adjuvant chemotherapy was demonstrated to be beneficial for stage III or high-risk stage II colorectal cancer (CRC). Moreover, a recent international collaborative trial suggested 3-months CAPOX as an alternative regimen for low-risk stage III colorectal cancer (CRC) patients. Thus, it is important to clarify the frequency and predictive markers of dose-limiting toxicities (DLTs) developed within the short-course CAPOX cycles. METHODS: We investigated CRC patients who underwent radical surgery and adjuvant CAPOX therapy at our hospital between December 2010 and February 2021. Patients who received initially reduced doses of CAPOX and those who had early recurrence were excluded. We reviewed the age, sex, comorbidities, physical, laboratory and oncological data and other perioperative factors. The associations between these variables and early DLTs within four cycles of CAPOX were examined by multivariate analyses using logistic regression models. RESULTS: Among 168 patients (96 men, mean age: 58.3 years), 120 (71%) developed early DLTs. Patients with early DLTs were predominantly women and sarcopenic and habitual alcohol consumers. On multivariate analyses, only the female sex was an independent predictive factor for early DLTs (odds ratio: 2.61, P = .027). CONCLUSION: Women were prone to early DLTs during adjuvant CAPOX in the current study. Doctors should be aware of the sex difference in the incidence of early DLTs, adjust the CAPOX dosage and provide supportive care for female CRC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Capecitabina/uso terapêutico , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico
20.
ESMO Open ; 6(5): 100270, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34547581

RESUMO

BACKGROUND: In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment. PATIENTS AND METHODS: In 14-day cycles, patients received FTD/TPI 35 mg/m2 (twice daily, days 1-5) plus oxaliplatin 85 mg/m2 (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B). Patients in Cohort B had confirmed MSS status. RESULTS: In total, 54 patients were enrolled: 37 in cohort A and 17 in cohort B. Recruitment in cohort B was stopped early due to the low response rate (RR) observed at interim analyses of efficacy. The most common adverse events (AEs) in cohort A were neutropenia/decreased neutrophils (75.7%), nausea (59.5%), vomiting (40.5%), diarrhoea (37.8%), peripheral sensory neuropathy (37.8%), fatigue (35.1%) and decreased appetite (35.1%). In cohort B, the most common AEs were neutropenia/decreased neutrophils (70.6%), diarrhoea (58.8%), nausea (47.1%), vomiting (47.1%), fatigue (47.1%), asthenia (41.2%), paraesthesia (41.2%), thrombocytopenia/decreased platelets (35.3%) and decreased appetite (35.3%). Confirmed objective RR was 17.1% in cohort A and 7.1% in cohort B; the corresponding values for median progression-free survival in the two cohorts were 6.3 and 6.0 months. CONCLUSION: FTD/TPI plus oxaliplatin and bevacizumab or nivolumab had an acceptable safety profile and demonstrated antitumour activity in previously treated patients with mCRC.


Assuntos
Neoplasias Colorretais , Trifluridina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Humanos , Nivolumabe/uso terapêutico , Oxaliplatina/uso terapêutico , Pirrolidinas , Timina , Trifluridina/uso terapêutico
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