RESUMEN
Melanoma either intrinsically possesses resistance or rapidly acquires resistance to anti-tumor therapy, which often leads to local recurrence or distant metastasis after resection. In this study, we found histone 3 lysine 27 (H3K27) demethylated by an inhibitor of histone methyltransferase EZH2 could epigenetically reverse the resistance to chemo-drug paclitaxel (PTX), or enhance the efficacy of immune checkpoint inhibitor anti-TIGIT via downregulating TIGIT ligand CD155. Next, to address the complexity in the combination of multiple bioactive molecules with distinct therapeutic properties, we developed a polysaccharides-based organohydrogel (OHG) configured with a heterogenous network. Therein, hydroxypropyl chitosan (HPC)-stabilized emulsions for hydrophobic drug entrapment were crosslinked with oxidized dextran (Odex) to form a hydrophilic gel matrix to facilitate antibody accommodation, which demonstrated a tunable sustained release profile by optimizing emulsion/gel volume ratios. As results, local injection of OHG loaded with EZH2 inhibitor UNC1999, PTX and anti-TIGIT did not only synergistically enhance the cytotoxicity of PTX, but also reprogrammed the immune resistance via bi-directionally blocking TIGIT/CD155 axis, leading to the recruitment of cytotoxic effector cells into tumor and conferring a systemic immune memory to prevent lung metastasis. Hence, this polysaccharides-based OHG represents a potential in-situ epigenetic-, chemo- and immunotherapy platform to treat unresectable metastatic melanoma.
Asunto(s)
Quitosano , Dextranos , Proteína Potenciadora del Homólogo Zeste 2 , Epigénesis Genética , Melanoma , Proteína Potenciadora del Homólogo Zeste 2/antagonistas & inhibidores , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/inmunología , Quitosano/química , Quitosano/análogos & derivados , Dextranos/química , Animales , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanoma/inmunología , Ratones , Humanos , Epigénesis Genética/efectos de los fármacos , Paclitaxel/farmacología , Paclitaxel/química , Paclitaxel/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Hidrogeles/química , Línea Celular Tumoral , Receptores Inmunológicos/antagonistas & inhibidores , Receptores Inmunológicos/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/químicaRESUMEN
Treatment options for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) remain scarce. This study aims to evaluate the efficacy and safety of combining anlotinib and sintilimab plus chemotherapy as a second line or later therapy for ES-SCLC patients. This is a phase II clinical trial (ChiCTR2100049390) conducting at Shandong Cancer Hospital. Patients with ES-SCLC and received at least one prior systemic treatment were enrolled. The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. The primary endpoint was objective response rate (ORR). Circulating tumor DNA sequencing was employed for exploratory analysis. From July 2021 to April 2023, 25 eligible patients were enrolled. The confirmed ORR was 60% (95% CI: 38.7-78.9%) and the DCR was 76% (95% CI: 54.9-90.6%). The mPFS was 6.0 months (95% CI: 5.4-9.7), and the 6-month PFS rate was 49.2%. The mOS was 13.4 months (95% CI: 11.8-NR), with a 12-month survival rate of 62.2%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with the most common being fatigue (40%) and nausea (32%). TRAEs of Grade 3 or higher were reported in 12% of patients. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Indoles , Neoplasias Pulmonares , Quinolinas , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Anciano , Indoles/administración & dosificación , Indoles/uso terapéutico , Indoles/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Estadificación de Neoplasias , AlbúminasRESUMEN
OBJECTIVE: Aim: To analyze the results of treatment of patients with oropharyngeal carcinoma. PATIENTS AND METHODS: Materials and Methods: 276 patients with oropharyngeal carcinoma were treated in 2008-2021. Neoadjuvant chemotherapy consisted of three to six cycles: paclitaxel 175 mg/m2 and carboplatin 350 mg/m2 (or cisplatin 100 mg/m2) on the first day. The interval between cycles was 21 days. After the cycles, all patients were prescribed a course of radiation therapy in a total focal dose (TFD) of 65 Gy. The outcome of treatment was assessed by the degree of tumor regression according to RECIST criteria one month after the end of combination treatment. Statistical processing was performed using STATISTICA 6.1 software (StatSoftInc). RESULTS: Results: The three- and five-year survival rates of the examined patients with oropharyngeal carcinoma after treatment were 40.8% respectively (95% CI 33.7 - 47.9) and 27.0%, (95% CI 20.6 - 33, 4) with a median survival of 36 months with 95% CI (35.5 - 40.2). Processing was performed using STATISTICA 6.1 software (StatSoftInc). CONCLUSION: Сonclusions: Analysis of treatment of patients with oropharyngeal carcinoma with predominance of squamous cell carcinoma (90.6%), localized primarily in the palatine tonsil (73.2%), with the most common stages T3N1M0 (30.1%) and T3N1M0 %), with regional metastases to the lymph nodes of the neck (89.9%), showed that the effectiveness of treatment of patients is quite high, because in most of the examined in the short term after combined treatment there was complete or partial regression of the tumor (91.7%), no progression of the oncological process was detected in any of them.
Asunto(s)
Neoplasias Orofaríngeas , Paclitaxel , Humanos , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/tratamiento farmacológico , Neoplasias Orofaríngeas/patología , Masculino , Femenino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Anciano , Resultado del Tratamiento , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Carboplatino/administración & dosificación , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tasa de Supervivencia , Terapia NeoadyuvanteRESUMEN
BACKGROUND: Programmed cell death-1 (PD-1) blockade improves survival in patients with advanced esophageal squamous cell carcinoma (ESCC). However, the efficacy of taxanes after exposure to PD-1 blockade remains unclear in patients with advanced ESCC. METHODS: We retrospectively analyzed the clinical outcomes of advanced ESCC patients treated with taxanes (paclitaxel or docetaxel) with/without prior exposure to PD-1 blockade (Exposed /Naïve group) at National Cancer Center Hospital from June 2016 to December 2020. RESULTS: Ninety-nine patients (Exposed group, n = 32; Naïve group, n = 67) were included. The objective response rate (ORR) of the Exposed group was significantly higher than that of the Naïve group (37.5% vs. 13.4%, p = 0.009). The median progression-free survival was similar between the Exposed and Naïve groups (3.8 vs. 2.8 months, HR 1.12, 95% CI 0.65-1.86, p = 0.66). PD-1 blockade exposure independently predicated higher ORR to taxanes in multivariate analysis. Grade ≥ 3 adverse events were comparable between the Exposed and Naïve groups (45.8% vs. 40.3%, p = 0.64). CONCLUSIONS: Taxanes following PD-1 blockade in advanced ESCC showed a higher ORR but similar PFS compared to taxanes without prior PD-1 exposure.
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Docetaxel , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Paclitaxel , Humanos , Masculino , Femenino , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Persona de Mediana Edad , Anciano , Docetaxel/uso terapéutico , Docetaxel/efectos adversos , Docetaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Paclitaxel/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Taxoides/efectos adversos , Taxoides/uso terapéutico , Supervivencia sin Progresión , Resultado del Tratamiento , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
BACKGROUND: Despite the recognized therapeutic potential of programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in advanced esophageal squamous cell carcinoma (ESCC), their role in neoadjuvant therapy and reliable efficacy biomarkers remain elusive. MATERIALS AND METHODS: We retrospectively analyzed locally advanced ESCC patients who underwent surgery following a 2-cycle platinum and paclitaxel-based treatment, with or without PD-1 inhibitors (January 2020-March 2023). We assessed peripheral blood indexes and tertiary lymphoid structures (TLS) density to evaluate their impact on pathological response and prognosis, leading to a clinical prediction model for treatment efficacy and survival. RESULTS: Of the 157 patients recruited, 106 received immunochemotherapy (ICT) and 51 received chemotherapy (CT) alone. The ICT group demonstrated a superior pathological response rate (PRR) (47.2% vs. 29.4%, p = 0.034) with comparable adverse events and postoperative complications. The ICT group also showed a median disease-free survival (DFS) of 39.8 months, unattained by the CT group. The 1-year DFS and overall survival (OS) rates were 73% and 91% for the ICT group, and 68% and 81% for the CT group, respectively. We found higher baseline activated T cells, lower baseline Treg cells, and a decreased posttreatment total lymphocyte and CD4+/CD8+ ratio predicted an enhanced PRR. Reduced posttreatment CD4+/CD8+ ratio and increased NK cells were associated with prolonged survival, while higher TLS density indicated poorer prognosis. Among ICT group, a lower posttreatment CD4+/CD8+ ratio indicated longer DFS and reduced posttreatment B cells indicated longer OS. A nomogram integrating these predictors was developed to forecast treatment efficacy and survival. CONCLUSION: The combination of PD-1 inhibitors and chemotherapy appears promising for locally advanced ESCC. Evaluating the differentiation status and dynamic changes of peripheral blood immune cells may provide valuable predictive insights into treatment efficacy and prognosis.
Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Terapia Neoadyuvante , Humanos , Masculino , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Femenino , Terapia Neoadyuvante/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/tratamiento farmacológico , Anciano , Inmunoterapia/métodos , Subgrupos Linfocitarios/inmunología , Pronóstico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Adulto , EsofagectomíaRESUMEN
BACKGROUND: Neoadjuvant chemotherapy (NAC) is an effective treatment for locally advanced breast cancer (BC). However, there are no effective biomarkers for evaluating its efficacy. CDR1-AS, well known for its important role in tumorigenesis, is a famous circular RNA involved in the chemosensitivity of cancers other than BC. However, the predictive role of CDR1-AS in the efficacy and prognosis of NAC for BC has not been fully elucidated. We herein aimed to clarify this role. METHODS: The present study included patients treated with paclitaxel-cisplatin-based NAC. The expression of CDR1-AS was detected by real-time quantitative reverse transcription polymerase chain reaction testing. The predictive value of CDR1-AS expression was examined in pathological complete response (pCR) after NAC using logistic regression analysis. The relationship between CDR1-AS expression and survival was demonstrated using the Kaplan-Meier method, and tested by log-rank test and Cox proportional hazards regression model. RESULTS: The present study enrolled 106 patients with BC. Multivariate logistic regression analysis revealed that CDR1-AS expression was an independent predictive factor for pCR (odds ratio [OR] = 0.244; 95% confidence interval [CI] 0.081-0.732; p = 0.012). Furthermore, pCR benefits with low CDR1-AS expression were observed across all subgroups. The Kaplan-Meier curves and log-rank test suggested that the CDR1-AS high-expression group showed significantly better disease-free survival (DFS; log-rank p = 0.022) and relapse-free survival (RFS; log-rank p = 0.012) than the CDR1-AS low-expression group. Multivariate analysis revealed that CDR1-AS expression was an independent prognostic factor for DFS (adjusted HR = 0.177; 95% CI 0.034-0.928, p = 0.041), RFS (adjusted HR = 0.061; 95% CI 0.006-0.643, p = 0.020), and distant disease-free survival (adjusted HR = 0.061; 95% CI 0.006-0.972, p = 0.047). CONCLUSIONS: CDR1-AS may be a potential novel predictive biomarker of pCR and survival benefit in patients with locally advanced BC receiving NAC. This may help identify specific chemosensitive individuals and build personalized treatment strategies.
Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Terapia Neoadyuvante , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Femenino , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Estudios Prospectivos , Adulto , ARN Circular/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , China/epidemiología , Paclitaxel/uso terapéutico , Paclitaxel/administración & dosificación , Pueblos del Este de AsiaRESUMEN
The WHO (World Health Organization) conducted an elimination of cervical cancer program using triple pillar intervention strategy to target 90%-70%-90% of women before the year 2030, including (1) a full vaccination of HPV (human papillomavirus) vaccine to 90% of girls <15 years of age; (2) a high-performance screening procedure to 70% of women during the reproductive age (at the age of 35 and 45 years of age); and (3) an appropriate and adequate treatment to 90% of women with confirmed diagnosis of cervical lesions. Among the aforementioned three pillars, a full HPV vaccination has been introduced in our previous review, of which we have discussed the policy and strategy of HPV vaccination in the world and also reviewed the efficacy of HPV vaccination, with a successful reduction of over 90% of HPV-associated neoplasms. The aims of the current review will target another pillar-an appropriate and adequate treatment to 90% of women with confirmed diagnosis of cervical lesions. Since the early-stage cervical cancer has a favorable outcome and the treatment recommendation has been established, therefore, the current review focuses on women with persistent, recurrent and metastatic cervical cancers (advanced cervical cancers), which are still a biggest challenge based on its extremely worse outcomes before the introduction of immune checkpoint inhibitors (ICIs). Integration of ICIs into conventional chemotherapy (paclitaxel-cisplatin) has become the new standard therapy for those patients with advanced cervical cancers. The recent clinical trials, such as KENOTE 826 and KENOTE A18 showing a dramatical improvement of both progression free survival and overall survival have approved the therapeutic efficacy of this combination as ICI plus paclitaxel-platinum (cisplatin or carboplatin) with/without bevacizumab to women with persistent, recurrent and metastatic cervical cancers.
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Recurrencia Local de Neoplasia , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/tratamiento farmacológico , Recurrencia Local de Neoplasia/terapia , Vacunas contra Papillomavirus/administración & dosificación , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéuticoRESUMEN
BACKGROUND: Epithelial ovarian cancer (EOC) is the deadliest gynaecological cancer with high mortality rates driven by the common development of resistance to chemotherapy. EOC frequently invades the omentum, an adipocyte-rich organ of the peritoneum and omental adipocytes have been implicated in promoting disease progression, metastasis and chemoresistance. The signalling mechanisms underpinning EOC omentum tropism have yet to be elucidated. METHODS: Three-dimensional co-culture models were used to explore adipocyte-EOC interactions. The impact of adipocytes on EOC proliferation, response to therapy and invasive capacity was assessed. Primary adipocytes and omental tissue were isolated from patients with ovarian malignancies and benign ovarian neoplasms. Exosomes were isolated from omentum tissue conditioned media and the effect of omentum-derived exosomes on EOC evaluated. Exosomal microRNA (miRNA) sequencing was used to identify miRNAs abundant in omental exosomes and EOC cells were transfected with highly abundant miRNAs miR-21, let-7b, miR-16 and miR-92a. RESULTS: We demonstrate the capacity of adipocytes to induce an invasive phenotype in EOC populations through driving epithelial-to-mesenchymal transition (EMT). Exosomes secreted by omental tissue of ovarian cancer patients, as well as patients without malignancies, induced proliferation, upregulated EMT markers and reduced response to paclitaxel therapy in EOC cell lines and HGSOC patient samples. Analysis of the omentum-derived exosomes from cancer patients revealed highly abundant miRNAs that included miR-21, let-7b, miR-16 and miR-92a that promoted cancer cell proliferation and protection from chemotherapy when transfected in ovarian cancer cells. CONCLUSIONS: These observations highlight the capacity of omental adipocytes to generate a pro-tumorigenic and chemoprotective microenvironment in ovarian cancer and other adipose-related malignancies.
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Adipocitos , Exosomas , MicroARNs , Invasividad Neoplásica , Neoplasias Ováricas , Paclitaxel , Femenino , Exosomas/metabolismo , Humanos , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Neoplasias Ováricas/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Adipocitos/metabolismo , Adipocitos/efectos de los fármacos , Adipocitos/patología , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Epiplón/patología , Epiplón/metabolismo , Proliferación Celular/efectos de los fármacos , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/patología , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/metabolismo , Transición Epitelial-Mesenquimal/genética , Transición Epitelial-Mesenquimal/efectos de los fármacosRESUMEN
BACKGROUND: The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions. METHODS: REC-CAGEFREE I was an open-label, randomised, non-inferiority trial conducted at 43 sites in China. After successful lesion pre-dilatation, patients aged 18 years or older with de novo, non-complex coronary artery disease (irrespective of target vessel diameter) and an indication for percutaneous coronary intervention were randomly assigned (1:1), via a web-based centralised system with block randomisation (block size of two, four, or six) and stratified by site, to paclitaxel-coated balloon angioplasty with the option of rescue stenting due to an unsatisfactory result (DCB group) or intended deployment of second-generation thin-strut sirolimus-eluting stents (DES group). The primary outcome was the device-oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularisation) assessed at 24 months in the intention-to-treat (ITT) population (ie, all participants randomly assigned to treatment). Non-inferiority was established if the upper limit of the one-sided 95% CI for the absolute risk difference was smaller than 2·68%. Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT04561739. It is closed to accrual and extended follow-up is ongoing. FINDINGS: Between Feb 5, 2021, and May 1, 2022, 2272 patients were randomly assigned to the DCB group (1133 [50%]) or the DES group (1139 [50%]). Median age at the time of randomisation was 62 years (IQR 54-69), 1574 (69·3%) of 2272 were male, 698 (30·7%) were female, and all patients were of Chinese ethnicity. 106 (9·4%) of 1133 patients in the DCB group received rescue DES after unsatisfactory DCB angioplasty. As of data cutoff (May 1, 2024), median follow-up was 734 days (IQR 731-739). At 24 months, the DoCE occurred in 72 (6·4%) of 1133 patients in the DCB group and 38 (3·4%) of 1139 in the DES group, with a risk difference of 3·04% in the cumulative event rate (upper boundary of the one-sided 95% CI 4·52; pnon-inferiority=0·65; two-sided 95% CI 1·27-4·81; p=0·0008); the criterion for non-inferiority was not met. During intervention, no acute vessel closures occurred in the DCB group and one (0·1%) of 1139 patients in the DES group had acute vessel closure. Periprocedural myocardial infarction occurred in ten (0·9%) of 1133 patients in the DCB group and nine (0·8%) in the DES group. INTERPRETATION: In patients with de novo, non-complex coronary artery disease, irrespective of vessel diameter, a strategy of DCB angioplasty with rescue stenting did not achieve non-inferiority compared with the intended DES implantation in terms of the DoCE at 2 years, which indicates that DES should remain the preferred treatment for this patient population. FUNDING: Xijing Hospital and Shenqi Medical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
Asunto(s)
Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Paclitaxel , Humanos , Masculino , Femenino , Persona de Mediana Edad , Angioplastia Coronaria con Balón/métodos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Enfermedad de la Arteria Coronaria/terapia , Anciano , Sirolimus/uso terapéutico , Sirolimus/administración & dosificación , Resultado del Tratamiento , Materiales Biocompatibles Revestidos , China/epidemiología , Intervención Coronaria Percutánea/métodosRESUMEN
Objective: To assess the efficacy of neoadjuvant treatment with PD-1 (programmed cell death protein 1) inhibitors combined with paclitaxel (albumin-conjugated) and cisplatin (TP regimen) for locally advanced hypopharyngeal squamous cell carcinoma and laryngeal organ function preservation. Methods: Data of 53 patients, including 51 males and 2 females, aged 38-70 years old, who were diagnosed with locally advanced hypopharyngeal squamous carcinoma confirmed by histology and enhanced CT at the Cancer Prevention and Control Center of Sun Yat-sen University during the initial treatment from January 1, 2019 to January 15, 2023, were retrospectively analyzed. All patients received neoadjuvant therapy with PD-1 inhibitors combined with albumin-bound paclitaxel (260 mg/m2) and cisplatin (60 mg/m2) for 3 to 4 cycles. The main outcome measures were larynx dysfunction-free survival (LDFS), overall survival (OS), and progression-free survival (PFS). Survival curves were plotted using the Kaplan-Meier method, and Cox multifactorial analysis was further performed if Cox univariate analysis was statistically significant. Results: The overall efficiency was 90.6% (48/53). The 1-year and 2-year LDFS rates were 83.8% (95%CI: 74.0% to 94.8%) and 50.3% (95%CI: 22.1% to 91.6%), the 1-year and 2-year OS rates were 95.2% (95%CI: 88.9% to 100.0%) and 58.2% (95%CI: 25.6% to 81.8%), and the 1-year and 2-year PFS rates were 83.9% (95%CI: 74.2% to 94.9%) and 53.5% (95%CI: 32.1% to 89.1%). Adverse events associated with the neoadjuvant therapy were mainly myelosuppression (45.3%), gastrointestinal reactions (37.7%) and hypothyroidism (20.8%). Conclusion: The neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma using PD-1 inhibitors combined with paclitaxel and cisplatin can provide with a higher survival rate with a improved laryngeal organ function preservation rate.
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Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Neoplasias Hipofaríngeas , Terapia Neoadyuvante , Paclitaxel , Humanos , Masculino , Persona de Mediana Edad , Femenino , Cisplatino/uso terapéutico , Paclitaxel/uso terapéutico , Paclitaxel/administración & dosificación , Adulto , Anciano , Neoplasias Hipofaríngeas/terapia , Neoplasias Hipofaríngeas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Albúminas/uso terapéutico , Albúminas/administración & dosificación , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidoresRESUMEN
A 73-year-old man with lung squamous cell carcinoma was administered carboplatin + nab-paclitaxel + pembrolizumab for four cycles. Subsequently, he presented with multiple purpuras on his extremities, joint swelling on his fingers, abdominal pain, and diarrhea, accompanied by acute kidney injury (AKI), increased proteinuria, hematuria, and elevated C-reactive protein levels. Skin biopsy showed leukocytoclastic vasculitis as well as IgA and C3 deposition in the vessel walls. Based on these findings, the patient was diagnosed with IgA vasculitis as an immune-related adverse event (irAE) induced by carboplatin + nab-paclitaxel + pembrolizumab. After discontinuation of pembrolizumab and glucocorticoids, the symptoms immediately resolved. Regular monitoring of skin, blood tests, and urinalysis are necessary, and the possibility of irAE IgA vasculitis should be considered in cases of purpura and AKI during treatment with immune checkpoint inhibitors.
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Albúminas , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatino , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Paclitaxel , Humanos , Masculino , Anciano , Carboplatino/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Paclitaxel/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Albúminas/efectos adversos , Albúminas/administración & dosificación , Vasculitis por IgA/inducido químicamente , Vasculitis por IgA/diagnóstico , Inmunoglobulina A , Inhibidores de Puntos de Control Inmunológico/efectos adversosRESUMEN
Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better efficacy profile without compromising efficacy.
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Resistencia a Antineoplásicos , Neoplasias Ováricas , Paclitaxel , Humanos , Femenino , Paclitaxel/uso terapéutico , Paclitaxel/administración & dosificación , Estudios Retrospectivos , Neoplasias Ováricas/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Adulto , Recurrencia Local de Neoplasia/tratamiento farmacológico , Esquema de Medicación , Antineoplásicos Fitogénicos/uso terapéutico , Anciano de 80 o más AñosRESUMEN
Purpose: To study the effects of prior pelvic radiotherapy on bone marrow suppression in recurrent cervical cancer patients during chemotherapy. Methods and materials: The cases of 129 patients with recurrent cervical cancer were reviewed, of which 77 patients had pelvic radiotherapy history and another 52 patients with no pelvic radiotherapy history were used as control group. All patients received a chemotherapy regimen of paclitaxel combined with carboplatin (TC) per 21 days for 5-6 times. Hematologic toxicity, including count of red blood cell, white blood cell and neutrophil cell and platelet, was defined by using Common Terminology Criteria for Adverse Events (version 4.0). The relationship between age, body mass index, disease free survival, pathological types, FIGO stages, radiotherapy methods and the degree of bone marrow suppression during chemotherapy was statistically analyzed, respectively, for all recurrent cervical cancer patients. Results: Among 77 patients with previous radiotherapy history, 73 recurrent patients (94.8%) had bone marrow suppression followed by chemotherapy. Recurrent cervical cancer patients without prior radiotherapy (n=52) showed a lower risk of bone marrow suppression followed by chemotherapy (n=39, 75.0%, P < 0.05). The probability of severe bone marrow suppression (grade III-IV) after chemotherapy in recurrent cervical patients with or without history of radiotherapy was 41.6% and 13.5%, respectively (P < 0.05). In univariate analysis, radiotherapy methods were associated with the incidence of grade III-IV bone marrow suppression in recurrent cervical cancer patients (P=0.005). In multivariate analysis, radiotherapy methods and extended-field radiotherapy were the risk factor of grade III-IV bone marrow suppression (χ2=16.975, P=0.001). No significant differences in the counts of white blood cell, hemoglobin and platelet were observed before chemotherapy at relapse between patients with and without prior radiotherapy. Reduction of white blood cell counts, absolute value of neutrophil cell and platelet counts composited majority type of grade III and IV bone marrow suppression. Conclusions: The prior pelvic radiotherapy significantly increased the incidence of bone marrow suppression during chemotherapy in recurrent cervical cancer patients. When treating recurrent cervical cancer patients with chemotherapy who had prior radiotherapy, especially for those experienced external beam radiation therapy, essential attention and timely intervention are recommended to ensure completion of chemotherapy and clinical efficacy.
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Médula Ósea , Recurrencia Local de Neoplasia , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Médula Ósea/efectos de la radiación , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Adulto , Anciano , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Carboplatino/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Pelvis/efectos de la radiación , Pelvis/patología , Estudios Retrospectivos , Supervivencia sin EnfermedadRESUMEN
Esophageal squamous cell carcinoma (ESCC) presents significant clinical and therapeutic challenges due to its aggressive nature and generally poor prognosis. We initiated a Phase II clinical trial (ChiCTR1900027160) to assess the efficacy of a pioneering neoadjuvant chemo-immunotherapy regimen comprising programmed death-1 (PD-1) blockade (Toripalimab), nanoparticle albumin-bound paclitaxel (nab-paclitaxel), and the oral fluoropyrimidine derivative S-1, in patients with locally advanced ESCC. This study uniquely integrates clinical outcomes with advanced spatial proteomic profiling using Imaging Mass Cytometry (IMC) to elucidate the dynamics within the tumor microenvironment (TME), focusing on the mechanistic interplay of resistance and response. Sixty patients participated, receiving the combination therapy prior to surgical resection. Our findings demonstrated a major pathological response (MPR) in 62% of patients and a pathological complete response (pCR) in 29%. The IMC analysis provided a detailed regional assessment, revealing that the spatial arrangement of immune cells, particularly CD8+ T cells and B cells within tertiary lymphoid structures (TLS), and S100A9+ inflammatory macrophages in fibrotic regions are predictive of therapeutic outcomes. Employing machine learning approaches, such as support vector machine (SVM) and random forest (RF) analysis, we identified critical spatial features linked to drug resistance and developed predictive models for drug response, achieving an area under the curve (AUC) of 97%. These insights underscore the vital role of integrating spatial proteomics into clinical trials to dissect TME dynamics thoroughly, paving the way for personalized and precise cancer treatment strategies in ESCC. This holistic approach not only enhances our understanding of the mechanistic basis behind drug resistance but also sets a robust foundation for optimizing therapeutic interventions in ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Terapia Neoadyuvante , Proteómica , Microambiente Tumoral , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/terapia , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/metabolismo , Terapia Neoadyuvante/métodos , Proteómica/métodos , Masculino , Femenino , Microambiente Tumoral/inmunología , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Paclitaxel/administración & dosificación , Inmunoterapia/métodos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Albúminas , Ácido Oxónico/administración & dosificación , Ácido Oxónico/uso terapéutico , Adulto , Combinación de Medicamentos , TegafurRESUMEN
BACKGROUND: A standardised dose-reduction strategy has not been established for the widely used gemcitabine plus nab-paclitaxel regimen in patients with metastatic pancreatic ductal adenocarcinoma. We aimed to investigate the efficacy and tolerability of alternating treatment cycles of nab-paclitaxel-gemcitabine combination therapy and gemcitabine alone versus continuous treatment with the nab-paclitaxel-gemcitabine combination. METHODS: ALPACA was a randomised, open-label, phase 2 trial conducted at 29 study centres across Germany. Patients aged 18 years or older with a histologically or cytologically confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma who had not been previously treated for advanced disease were enrolled. After an induction phase with three cycles of nab-paclitaxel-gemcitabine combination therapy (nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 administered intravenously on days 1, 8, and 15 of each 28-day cycle), patients were randomly assigned (1:1) by stratified permuted block randomisation either to continue treatment with standard nab-paclitaxel-gemcitabine or to receive alternating cycles of nab-paclitaxel-gemcitabine and gemcitabine alone. Patients and investigators were not masked to treatment allocation. Randomisation was done centrally by the study statistician using a computer-generated randomisation list, and was stratified by Karnofsky Performance Status and presence of liver metastases. The primary endpoint was the derivation of an unbiased point estimate and an associated confidence interval with a confidence coefficient of 80% for the hazard ratio (HR) for overall survival after randomisation, without testing a specific hypothesis, analysed by intention to treat in all patients who started randomised treatment. Safety was analysed according to treatment received. This trial is registered with ClinicalTrials.gov, NCT02564146, and is completed. FINDINGS: Between May 27, 2016, and May 27, 2021, 325 patients were enrolled. Following three cycles of induction treatment, 174 patients were randomly assigned: 85 to continue receiving standard nab-paclitaxel-gemcitabine, of whom 79 started treatment, and 89 to the alternating treatment schedule, of whom 88 started treatment. Of the 167 patients who started randomised treatment, 88 (53%) were female and 79 (47%) were male. Median overall survival after randomisation was 10·4 months (80% CI 9·2-12·0) in the group that received standard treatment and 10·5 months (10·2-11·1) in the group that received alternating treatment (HR 0·90, 80% CI 0·72-1·13; p=0·56). The most common adverse events of any grade were peripheral neuropathy (59 [74%] of 80 patients in the continuous treatment group vs 53 [62%] of 85 patients in the alternating treatment group) and fatigue (43 [54%] vs 44 [52%]). Treatment-emergent serious adverse events after randomisation occurred in 40 (50%) patients in the continuous treatment group and in 28 (33%) in the alternating treatment group. Fewer treatment-emergent adverse events of grade 3 or higher occurred in patients treated with alternating cycles compared with those receiving standard therapy, especially for peripheral neuropathy (17 [21%] patients in the continuous treatment group vs 12 [14%] in the alternating treatment group) and infections (16 [20%] vs nine [11%]). There were two treatment-related deaths after randomisation, both in the continuous treatment group (one multiple organ dysfunction syndrome, not treated after randomisation, and one interstitial lung disease). INTERPRETATION: Our findings suggest that a dose-reduced regimen with alternating cycles of nab-paclitaxel-gemcitabine and gemcitabine alone after three induction cycles is associated with similar overall survival to that for standard treatment with nab-paclitaxel-gemcitabine, but with improved tolerability. We therefore propose that a switch to the alternating schedule could be considered in a clinical setting for patients with metastatic pancreatic cancer who have at least stable disease after three cycles of nab-paclitaxel-gemcitabine treatment. FUNDING: Celgene/Bristol Myers Squibb.
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Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Ductal Pancreático , Desoxicitidina , Gemcitabina , Paclitaxel , Neoplasias Pancreáticas , Humanos , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Desoxicitidina/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Albúminas/administración & dosificación , Albúminas/efectos adversos , Albúminas/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/patología , Quimioterapia de Inducción/métodos , Esquema de MedicaciónRESUMEN
Prostate cancer presents as a challenging disease, as it is often characterized as an immunologically "cold" tumor, leading to suboptimal outcomes with current immunotherapeutic approaches in clinical settings. Photodynamic therapy (PDT) harnesses reactive oxygen species generated by photosensitizers (PSs) to disrupt the intracellular redox equilibrium. This process induces DNA damage in both the mitochondria and nucleus, activating the process of immunogenic cell death (ICD) and the cGAS-STING pathway. Ultimately, this cascade of events leads to the initiation of antitumor immune responses. Nevertheless, existing PSs face challenges, including suboptimal tumor targeting, aggregation-induced quenching, and insufficient oxygen levels in the tumor regions. To this end, a versatile bionic nanoplatform has been designed for the simultaneous delivery of the aggregation-induced emission PS TPAQ-Py-PF6 and paclitaxel (PTX). The cell membrane camouflage of the nanoplatform leads to its remarkable abilities in tumor targeting and cellular internalization. Upon laser irradiation, the utilization of TPAQ-Py-PF6 in conjunction with PTX showcases a notable and enhanced synergistic antitumor impact. Additionally, the nanoplatform has the capability of initiating the cGAS-STING pathway, leading to the generation of cytokines. The presence of damage-associated molecular patterns induced by ICD collaborates with these aforementioned cytokines lead to the recruitment and facilitation of dendritic cell maturation. Consequently, this elicits a systemic immune response against tumors. In summary, this promising strategy highlights the use of a multifunctional biomimetic nanoplatform, combining chemotherapy, PDT, and immunotherapy to enhance the effectiveness of antitumor treatment.
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Muerte Celular Inmunogénica , Inmunoterapia , Proteínas de la Membrana , Nucleotidiltransferasas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Neoplasias de la Próstata , Humanos , Nucleotidiltransferasas/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/patología , Muerte Celular Inmunogénica/efectos de los fármacos , Muerte Celular Inmunogénica/efectos de la radiación , Proteínas de la Membrana/metabolismo , Masculino , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Animales , Ratones , Paclitaxel/química , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Porfirinas/química , Porfirinas/farmacologíaAsunto(s)
Antineoplásicos Fitogénicos , Neoplasias Endometriales , Paclitaxel , Penfigoide Ampolloso , Humanos , Femenino , Penfigoide Ampolloso/inducido químicamente , Penfigoide Ampolloso/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Anciano , Persona de Mediana EdadRESUMEN
BACKGROUND: Long-term anti-angiogenesis leads to pruned vasculature, densely deposited extracellular matrix (ECM), and consequently reduced chemotherapy delivery in esophagogastric cancer (EGC). To address this issue, we evaluated the efficacy of adding a hyaluronidase or a NO-donor to the regimen of chemotherapy and anti-angiogenic drugs. METHODS: A patient-derived EGC xenograft model was developed. Grafted mice were randomly assigned to four experimental groups and one control group. The experimental groups received DC101, a murine angiogenesis inhibitor, and nab-paclitaxel (NPTX), with the addition of hyaluronidase (PEGPH20), or NO-donor (nitroglycerine, NTG), or their combination, respectively. We compared tumor growth during 17 days of treatment. We performed immunohistochemistry for ECM components hyaluronan (HA) and collagen, CD31 for endothelial cells, and γH2AX for DNA damage. The positively stained areas were quantified, and vessel diameters were measured using QuPath software. RESULTS: Prolonged DC101 treatment induced deposition of HA (p<0.01) and collagen (p<0.01). HA was effectively degraded by PEGPH20 (p<0.001), but not by NTG as expected. Both PEGPH20 (p<0.05) and NTG (p<0.01) dilated vessels collapsed in response to long-term DC101 treatment. However, only PEGPH20 (rather than NTG) was found to significantly inhibit tumor growth (p<0.05) in combination with NPTX and DC101. CONCLUSIONS: These findings suggest that the mechanical barrier of HA is the major reason responsible for the resistance developed during prolonged anti-angiogenesis in EGC. Incorporating PEGPH20 into the existing treatment regimen is promising to improve outcomes for patients with EGC.
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Albúminas , Inhibidores de la Angiogénesis , Neoplasias Esofágicas , Hialuronoglucosaminidasa , Neovascularización Patológica , Paclitaxel , Neoplasias Gástricas , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Paclitaxel/farmacología , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Hialuronoglucosaminidasa/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Humanos , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Albúminas/farmacología , Albúminas/administración & dosificación , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Ratones , Ácido Hialurónico/farmacología , Ratones Desnudos , Femenino , Angiogénesis , Anticuerpos MonoclonalesRESUMEN
The effect of chemotherapy for anti-glioblastoma is limited due to insufficient drug delivery across the blood-brain-barrier. Poloxamer 188-coated nanoparticles can enhance the delivery of nanoparticles across the blood-brain-barrier. This study presents the design, preparation, and evaluation of a combination of PLGA nanoparticles (PLGA NPs) loaded with methotrexate (P-MTX NPs) and PLGA nanoparticles loaded with paclitaxel (P-PTX NPs), both of which were surface-modified with poloxamer188. Cranial tumors were induced by implanting C6 cells in a rat model and MRI demonstrated that the tumors were indistinguishable in the two rats with P-MTX NPs + P-PTX NPs treated groups. Brain PET scans exhibited a decreased brain-to-background ratio which could be attributed to the diminished metabolic tumor volume. The expression of Ki-67 as a poor prognosis factor, was significantly lower in P-MTX NPs + P-PTX NPs compared to the control. Furthermore, the biodistribution of PLGA NPs was determined by carbon quantum dots loaded into PLGA NPs (P-CQD NPs), and quantitative analysis of ex-vivo imaging of the dissected organs demonstrated that 17.2 ± 0.6% of the NPs were concentrated in the brain after 48 h. The findings highlight the efficacy of combination nanochemotherapy in glioblastoma treatment, indicating the need for further preclinical studies.
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Barrera Hematoencefálica , Neoplasias Encefálicas , Glioblastoma , Metotrexato , Nanopartículas , Poloxámero , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Animales , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/metabolismo , Glioblastoma/diagnóstico por imagen , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Nanopartículas/química , Ratas , Poloxámero/química , Metotrexato/química , Metotrexato/administración & dosificación , Metotrexato/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Paclitaxel/administración & dosificación , Paclitaxel/farmacología , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/uso terapéutico , Distribución Tisular , Portadores de Fármacos/química , Masculino , Sistemas de Liberación de Medicamentos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , HumanosRESUMEN
INTRODUCTION: Primary pulmonary angiosarcoma (PPA) is a highly aggressive and rare malignancy originating from the endothelial cells of blood vessels in the lungs. PPA is an extremely rare subtype, with less than 30 cases reported to date. PPA is not only challenging to diagnose but also has a poor prognosis, often resulting in a high mortality rate within a year of diagnosis, regardless of the treatment approach. METHOD: We present the case of a 33-year-old woman with no significant past medical history who presented with abdominal pain and was incidentally found to have a right hilar mass with pleural effusion and empyema. After undergoing surgery for a perforated gastric ulcer, her pulmonary lesions were further worked up. Despite an extensive diagnostic evaluation, including imaging, bronchoscopy, and thoracotomy, establishing a diagnosis was challenging. Ultimately, PPA was diagnosed on surgical lung biopsy, and the patient was started on pazopanib and paclitaxel chemotherapy but expired after 1 month due to multiple complications. CONCLUSION: This case highlights the difficulty in diagnosing this rare tumor and its poor prognosis regardless of therapy. Greater awareness of PPA and more research are needed to improve early detection and treatment options for this deadly disease.