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Postoperative radiotherapy remains the gold standard for malignant glioma treatment. Clinical limitations, including tumor growth between surgery and radiotherapy and the emergence of radioresistance, reduce treatment effectiveness and result in local disease progression. This study aimed to develop a local drug delivery system to inhibit tumor growth before radiotherapy and enhance the subsequent anticancer effects of limited-dose radiotherapy. We developed a compound of carboplatin-loaded hydrogel (CPH) incorporated with carboplatin-loaded calcium carbonate (CPCC) to enable two-stage (peritumoral and intracellular) release of carboplatin to initially inhibit tumor growth and to synergize with limited-dose radiation (10 Gy in a single fraction) to eliminate malignant glioma (ALTS1C1 cells) in a C57BL/6 mouse subcutaneous tumor model. The doses of carboplatin in CPH and CPCC treatments were 150 µL (carboplatin concentration of 5 mg/mL) and 15 mg (carboplatin concentration of 4.1 µg/mg), respectively. Mice receiving the combination of CPH-CPCC treatment and limited-dose radiation exhibited significantly reduced tumor growth volume compared to those receiving double-dose radiation alone. Furthermore, combining CPH-CPCC treatment with limited-dose radiation resulted in significantly longer progression-free survival than combining CPH treatment with limited-dose radiation. Local CPH-CPCC delivery synergized effectively with limited-dose radiation to eliminate mouse glioma, offering a promising solution for overcoming clinical limitations.
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PURPOSE: Unresectable pediatric low-grade gliomas (LGG) usually need adjuvant therapy, and carboplatin hypersensitivity reaction (HR) commonly leads to premature treatment cessation of a standard chemotherapy regimen. In the molecular era, advances in understanding tumor genetic characteristics allowed the development of targeted therapies for this group of tumors; however, cost-effectiveness assessment of treatments, especially in low-income countries, is crucial. The aim is to describe the results of carboplatin desensitization protocol in a single center in a middle-income country. METHOD: Prospective analysis of children with LGG submitted to carboplatin desensitization from December 2017 to June 2020 with follow-up until April 2024. RESULTS: Nine patients were included. The mean age was 11 years. Five patients were male. Seven had optic pathway and two cervicomedullary location. Six had histologic diagnosis and four molecular analyses. The incidence of carboplatin reactions during the study period was 39.1%. Six patients underwent skin prick test, three with positive results. The first HR occurred, on average, around the 9th cycle of treatment. All patients had cutaneous symptoms, and five out of nine had anaphylaxis as the first reaction. 77.7% of the patients completed the protocol, and the clinical benefit rate (stable disease and partial response) was 88.8%. Six patients further required other lines of therapy. Monthly, the total cost for carboplatin was $409.09, and for target therapies (dabrafenib plus trametinib), $4929.28 to $5548.57. CONCLUSION: Our study presented an interesting and cost-effective option where desensitization allowed children with HR to be treated with first-line therapy, avoiding the discontinuation of an effective treatment.
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BACKGROUND: Many patients undergo dose reduction or early termination of chemotherapy to reduce chemoradiotherapy-related toxicity, which may increase their risk of survival. However, this strategy may result in underdosing patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). This study aimed to analyze the relationship between the relative dose intensity (RDI) and survival outcomes in patients with LA-ESCC. METHODS: This retrospective study assessed patients with LA-ESCC (cT2N + M0, cT3-4NanyM0) receiving neoadjuvant chemoradiotherapy (NCRT) with curative-intent esophagectomy. The patients received 2 courses of paclitaxel plus carboplatin (TC) combination radiotherapy prior to undergoing surgery. During NCRT, RDI was computed, defined as the received dose as a percentage of the standard dose, and the incidence of dose delays was estimated (≥ 7 days in any course cycle). The best RDI cutoff value (0.7) was obtained using ROC curve. The Kaplan-Meier survival curves were compared using the log-rank test, the treatment effect was measured using hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: We included 132 patients in this study, divided into RDI < 0.7 and RDI ≥ 0.7 groups using cut-off value of 0.7. RDI grade was an independent prognostic factor for OS. Baseline demographic and clinical characteristics were well balanced between the groups. There was no evidence that patients with RDI < 0.7 experienced less toxicity or those with RDI ≥ 0.7 resulted in more toxicity. However, patients with RDI < 0.7 who were given reduced doses had a worse overall survival [HR 0.49, 95% CI 0.27-0.88, P = 0.015]. The risk of a lower RDI increased with a longer dose delay time (P < 0.001). CONCLUSION: The RDI below 0.7 for avoiding chemoradiotherapy toxicity administration led to a reduction in the dose intensity of treatment and decreased overall survival.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Terapia Neoadyuvante , Humanos , Femenino , Masculino , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estudios Retrospectivos , Anciano , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Paclitaxel/administración & dosificación , Quimioradioterapia/métodos , Carboplatino/administración & dosificación , Esofagectomía , Adulto , Estimación de Kaplan-Meier , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
BACKGROUND: TCbHP (taxane + carboplatin + trastuzumab + pertuzumab) is the preferred neoadjuvant therapy regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, no consensus exists regarding whether specific populations may be exempt from carboplatin, allowing for de-escalation to the THP (taxane + trastuzumab + pertuzumab) regimen. Additionally, the optimal number of cycles for neoadjuvant THP remains unclear. We compared the efficacy and safety of neoadjuvant TCbHP and THP regimens, providing clinicians with a nuanced perspective to guide their treatment regimen selection. METHODS: This multicenter real-world study included patients with HER2-positive breast cancer undergoing neoadjuvant TCbHP or THP between March 2019 and February 2023. Efficacy was assessed through the pathological complete response (pCR) rate, while safety was evaluated through monitoring adverse events. RESULTS: Among 220 patients, 103 received 6 cycles of TCbHP (TCbHP×6), 83 received 6 cycles of THP (THP×6), and 34 received 4 cycles of THP (THP×4). The TCbHP×6 cohort exhibited a 66% pCR rate compared with 53% in the THP×6 cohort (P = 0.072). Subgroup analysis revealed that in patients aged ≤ 50 years, those with hormone receptor (HR)-negative status, and those with clinical stage T2, the pCR rate of the TCbHP×6 regimen was significantly higher than the THP×6 regimen (P < 0.05). The TCbHP×6 cohort reported higher frequencies of any-grade adverse events (99% versus 86.7%) and grade 3-4 events (49.5% versus 12%) than the THP×6 cohort. Propensity score matching identified 27 patient pairs between the THP×6 and THP×4 cohorts, indicating a significantly higher pCR rate for the THP×6 regimen than the THP×4 regimen (63% versus 29.6%, P = 0.029). CONCLUSIONS: The TCbHP×6 regimen is favored for individuals aged ≤ 50 years and those aged > 50, ≤60 years with HR-negative status or clinical stage T2-4. For patients in compromised general condition or lacking the specified indications, the THP×6 regimen emerges as a lower-toxicity alternative with satisfactory efficacy. To ensure treatment efficacy, a minimum of 6 cycles of neoadjuvant THP is required.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Carboplatino , Terapia Neoadyuvante , Receptor ErbB-2 , Taxoides , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Terapia Neoadyuvante/métodos , Carboplatino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptor ErbB-2/metabolismo , Persona de Mediana Edad , China/epidemiología , Adulto , Taxoides/administración & dosificación , Estudios de Seguimiento , Trastuzumab/administración & dosificación , Trastuzumab/uso terapéutico , Pronóstico , Estudios Retrospectivos , Anciano , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificaciónRESUMEN
The therapeutic approach to many solid tumors, including non-small cell lung cancer (NSCLC), is mainly based on the use of platinum-containing anticancer agents and is often characterized by acquired or intrinsic resistance to the drug. Therefore, the search for safer and more effective drugs is still an open challenge. Two organometallic ruthenium(II) cyclopentadienyl compounds [Ru(η5-C5H4CHO)(Me2bipy)(PPh3)]+ (RT150) and [Ru(η5-C5H4CH2OH)(Me2bipy) (PPh3)][CF3SO3] (RT151) were tested against a panel of cisplatin-resistant NSCLC cell lines and xenografts. They were more effective than cisplatin in inducing oxidative stress and DNA damage, affecting the cell cycle and causing apoptosis. Importantly, they were found to be inhibitors of drug efflux transporters. Due to this property, the compounds significantly increased the retention and cytotoxicity of cisplatin within NSCLC cells. Notably, they did not display high toxicity in vitro against non-transformed cells (red blood cells, fibroblasts, bronchial epithelial cells, cardiomyocytes, and endothelial cells). Both compounds induced vasorelaxation and reduced endothelial cell migration, suggesting potential anti-angiogenic properties. RT151 confirmed its efficacy against NSCLC xenografts resistant to cisplatin. Either alone or combined with low doses of cisplatin, RT151 showed a good biodistribution profile in the liver, kidney, spleen, lung, and tumor. Hematochemical analysis and post-mortem organ pathology confirmed the safety of the compound in vivo, also when combined with cisplatin. To sum up, we have confirmed the effectiveness of a novel class of drugs against cisplatin-resistant NSCLC. Additionally, they have a good biocompatibility and safety profile.
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OBJECTIVE: To determine the clinical significance of performing repeated postchemotherapy CBC for cancer-bearing dogs receiving ≥ 4 carboplatin treatments. The secondary aim was to identify risk factors associated with cumulative carboplatin-induced neutropenia in those dogs. ANIMALS: 40 client-owned dogs diagnosed with cancer. METHODS: A retrospective study using medical records from a single academic institution during 2012 to 2023. Dogs that received ≥ 4 doses of carboplatin with pre- and postchemotherapy CBCs available were included. Signalment and possible risk factors were recorded. Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events was used for neutropenia grading. RESULTS: 40 dogs met the inclusion criteria, with a total of 206 prechemotherapy and 188 postchemotherapy CBC results available. The median carboplatin dosage was 300 mg/m2 (range, 200 to 300 mg/m2). The median interval between carboplatin administration and the postchemotherapy CBC was 10 days (range, 6 to 38 days). Eleven dogs developed a grade 2 or higher neutropenia, with 5 dogs developing multiple neutropenic events, for a total of 18 separate events (18/394). Only 2 of 18 neutropenic events were recorded at the 10- to 14-day postchemotherapy CBC. The yield of detecting neutropenia at a postchemotherapy CBC at any carboplatin chemotherapy after the second dose was < 1% (1/149). Dogs that developed neutropenia at the pre-2nd chemotherapy CBC had a significantly higher risk of developing another neutropenic event at subsequent prechemotherapy CBC (P < .001). CLINICAL RELEVANCE: The incidence of cumulative neutropenia after 4 to 6 doses of carboplatin is low in cancer-bearing dogs. If a grade 2 or higher neutropenia is observed at or before the second prechemotherapy CBC, the dog is at a higher risk of developing neutropenia following future treatments.
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Radical cystectomy is the standard treatment for muscle-invasive bladder cancer, and pre-surgical treatment can improve survival. Carboplatin and gemcitabine chemotherapy is considered an effective, safe treatment for patients ineligible for cisplatin-based chemotherapy owing to reduced renal function. However, there is limited evidence on pre-surgical treatment with carboplatin and gemcitabine chemotherapy with glomerular filtration rates < 30 mL/min. We discuss the treatment of a patient who did not undergo surgery owing to bladder tumor size of 12 cm (cT3bN0M1a) and severe renal dysfunction (serum creatinine: 2.57 mg/dL, estimated glomerular filtration rate: 20.2 mL/min/1.73 m2). After the patient received two courses of carboplatin and gemcitabine chemotherapy, the bladder tumor size had reduced by 60%. No nausea or renal dysfunction was observed; febrile neutropenia improved with antibiotic therapy and granulocyte colony-stimulating factor. Then, he could undergo robot-assisted radical cystectomy after the pre-surgical chemotherapy treatment. Pre-surgical treatment with carboplatin and gemcitabine chemotherapy is a viable treatment option for patients with muscle-invasive bladder cancer and severe renal dysfunction.
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The high mortality rate due to chemoresistance in patients with high-grade ovarian cancer (HGSOC) emphasizes the urgent need to determine optimal treatment strategies for advanced and recurrent cases. Our study investigates the interplay between estrogens and chemoresistance in HGSOC and shows clear differences between platinum-sensitive and -resistant tumors. Through comprehensive transcriptome analyzes, we uncover differences in the expression of genes of estrogen biosynthesis, metabolism, transport and action underlying platinum resistance in different tissues of HGSOC subtypes and in six HGSOC cell lines. Furthermore, we identify genes involved in estrogen biosynthesis and metabolism as prognostic biomarkers for HGSOC. Additionally, our study elucidates different patterns of estrogen formation/metabolism and their effects on cell proliferation between six HGSOC cell lines with different platinum sensitivity. These results emphasize the dynamic interplay between estrogens and HGSOC chemoresistance. In particular, targeting the activity of steroid sulfatase (STS) proves to be a promising therapeutic approach with potential efficacy in limiting estrogen-driven cell proliferation. Our study reveals potential prognostic markers as well as identifies novel therapeutic targets that show promise for overcoming resistance and improving treatment outcomes in HGSOC.
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Proliferación Celular , Resistencia a Antineoplásicos , Estrógenos , Neoplasias Ováricas , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/genética , Estrógenos/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Clasificación del Tumor , Regulación Neoplásica de la Expresión Génica , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/genética , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Platino (Metal)/farmacología , Platino (Metal)/uso terapéuticoRESUMEN
Background: Ovarian cancer is the leading cause of mortality among gynecological malignancies. Carboplatin and poly (ADP-ribose) polymerase inhibitors (PARPi) are often implemented in the treatment of ovarian cancer. Homologous recombination deficient (HRD) tumors demonstrate increased sensitivity to these treatments; however, many ovarian cancer patients are homologous recombination proficient (HRP). TTFields are non-invasive electric fields that induce an HRD-like phenotype in various cancer types. The current study aimed to investigate the impact of TTFields applied together with carboplatin or PARPi (olaparib or niraparib) in preclinical ovarian cancer models. Methods: A2780 (HRP), OVCAR3 (HRD), and A2780cis (platinum-resistant) human ovarian cancer cells were treated in vitro with TTFields (1 V/cm RMS, 200 kHz, 72 h), alone or with various drug concentrations. Treated cells were measured for cell count, colony formation, apoptosis, DNA damage, expression of DNA repair proteins, and cell cycle. In vivo, ID8-fLuc (HRP) ovarian cancer cells were inoculated intraperitoneally to C57BL/6 mice, which were then treated with either sham, TTFields (200 kHz), olaparib (50 mg/kg), or TTFields plus olaparib; over a period of four weeks. Tumor growth was analyzed using bioluminescent imaging at treatment cessation; and survival analysis was performed. Results: The nature of TTFields-drug interaction was dependent on the drug's underlying mechanism of action and on the genetic background of the cells, with synergistic interactions between TTFields and carboplatin or PARPi seen in HRP and resistant cells. Treated cells demonstrated elevated levels of DNA damage, accompanied by G2/M arrest, and induction of an HRD-like phenotype. In the tumor-bearing mice, TTFields and olaparib co-treatment resulted in reduced tumor volume and a survival benefit relative to olaparib monotherapy and to control. Conclusion: By inducing an HRD-like phenotype, TTFields sensitize HRP and resistant ovarian cancer cells to treatment with carboplatin or PARPi, potentially mitigating a-priori and de novo drug resistance, a major limitation in ovarian cancer treatment.
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BACKGROUND: Patients with extensive-stage small-cell lung cancer (ES-SCLC) have a poor prognosis. The standard palliative treatment for four decades has been chemotherapy as a combination of etoposide with carboplatin or cisplatin, and in recent years, immunotherapy in addition. AIMS: To determine whether there is a difference in the efficacy of palliative chemotherapy as cisplatin or carboplatin in combination with etoposide in patients with ES-SCLC in real-world practice in the Czech Republic. METHODS: This was a retrospective analysis of a cohort of 348 patients from the LUCAS project with ES-SCLC. 79 were treated with etoposide plus cisplatin and 265 were treated with etoposide plus carboplatin. Kaplan-Meier curves and the Cox regression model were used for analysis. RESULTS: No statistically significant difference in median overall survival (mOS) or median progression free survival (mPFS) was found between groups or between patients grouped according to age and performance status (PS) in mOS. The Cox regression result was similar. CONCLUSION: This study shows that cisplatin and carboplatin do not differ in efficacy in a given indication, thus when choosing a treatment, the physician should consider the expected toxicity in a particular patient, assessing the patient's general condition and comorbidities.
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NRF2 activation protects epithelial cells from malignancy, but cancer cells can upregulate the pathway to promote survival. NRF2 activators including CDDO-Methyl ester (CDDO-Me) inhibit cancer in preclinical models, suggesting NRF2 activation in other cell types may promote anti-tumor activity. However, the immunomodulatory effects of NRF2 activation remain poorly understood in the context of cancer. To test CDDO-Me in a murine model of established lung cancer, tumor-bearing wildtype (WT) and Nrf2 knockout (KO) mice were treated with 50-100 mg CDDO-Me/kg diet, alone or combined with carboplatin/paclitaxel (C/P) for 8-12 weeks. CDDO-Me decreased tumor burden in an Nrf2-dependent manner. The combination of CDDO-Me plus C/P was significantly (p < 0.05) more effective than either drug alone, reducing tumor burden by 84% in WT mice. CDDO-Me reduced the histopathological grade of WT tumors, with a significantly (p < 0.05) higher proportion of low-grade tumors and a lower proportion of high-grade tumors. These changes were augmented by combination with C/P. CDDO-Me also protected WT mice from C/P-induced toxicity and improved macrophage and T cell phenotypes in WT mice, reducing the expression of CD206 and PD-L1 on macrophages, decreasing immunosuppressive FoxP3+ CD4+ T cells, and increasing activation of CD8+ T cells in a Nrf2-dependent manner.
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Enhanced drug resistance poses a significant challenge in treating ovarian cancer (OC). Phenylethyl isothiocyanate (PEITC) is involved in drug resistance in OC, but the mechanism remains unclear. In this study, we investigated the molecular regulatory mechanism of carboplatin sensitivity in OC associated with PEITC, MAF BZIP Transcription Factor F (MAFF), and Zinc finger proteins (ZNF) 711. The carboplatin sensitivity was significantly increased in OC cells after PEITC treatment. Knockdown of MAFF significantly enhanced the carboplatin sensitivity of OC cells, promoted apoptosis, inhibited colony-forming efficiency in vitro, and suppressed tumor growth in vivo. The binding site of MAFF to the ZNF711 promoter was predicted, and the knockdown of MAFF significantly increased the ZNF711 expression. Results of the dual luciferase assay and ChIP-PCR confirmed the binding of MAFF to the ZNF711 promoter. Immunofluorescence and CoIP results demonstrated the colocalization and the binding of MAFF and its interacting protein, BZIP Transcription Factor ATF-like 3 (BATF3). Similarly, we confirmed the binding of BATF3 to the ZNF711 promoter. Knockdown of BATF3 alone and simultaneous knockdown of BATF3 and MAFF showed similar regulatory effects on ZNF711 transcription and apoptosis. These suggested that the binding of MAFF to BATF3 inhibited ZNF711 transcription and reduced carboplatin sensitivity in OC.
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Carboplatino , Isotiocianatos , Neoplasias Ováricas , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/genética , Carboplatino/farmacología , Línea Celular Tumoral , Animales , Isotiocianatos/farmacología , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Ratones , Regiones Promotoras Genéticas , Ratones Desnudos , Resistencia a Antineoplásicos/efectos de los fármacos , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Ratones Endogámicos BALB CRESUMEN
PURPOSE: The neoadjuvant chemotherapy (NACT) regimen for triple negative breast cancer (TNBC) primarily consists of anthracyclines and taxanes, and the addition of platinum-based drugs can further enhance the efficacy. However, it is also accompanied by more adverse events, and considering the potential severe and irreversible toxicity of anthracyclines, an increasing number of studies are exploring nonanthracycline regimens that combine taxanes and platinum-based drugs. METHODS: The retrospective study included 273 stage II-III TNBC patients who received NACT. The AT group, consisting of 195 (71.4%) patients, received a combination of anthracyclines and taxanes, while the TCb group, consisting of 78 (28.6%) patients, received a combination of taxanes and carboplatin. Logistic regression analysis was performed to evaluate the factors influencing pathological complete response (pCR) and residual cancer burden (RCB). The log-rank test was used to assess the differences in event-free survival (EFS) and overall survival (OS) among the different treatment groups. Cox regression analysis was conducted to evaluate the factors influencing EFS and OS. RESULTS: After NACT and surgery, the TCb group had a higher rate of pCR at 44.9%, as compared to the AT group at 31.3%. The difference between the two groups was 13.6% (OR = 0.559, 95% CI 0.326-0.959, P = 0.035). The TCb group had a 57.7% rate of RCB 0-1, which was higher than the AT group's rate of 42.6%. The difference between the two groups was 15.1% (OR = 0.543, 95% CI 0.319-0.925, P = 0.024), With a median follow-up time of 40 months, the TCb group had better EFS (log-rank, P = 0.014) and OS (log-rank, P = 0.040) as compared to the AT group. Clinical TNM stage and RCB grade were identified as independent factors influencing EFS and OS, while treatment group was identified as an independent factor influencing EFS, with a close-to-significant impact on OS. CONCLUSION: In stage II-III triple TNBC patients, the NACT regimen combining taxanes and carboplatin yields higher rates of pCR and significant improvements in EFS and OS as compared to the regimen combining anthracyclines and taxanes.
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Antraciclinas , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatino , Terapia Neoadyuvante , Taxoides , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Femenino , Estudios Retrospectivos , Carboplatino/administración & dosificación , Antraciclinas/administración & dosificación , Antraciclinas/uso terapéutico , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto , Taxoides/administración & dosificación , Taxoides/uso terapéutico , Anciano , Estadificación de NeoplasiasRESUMEN
Background: Acute cardiac complications post-chemotherapy is rare. Stress cardiomyopathy, one of these complications, should be considered in differential diagnoses as its symptoms closely resemble those of acute myocardial infarction and can lead to mortality. Objective: The objective of this paper is to describe Takotsubo syndrome (TTS) as an acute complication following combined chemotherapy in a patient with significant thromboembolic burden and metastatic cervical cancer. Case: A 61-year-old female patient with a diagnosis of metastatic cervical cancer experienced acute chest pain. Elevated troponin levels and abnormalities in the electrocardiogram initially suggested an acute myocardial infarction, occurring after a chemotherapy session involving Carboplatin and Paclitaxel infusion. Although initial treatment targeted myocardial infarction, further diagnostic evaluations including coronary angiography and cardiac magnetic resonance imaging revealed no coronary artery disease but identified features consistent with stress cardiomyopathy, indicative of Takotsubo syndrome (TTS). This diagnosis led to an improvement in symptoms and a resolution of the acute changes observed. Conclusion: Stress cardiomyopathy, particularly TTS, is being increasingly recognized as an acute complication associated with combined chemotherapy regimens. The potential cardiotoxic effects of these chemotherapy agents demand careful monitoring and evaluation in patients undergoing oncological treatment, underscoring the importance of integrating cardioprotective strategies into the management of these patients.
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BACKGROUND/AIM: In recent years, switch maintenance after platinum-based chemotherapy has been a standard of care. However, the appropriate number of systemic chemotherapy cycles against advanced-stage urothelial carcinoma (UC) remains unclear. This study assessed the survival outcomes of first-line platinum-based chemotherapy according to treatment cycles in patients with metastatic disease. PATIENTS AND METHODS: We retrospectively evaluated patients with metastatic bladder and upper urinary tract cancer who received platinum-based combination therapy. Overall survival (OS) was evaluated using the Kaplan-Meier method and the log-rank test. RESULTS: Of 179 patients, 47 (26.3%) were women, and 73 (40.8%) had upper urinary tract cancer. Furthermore, 47 (26.3%) who were not eligible for cisplatin received carboplatin. The median number of treatment cycles was 3 (range=1-14 cycles). The rates of progressive disease within two cycles, from two to four cycles, and from four to six cycles were 18.4%, 19.2%, and 30.6%, respectively. The median OS of patients with 2, 3, 4, 5-6, and ≥7 treatment cycles were 8.6, 14.3, 21.3, 24.4, and 26.1 months, respectively. The OS did not significantly differ between patients receiving four treatment cycles and those receiving ≥5 treatment cycles. In patients with disease control (complete or partial response or stable disease) receiving ≥4 treatment cycles, there was no significant difference in terms of OS between patients receiving four cycles and those receiving six cycles. CONCLUSION: Four cycles of first-line platinum-based chemotherapy can be effective in patients with metastatic UC.
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Protocolos de Quimioterapia Combinada Antineoplásica , Metástasis de la Neoplasia , Humanos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano de 80 o más Años , Adulto , Resultado del Tratamiento , Platino (Metal)/uso terapéutico , Estudios Retrospectivos , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/mortalidad , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patología , Neoplasias Urológicas/mortalidad , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Estimación de Kaplan-Meier , Estadificación de Neoplasias , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Cisplatino/uso terapéutico , Cisplatino/administración & dosificaciónRESUMEN
Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in addition to a 5-hydroxytryptamine type 3 receptor antagonist with dexamethasone (DEX) for CBDCA-containing chemotherapy because of its higher emetogenic risk. However, the additional efficacy of aprepitant (APR) in CBDCA-containing treatment remains controversial, and data on multiple-day treatments are limited. Etoposide (ETP) was administered on days 1-3 in the CBDCA + ETP regimen, and it is important to evaluate suitable antiemetic therapy for the regimen. Therefore, we evaluated the efficacy of additional APR in CBDCA + ETP. Patients were divided into two groups and retrospectively evaluated. One was the control group, which was prophylactically administered palonosetron (PALO) and DEX, and the other was the APR group, which received APR orally with PALO and DEX. The primary endpoint was complete response (CR) between the groups. The overall CR rates were 75.0 and 76.4% in the control and APR groups, respectively, with no significant difference (p = 1.00). In the acute phase, it was 88.9 and 97.2%, respectively, and 86.1 and 79.2% in the delayed phase, respectively, without significant differences (p = 0.10 and 0.38, respectively). The incidence and severity of nausea, vomiting, and anorexia were not significantly different between the two groups in the acute and delayed phases. Our findings suggest that combining APR with PALO and DEX does not improve the CR rate in CBDCA + ETP therapy.
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Antieméticos , Aprepitant , Carboplatino , Dexametasona , Etopósido , Náusea , Palonosetrón , Vómitos , Aprepitant/uso terapéutico , Aprepitant/administración & dosificación , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Carboplatino/efectos adversos , Humanos , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Palonosetrón/administración & dosificación , Palonosetrón/uso terapéutico , Masculino , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Antieméticos/administración & dosificación , Antieméticos/uso terapéutico , Femenino , Persona de Mediana Edad , Vómitos/inducido químicamente , Vómitos/prevención & control , Anciano , Náusea/inducido químicamente , Náusea/prevención & control , Estudios Retrospectivos , Adulto , Quimioterapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quinuclidinas/administración & dosificación , Quinuclidinas/uso terapéutico , Morfolinas/administración & dosificación , Morfolinas/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Isoquinolinas/administración & dosificación , Isoquinolinas/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVES: Lactate dehydrogenase A (LDH-A) catalyzes the last step of glycolysis: supplying cells rapidly but inefficiently with ATP. Many tumors, including malignant mesothelioma (MM), have a high expression of LDH-A, which is associated with cancer aggressiveness. We aimed to determine whether the efficacy of the gemcitabine/carboplatin (Gem + Carbo) combination, widely used to treat this disease, could be increased by inhibition of LDH-A (by NHI-2). To this aim, we analyzed the growth inhibition of pleural and peritoneal MM by multiple combinations. METHODS: The 72 h sulforhodamine B assay (SRB) was used to test the cytotoxicity of the combination of gemcitabine (in the range 0.1 - 400 nM) and carboplatin (0.01 - 40 µM) with a fixed concentration of NHI-2 (at IC25). We used pleural (H2452) and primary peritoneal (STO, MESO-II) MM cell lines, cultured at normoxic conditions. RESULTS: NHI-2 did not increase the cytotoxicity of the combination of 100 nM gemcitabine and 10 µM carboplatin in peritoneal MM cell lines. The cell growth inhibition was 10% smaller after the triple combination than the Gem + Carbo treatment. CONCLUSIONS: Inhibition of LDH-A did not increase the efficacy of gemcitabine and carboplatin in MM under normoxic conditions.
RESUMEN
OBJECTIVE: Lung cancer is the most common malignancy and among the leading cause of cancer death worldwide. Therefore, there is an important need for biomarkers that can be used in the early diagnosis of the disease and in the follow-up of treatment. Circular RNAs (circRNAs) have a covalently closed circular structure that lacks 3' and 5' polar ends and is resistant to RNAase enzymes. Due to these properties, they can be stably found in body fluids. Therefore, they can serve as potential biomarkers in the diagnosis, monitoring of therapeutic response and prognosis of cancer. In our study, we aimed to investigate the expression levels of circRNA molecules in the treatment of lung cancer and to determine those that have the potential to be biomarkers. METHODS: In this in vitro study, expression levels of 163 circRNAs were investigated in A549 cells, a non-small cell lung cancer cell line, before and after treatment with carboplatin and pemetrexed. Total RNA isolation and cDNA synthesis were performed after treatments. Expression levels of circRNA genes were determined by RT-qPCR method with the designed divergent primer sequences. RESULTS: The study revealed the characterisation of differentially expressed circRNAs by treatment in lung cancer cells. Of them, hsa_circ_0001320 is not expressed in cancer cells, is expressed only after treatment, and increased the level of its expression in response to combination therapy. CONCLUSION: As a result, while carboplatin, pemetrexed, and combined drug applications changed the expression levels of some circRNAs in lung cancer cells, some circRNAs were expressed only after treatment. In treatment follow-up and management, hsa_circ_0001320 has been identified as potential biomarker candidate.
Asunto(s)
Biomarcadores de Tumor , Neoplasias Pulmonares , ARN Circular , Humanos , ARN Circular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Biomarcadores de Tumor/genética , Pronóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carboplatino/uso terapéutico , Pemetrexed/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Células Tumorales CultivadasRESUMEN
Background: Platinum-based combination chemotherapy, including cisplatin and carboplatin, are important cytotoxic anti-cancer agents that are widely used to treat various solid tumors. Carboplatin has a similar effect on survival in small cell lung cancer, but generally has a milder toxicity profile when compared with cisplatin. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity from carboplatin is rarely reported. Case presentation: A 79-year-old man underwent intravenous polychemotherapy (atezolizumab, etoposide, and carboplatin) for small cell lung cancer. One week after the second cycle of chemotherapy, he reported bilateral visual loss as hand motion in both eyes. Dilated fundus examination showed retinal arterial narrowing without hemorrhage, and diffuse choroidal and retinal thinning was observed in an optical coherence tomography scan. Fluorescein angiography revealed significantly delayed circulation without evidence of obstructive lesions. 30-Flicker electroretinogram testing showed a complete absence of cone response in both eyes. The patient's visual acuity aggravated to no light perception in both eyes, even after the cessation of chemotherapy. Conclusions: Carboplatin combination chemotherapy administered at therapeutic doses can result in irreversible visual loss, a side effect that is not widely acknowledged. When using carboplatin, physicians should be aware of its potential ocular toxicity.
Asunto(s)
Carboplatino , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carboplatino/uso terapéutico , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Masculino , Anciano , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trastornos de la Visión/inducido químicamente , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificaciónRESUMEN
BACKGROUND: Despite treatment having improved through intensive surgical procedures and chemotherapy-and more recently, targeted therapies-ovarian cancer is the most fatal female cancer. As such, we wanted to analyze age-specific survival trends for ovarian cancer in Denmark, Finland, Norway and Sweden over the past 50 years, with a special aim of comparing survival development between the age groups. METHODS: We modelled survival data from the NORDCAN database for 1-, 5- and conditional 5/1-year relative (between years 1 and 5) survival for ovarian cancer from 1972 to 2021. RESULTS: Young patients had a 70% 5-year survival while the survival was only 30% for the oldest patients. Conditional survival showed that survival between years 1 and 5 did not improve for patients older than 60 years throughout the 50-year period, during which time the gaps between the youngest and the oldest patients widened. CONCLUSIONS: Improvement in 1-year survival was so large that it masked the modest development between years 1 and 5, resulting in a widening age disparity in 5-year survival. The current treatment practices, which appear increasingly effective for younger patients, have not helped remedy the large age differences in ovarian cancer survival. Early detection methods and therapeutic innovations are urgently needed, and aged patients need a special focus.