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BACKGROUND: The therapeutic benefit of concurrent chemoradiotherapy (CCRT) in elderly nasopharyngeal carcinoma (NPC) patients remains controversial. This study aimed to investigate the efficacy and toxicity of lobaplatin-based CCRT in elderly patients with NPC. METHODS: We included stage II-IVA NPC patients aged ≥65 years who received lobaplatin concomitant with intensity-modulated radiation therapy (IMRT) between March 2019 and January 2023. Objective response rates and treatment-related toxicity were assessed. Kaplan-Meier's analysis was performed to calculate survival rates. RESULTS: A total of 29 patients were included with a median age of 67 years. There were 19 patients (65.5%) who had comorbidities. All patients had serum EBV-DNA detective before treatment; the median EBV-DNA load was 236 IU/mL. There were 25 (86.2%) patients treated with induction chemotherapy, and the overall response rate was 92.0%. All patients received IMRT and concurrent chemotherapy with lobaplatin. During the CCRT, the most common adverse effect was haematological toxicity. Three patients (10.3%) had grade 3 leucopenia, three patients (10.3%) had grade 3 neutropenia, and eight patients (27.6%) had grade 3-4 thrombocytopenia. The rate of grade 3 mucositis was 34.5%. No patients had liver and kidney dysfunction. The median weight loss was 4 kg during CCRT. After three months of CCRT, the total response rate was 100%. EBV-DNA was not detected in any patients. The median follow-up was 32.1 months. The 3-year locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival and overall survival were 95.8%, 85.7%, 82.5% and 100%, respectively. CONCLUSIONS: Lobaplatin-based CCRT is safe and feasible for elderly NPC patients, with satisfactory short-term survival outcomes and acceptable toxicities. A phase 2 trial is ongoing to investigate the role of lobaplatin-based CCRT on long-term survival and treatment toxicities for this population.

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Quimioradioterapia , Ciclobutanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Compuestos Organoplatinos , Radioterapia de Intensidad Modulada , Humanos , Masculino , Anciano , Femenino , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Ciclobutanos/uso terapéutico , Ciclobutanos/administración & dosificación , Ciclobutanos/efectos adversos , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/tratamiento farmacológico , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Estimación de Kaplan-Meier

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BACKGROUND: This study evaluated the safety and efficiency of intraperitoneal irrigation chemotherapy with lobaplatin for the treatment of advanced gastric cancer (GC). METHODS: A total of 56 locally advanced GC patients (experimental group) who received intraoperative intraperitoneal irrigation chemotherapy in addition to undergoing radical D2 surgery were matched 1:1 based on 8 covariates to 56 patients without drug treatment (control group). Clinical data were collected and analyzed. RESULT: The two groups were well balanced in basic characteristics and had comparable clinical indices. All patients had similar time to first flatus (2.8 ± 0.3 vs. 2.9 ± 0.3 d, P = 0.076), time to first oral intake (3.5 ± 3.4 vs. 4.1 ± 4.6 d, P = 0.439), and duration of postoperative hospitalization (9.1 ± 3.2 vs. 9.6 ± 4.0 d, P = 0.446). There were no significant differences in postoperative complications including anastomotic and duodenal stump leakage, abdominal and anastomotic bleeding, seroperitoneum, and incision infection between the experimental and control groups (P > 0.05). The rates of chemotherapy-related side effects including allergic reaction, neurotoxicity, diarrhea, and nausea/vomiting were also similar between the two groups, and there were no abnormalities in leukocyte and platelet levels and liver and renal function during the first 5 days after surgery. CONCLUSION: Intraperitoneal irrigation chemotherapy with lobaplatin is safe for patients with advanced gastric cancer.

Asunto(s)

Ciclobutanos , Compuestos Organoplatinos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Ciclobutanos/administración & dosificación , Lavado Peritoneal/métodos , Pronóstico , Estudios de Casos y Controles , Estudios de Seguimiento , Anciano , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Adulto , Irrigación Terapéutica/métodos

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Lobaplatin shows antitumor activity against a wide range of tumors, including triple-negative breast cancer (TNBC), and has been linked to cancer stem cell pool. Here, we investigated the molecular mechanisms behind lobaplatin resistance and stemness in vitro and in vivo. Two chemoresistance-related GEO data sets (GSE70690 and GSE103115) were included to screen out relevant genes. Cysteine-rich secretory protein 3 (CRISP3) was found to be overexpressed in lobaplatin-resistant TNBC and related to poor diagnosis. CRISP3 expression was significantly correlated with tumor stemness markers in lobaplatin-resistant cells. E1A-associated protein p300 (EP300) regulated CRISP3 expression by affecting the H3K27ac modification of the CRISP3 promoter. In addition, knocking down EP300 curbed the malignant biological behavior of lobaplatin-resistant cells, which was antagonized by CRISP3 overexpression. Collectively, our results highlight the EP300/CRISP3 axis as a key driver of lobaplatin resistance in TNBC and suggest that therapeutic targeting of this axis may be an effective strategy for enhancing platinum sensitivity in TNBC.

Asunto(s)

Antineoplásicos , Resistencia a Antineoplásicos , Proteína p300 Asociada a E1A , Epigénesis Genética , Células Madre Neoplásicas , Proteínas y Péptidos Salivales , Proteínas de Plasma Seminal , Neoplasias de la Mama Triple Negativas , Femenino , Humanos , Antineoplásicos/farmacología , Línea Celular Tumoral , Ciclobutanos , Resistencia a Antineoplásicos/genética , Proteína p300 Asociada a E1A/genética , Proteína p300 Asociada a E1A/metabolismo , Epigénesis Genética/genética , Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Compuestos Organoplatinos/farmacología , Proteínas de Plasma Seminal/genética , Proteínas de Plasma Seminal/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Proteínas y Péptidos Salivales/genética , Proteínas y Péptidos Salivales/metabolismo

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BACKGROUND: Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline. METHODS: We randomly allocated patients with stage I-III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety. RESULTS: A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs. 21.2%, P = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR (Pinteraction = 0.001, Pinteraction = 0.012, respectively). There was no significant difference in EFS (P = 0.895) or OS (P = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A (P = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B (P = 0.044). CONCLUSIONS: Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future.

Asunto(s)

Antraciclinas , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclobutanos , Terapia Neoadyuvante , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclobutanos/administración & dosificación , Ciclobutanos/uso terapéutico , Antraciclinas/uso terapéutico , Antraciclinas/administración & dosificación , Anciano , Taxoides/uso terapéutico , Taxoides/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Resultado del Tratamiento , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Hidrocarburos Aromáticos con Puentes

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INTRODUCTION: Gastric cancer (GC) is the third largest cause of cancer-related death worldwide, with major geographic disparities in incidence and outcomes. Sociodemographic indicators, food habits, and genetic predispositions all add to the load. Despite advances in systemic treatments, peritoneal metastasis remains a concern, with intraperitoneal chemotherapy (IPC) emerging as a promising treatment option. METHODS: A prospective cohort research was done, with 30 GC patients receiving cytoreductive surgery (CRS) followed by lobaplatin-based intraoperative chemotherapy. The study evaluated postoperative complications, survival rates, and disease recurrence using Statistical Package for the Social Sciences (SPSS) version 25.0 (IBM SPSS Statistics, Armonk, NY) for data analysis. The purpose of this study is to assess the effectiveness, safety, and dependability of lobaplatin as an intraoperative chemotherapeutic agent in patients having gastric cancer surgery, with a particular emphasis on those patients who do not have distant metastases. RESULTS: The study population had a balanced gender distribution, with an average age of 44.83 years. Most patients had advanced-stage cancer (T3 and T4), and lobaplatin treatment resulted in a low frequency of serious postoperative sequelae. Preliminary studies suggest that lobaplatin is a safe and potentially effective IPC drug for GC, with few side effects and adequate survival rates. CONCLUSION: Lobaplatin shows promise as an intraoperative chemotherapeutic treatment for gastric cancer, necessitating more research in bigger, randomized controlled studies to determine its efficacy and safety profile. The study emphasizes the need for novel treatment strategies to enhance the prognosis of GC patients, particularly those with peritoneal involvement.

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Objective: Ramucirumab is a VEGFR2 antagonist. The aim of this trial is to evaluate the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer. Methods: and analysis: This study is a prospective single-center, randomized controlled and open label clinical study, enrolling a total of 140 patients with advanced gastric cancer distributed across two distinct cohorts (Cohort A n = 70; Cohort B n = 70). The central focus of the study lies in evaluating the pathological complete response (pCR) of the cancer post-neoadjuvant or conversion therapy. Secondary endpoints encompass the assessment of the R0 resection rate subsequent to the aforementioned therapies, the occurrence of adverse events (AE), progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the total response rate and its duration, the disease control rate (DCR), and the duration of overall response (DOR). Ethics: Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Air force Military Medical University (KY20232220-F-1). Trial registration: This trial has been registered at the ClinicalTrials.gov: NCT06169410 (registration date: December 5, 2023).

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BACKGROUND: Our previous work indicated that the addition of lobaplatin to combined therapy with taxane and anthracycline can improve the pathological complete response rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are unclear. METHODS: Eighty-three patients who met the inclusion criteria were included in this post hoc analysis. We analyzed the association between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before neoadjuvant chemotherapy with the efficacy and prognosis after treatment with docetaxel, epirubicin, and lobaplatin neoadjuvant chemotherapy regimen. χ2 test and Cox regression were used to analyze the association between PLR and NLR with total pathologic complete response (tpCR), as well as the association between PLR and NLR with event-free survival (EFS) and overall survival (OS), respectively. RESULTS: The tpCR rate in the PLR- group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% [8/32], P = .032). The tpCR rate in the NLR- group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% [7/30], P = .024). The tpCR rate of the PLR-NLR- (PLR- and NLR-) group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ (PLR+ or/and NLR+) group (26.1% [11/42]; P = .012). EFS and OS in the NLR+ group were significantly shorter than those in the NLR- group (P = .028 for EFS; P = .047 for OS). Patients in the PLR-NLR- group had a longer EFS than those in the PLR+/NLR+ group (P = .002). CONCLUSION: PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with the taxane, anthracycline, and lobaplatin regimen for patients with TNBC, as patients who had lower PLR and NLR values had a higher tpCR rate and a better long-term prognosis.

Asunto(s)

Ciclobutanos , Terapia Neoadyuvante , Compuestos Organoplatinos , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/sangre , Neoplasias de la Mama Triple Negativas/mortalidad , Femenino , Terapia Neoadyuvante/métodos , Pronóstico , Persona de Mediana Edad , Ciclobutanos/farmacología , Ciclobutanos/uso terapéutico , Ciclobutanos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/farmacología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Anciano , Neutrófilos/metabolismo , Biomarcadores de Tumor/sangre , Linfocitos/metabolismo , Plaquetas/patología , Estudios Retrospectivos

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PURPOSE: To compare the toxicity and clinical efficacy of TL (docetaxel + lobaplatin) induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy and TPF (docetaxel + cisplatin + 5-fluorouracil) induction chemotherapy combined with cisplatin concurrent chemoradiotherapy in the treatment of locally advanced head and neck squamous cell carcinoma. METHODS AND PATIENTS: In total, 128 patients with locally advanced head and neck cancer were prospectively enrolled between August 2016 and April 2021. They were randomly divided into trial group and control group, all using chronological dosage mode. The trial group used TL regimen induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy; the control group used TPF regimen induction chemotherapy and cisplatin concurrent chemotherapy. The endpoints were adverse events and survival rates at 1, 3 and 5 years. RESULTS: Median follow-up was 42 months (20-71 months). (1) Adverse events: During induction chemotherapy, compared with TPF group, grade 3-4 leukocytes and neutrophils, diarrhea, 1-2 hyperbilirubinemia, nausea / vomiting, oral mucositis, fatigue, anorexia, hyponatremia were significantly lower in TL group (p<0. 05): 6% vs. 35%, 14% vs. 53%, 0% vs. 6%, 15% vs. 40%, 9% vs. 56%, 0% vs. 10%, 3% vs. 13%, 2% vs. 23%, 15% vs. 74%. During chemoradiotherapy, the incidence of hyponatremia, hypokalaemia and grade 1-2 nausea was significantly lower in the TL group (p<0. 05), with 24% vs. 69%, 20% vs. 65% and 24% vs. 44%, respectively. However, more grade 3-4 thrombocytopenia were observed in the TL group (15% vs. 3%, p<0. 05). (2) There was no significant difference in the recent objective response rate (ORR) between patients with TL group and TPF group (p=0.961). (3) There was no statistical difference in 1, 3 and 5 years OS between TL group and TPF group, respectively, (71.0% vs. 67.5%, p=0.573), (56.6% vs. 56.9%, p=0.814), (52.5% vs. 52.9%, p=0.841); 1, 3 and 5 years PFS are: (63.4% vs. 64.0%, p=0.883), (51.1% vs. 54.0%, p=0.705) and (47.3% vs. 45.9%, p=0.887), None of them were significantly different. Multivariate analysis of COX regression showed that T stage (p=0.01) and surgery (p=0.046) were independent factors affecting PFS and OS, respectively. OS subgroup analysis shows that people receiving the TL regimen in postoperative and nodal stage N1 and N2 patients tended to survive longer than those receiving the TPF regimen. CONCLUSION: Patients with postoperative, N1 or N2 stage locally advanced head and neck squamous cell carcinoma (HNSCC) may have more significant clinical benefits when treated with TL regimen. TL regimen has advantages in reducing toxic side effects and can be used as one of the first-line treatment options. TRIAL REGISTRATION: ClinicalTrials.gov (No. NCT03117257).

Asunto(s)

Neoplasias de Cabeza y Cuello , Hiponatremia , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia/métodos , Cisplatino , Docetaxel , Fluorouracilo , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Hiponatremia/inducido químicamente , Hiponatremia/tratamiento farmacológico , Quimioterapia de Inducción/métodos , Náusea/inducido químicamente , Estudios Prospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico

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Background: Lobaplatin (LBP) is a third-generation platinum-based drug that has been approved only in China for the treatment of several cancer types. Nonetheless, its efficacy in treating bladder cancer (BC) is unclear thus far. Through in vitro and in vivo experiments, this study aimed to explore whether LBP has an antitumor effect on T24 and 5637 BC cells and whether the effect is related to B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and regulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. Methods: For in vitro experiments, the cell counting kit-8 (CCK-8) method was used to determine how different concentrations of LBP affect the viability of two types of BC cells. A wound healing assay was used to test the inhibitory effect of LBP on the migration of the two cell lines. Annexin V-fluorescein isothiocyanate isomer I (V-FITC)/propidium iodide (PI) staining was used to detect changes in cell apoptosis before and after LBP treatment, and Western blotting was used to detect the expression of apoptosis-related proteins and PI3K/Akt pathway proteins. For in vivo experiments, a cell-derived xenograft (CDX) model was employed, and the weight of nude mice and the tumor size were measured. Immunohistochemistry was used to detect the effect of LBP on the expression of apoptosis-related proteins in tumor xenografts. Results: In vitro, LBP reduced proliferation (P<0.05), inhibited migration (P<0.05), and induced apoptosis in T24 (31.25%±1.20%, P<0.01) and 5637 (14.3%±2.24%, P<0.05) BC cells, in a dose-dependent manner (P<0.05); increased the expression of proapoptotic proteins, including Bax, caspase-3 and cleaved caspase-3 (P<0.05); and suppressed the expression of antiapoptotic proteins, including Bcl-2, PI3K, Akt and phosphorylated Akt (p-Akt). The in vivo experiment confirmed that LBP can reduce the size of subcutaneous tumors in nude mice (P<0.05), increase the expression levels of Bax and cleaved caspase-3 and lower the expression of Bcl-2 (P<0.05) in bladder tumor tissue. Conclusions: The results obtained from both experiments suggest that LBP can inhibit the proliferation of T24 and 5637 BC cells, which might be credited to its effects in regulating Bcl-2 and Bax expression and inhibiting the PI3K/Akt pathway.

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Background: Patients with gastric cancer have a poor prognosis. Currently, intraperitoneal chemotherapy has been considered a therapeutic option to improve prognosis due to its appealing theoretical rationales. But there is no consensus on the choice of chemotherapeutic agents used in intraperitoneal chemotherapy for gastric cancer. The real-world efficacy of applying intraoperative chemotherapy in gastric cancer still remains undefined. Methods: Patients with gastric cancer who underwent radical gastrectomy at the Gastrointestinal Department of The First Affiliated Hospital of Anhui Medical University between 2012 and 2019 were enrolled in this study. Patients were divided into two groups based on whether they received intraperitoneal chemotherapy. The t-test (mean of two samples) was conducted to compare the difference in measurement data between the two groups, and the chi-square test was used to compare the difference in count data. Kaplan-Meier method with log-rank test was performed to analyze the overall survival of patients. Kaplan-Meier method with log-rank test was also performed in various subgroups to respectively compare the survival of patients. Multivariate Cox analysis was performed to analyze the prognosis factors of these patients. Results: A total of 1253 patients were included in the final analysis, in which 861 patients received intraperitoneal chemotherapy and 352 not received intraperitoneal chemotherapy. The clinicopathological features of the participants in the two groups were comparable. There was no significant difference between the two groups in overall survival (P > 0.05). Consistently, no significant difference was found between the two groups in each subgroup (P > 0.05). The multivariate Cox analysis demonstrated that only age, BMI, pathological type, TNM stage, and differentiation grade were independent risk factors of survival. Conclusion: Intraoperative intraperitoneal chemotherapy usage did not improve survival in patients with gastric cancer undergoing radical gastrectomy.

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Drug resistance is a major obstacle in cancer treatment and recurrence prevention and leads to poor outcomes in patients suffering from osteosarcoma. Clarification of the mechanism of drug resistance and exploration of effective strategies to overcome this obstacle could lead to clinical benefits for these patients. The expression of far upstream element-binding protein 1 (FUBP1) was found to be markedly elevated in osteosarcoma cell lines and clinical specimens compared with osteoblast cells and normal bone specimens. High expression of FUBP1 was correlated with a more aggressive phenotype and a poor prognosis in osteosarcoma patients. We found that overexpression of FUBP1 confers lobaplatin resistance, whereas the inhibition of FUBP1 sensitizes osteosarcoma cells to lobaplatin-induced cytotoxicity both in vivo and in vitro. Chromatin immunoprecipitation-seq and RNA-seq were performed to explore the potential mechanism. It was revealed that FUBP1 could regulate the transcription of prostaglandin E synthase (PTGES) and subsequently activate the arachidonic acid (AA) metabolic pathway, which leads to resistance to lobaplatin. Our investigation provides evidence that FUBP1 is a potential therapeutic target for osteosarcoma patients. Targeting FUBP1, its downstream target PTGES and the AA metabolic pathway may be promising strategies for sensitizing chemoresistant osteosarcoma cells to lobaplatin.

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Objective: To explore the clinical safety and efficacy of single and multiple applications of lobaplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with T4 gastric cancer and to evaluate the impact of HIPEC on peritoneal metastasis. Materials and methods: We retrospectively reviewed prospectively collected data from T4 gastric cancer patients who underwent radical gastric resection plus HIPEC between March 2018 and August 2020 from the National Cancer Center and Huangxing Cancer Hospital. Patients who underwent radical surgery and HIPEC were divided into two groups: the single-HIPEC group (radical resection + a single application of intraoperative HIPEC with lobaplatin 50 mg/m2 at 43.0 ± 0.5°C for 60 min), and a multi-HIPEC group (two more HIPEC applications were performed after radical surgery). Results: A total of 78 patients were enrolled in this two-center study; among them, 40 patients were in the single-HIPEC group, and 38 patients were in the multi-HIPEC group. The baseline characteristics were well balanced between the two groups. There was no significant difference in the postoperative complication rates between the two groups (P > 0.05). Mild renal dysfunction, mild liver dysfunction, low platelet levels and low white blood cell levels were recorded in both groups, without significant differences between the two groups (P > 0.05). After a mean follow-up of 36.8 months, 3 (7.5%) patients in the single-HIPEC group and 2 (5.2%) patients in the multi-HIPEC group experienced peritoneal recurrence (P > 0.05). Both groups had comparable 3-year overall survival (OS) (51.3% vs. 54.5%, P = 0.558) and 3-year disease-free survival (DFS) rates (44.1% vs. 45.7%, P = 0.975). Multivariate analysis showed that an age > 60 years and low preoperative albumin levels were independent risk factors for postoperative complications. Conclusion: Single and multiple applications of HIPEC in patients with T4 gastric cancer were safe and feasible. Both groups had similar postoperative complication rates, 3-year OS rates and 3-year DFS rates. Special attention should be given to HIPEC for patients aged > 60 years and patients with low preoperative albumin levels.

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Objective: To explore the clinical efficacy of lobaplatin-based prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with T4 gastric cancer after surgery and to evaluate its impact on survival. Materials and methods: Data on patients with T4 gastric cancer who underwent radical gastric resection between March 2016 and August 2017 were collected from the National Cancer Center and Huangxing Cancer Hospital. Enrolled patients were divided into two groups according to receiving or not receiving HIPEC. Results: A total of 106 patients were included in this study; among them, 51 patients underwent radical gastric resection plus prophylactic HIPEC, and 55 patients underwent radical gastric resection only. The baseline characteristics were well balanced between the two groups. The postoperative platelet counts in the HIPEC group were significantly lower than those in the non-HIPEC group (P < 0.05); however, we did not observe any occurrences of serious bleeding in the HIPEC group. There were no significant differences in the postoperative complication rates between the two groups (P > 0.05). The postoperative (1 month) CEA, CA19-9, and CA72-4 levels in the HIPEC group were significantly decreased in the HIPEC group (P < 0.05). At a median follow-up of 59.3 months, 3 (5.5%) patients in the HIPEC group experienced peritoneal recurrence, and 10 (18.2%) patients in the non-HIPEC group experienced peritoneal recurrence (P < 0.05). Both groups had comparable 5-year overall survival (OS) rates (41.1% HIPEC group vs. 34.5% non-HIPEC group, P = 0.118). The 5-year disease-free survival was significantly higher in the HIPEC group than in the non-HIPEC group (28.6% versus 39.7%, p = 0.046). Conclusions: Lobaplatin-based prophylactic HIPEC is feasible and safe for patients with T4 gastric cancer and does not increase postoperative adverse effects. The use of HIPEC showed a significant decrease in the incidence of local recurrence rates and blood tumor marker levels. The 5-year disease-free survival was significantly higher in the HIPEC group; however, the 5-year OS benefit was not found in T4 stage patients.

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BACKGROUND: The drug selection of radical surgery (RS), with hyperthermic intraperitoneal chemotherapy (HIPEC), in pT4 colorectal cancer (CRC) remains controversial. METHODS: Adverse events after HIPEC were estimated by common terminology criteria for adverse events version 5.0. The efficacy was evaluated using overall survival (OS) and recurrence-free rate (RFR). Propensity score matching (PSM) was used to reduce the influence of confounders between Mitomycin and Lobaplatin groups. RESULTS: Of the 146 patients, from April 2020 to March 2021, 47 were managed with mitomycin and 99 with lobaplatin. There was no significant difference in the incidence of all adverse events between the two groups after PSM. OS and RFR were not significantly different between the two groups at 22 months (p = 0.410; p = 0.310). OS and RFR of the two groups also showed no significant difference for patients with T4a or T4b stage, tumor size < or ≥ 5 cm. Among patients with colon cancer, RFR at 22 months of the two groups was significantly different (100.0% vs. 63.2%, p = 0.028). CONCLUSIONS: In summary, the safety of mitomycin and lobaplatin for HIPEC was not different. Compared with lobaplatin, mitomycin for HIPEC after RS could benefit patients with colon cancer in RFR.

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Neoplasias del Colon , Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Mitomicina/uso terapéutico , Neoplasias Peritoneales/tratamiento farmacológico , Quimioterapia Intraperitoneal Hipertérmica , Puntaje de Propensión , Terapia Combinada , Neoplasias del Colon/tratamiento farmacológico

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PURPOSE: To investigate the safety and efficacy of lobaplatin-TACE in treating primary hepatocellular carcinoma. METHODS: The data of 536 patients who underwent TACE in the interventional department from January 2016 to January 2020 were collected. Patients were divided into two groups according to the chemotherapeutic drugs used in TACE.: the epirubicin-TACE group (N = 260) and the lobaplatin-TACE group (N = 276). Primary study endpoint: (1) The tumor response after TACE; (2) The survival rates; Secondary study endpoints:(1) Changes in liver function and blood routine before and after TACE; (2) Occurrence of the post-embolization syndrome and infection after TACE. RESULTS: The ORR was 35.0% in the epirubicin-TACE group and 51.1% in the lobaplatin-TACE group (p=0.001). The DCR was 73.1% in the epirubicin-TACE group and 82.2% in the lobaplatin-TACE group (p=0.011). The 6-month, 9- month, 12-month, and 15-month survival rates were higher in the lobaplatin-TACE group than in the epirubicin-TACE group (p=0.029, p=0.001, p=0.005, p=0.002). mOS: Epirubicin-TACE group,14.8 months; Lobaplatin-TACE group,18.6 months (p=0.007). mPFS: Epirubicin-TACE group,9.5 months; Lobaplatin-TACE group,12.8 months (P =0.000). There was no statistical difference in ALT, AST, total bilirubin and Leucocyte after TACE between the two groups (p=0.343, p=0.368, p=0.288, p=0.359). The platelet decrease after TACE was more significant in the lobaplatin- TACE group than in the epirubicin-TACE group (p=0.046). There was no statistical difference in the incidence rate of abdominal pain, fever and infection after TACE between the two groups (p=0.502, p=0.602, p=0.726). The incidence of vomiting after TACE in the lobaplatin-TACE group was higher than that in the epirubicin-TACE group (p=0.003). CONCLUSION: Lobaplatin-TACE has a higher tumor response rate and survival rate. Lobaplatin-TACE is a safe and effective treatment strategy; it is worthy of clinical application.

Asunto(s)

Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Epirrubicina/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

Background: Since lobaplatin (LBP) has been approved to treat metastatic breast cancer in China, this study aimed to evaluate the safety and efficacy of LBP-based chemotherapy in clinical practice. Methods: This trial was a prospective, open-label, multicenter phase IV clinical trial that enrolled patients with unresectable locally advanced or recurrent/metastatic breast cancer from 34 sites between July 2013 and March 2017. Patients were treated with LBP monotherapy or in combination for four to six cycles. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 1179 patients were analyzed; 59 (5.0%) were treated with LBP alone, 134 (11.4%) with LBP plus paclitaxel, 263 (22.3%) with LBP plus docetaxel, 237 (20.1%) with LBP plus gemcitabine, 403 (34.2%) with LBP plus vinorelbine, and 83 (7.0%) with other LBP-based regimens. The overall incidence of adverse events (AEs) was 95.2%, and 57.9% of patients had grade >3 AEs. The most common grade >3 AEs were neutropenia (43.9%), leukopenia (39.4%), anemia (17.8%), and thrombopenia (17.7%). LBP monotherapy showed the lowest incidence of grade >3 AEs (39.0%), followed by LBP plus docetaxel (52.9%), LBP plus paclitaxel (59.0%), LBP plus vinorelbine (62.5%), and LBP plus gemcitabine (62.9%). The ORR and DCR were 36.8 and 77.0%, respectively. The median PFS was 5.5 months (95% confidence interval: 5.2-5.9). Conclusion: LBP-based chemotherapy shows favorable efficacy in patients with advanced breast cancer, with manageable safety profile. Trial registration: This trial was registered with ChiCTR.org.cn, ChiCTR-ONC-13003471.

RESUMEN

BACKGROUND: Drug-eluting beads show good safety and promising efficacy when used as part of a transarterial chemoembolization regimen for primary liver cancer. However, data on the clinical efficacy and safety of pirarubicin-loaded beads combined with lobaplatin are lacking in China. AIM: To evaluate the efficacy and safety of transcatheter arterial chemoembolization using pirarubicin-loaded beads combined with lobaplatin for primary liver cancer. METHODS: Between January 2019 and March 2020, 60 patients with primary liver cancer were selected at Hebei North University Affiliated First Hospital. According to different treatment methods, the participants were categorized into two groups with 30 patients treated with pirarubicin-loaded microspheres combined with lobaplatin included in an observation group and 30 patients treated with pirarubicin emulsion with lipiodol combined with lobaplatin were included in a control group. The progression-free survival, overall survival, clinical response rate, disease control rate, liver and kidney function and adverse reactions were compared between the two groups. RESULTS: The progression-free survival was 14 mo in the observation group, which was significantly higher than 9 mo of the control group (P < 0.05). The 6-mo, 12-mo and 18-mo survival rates were 93.33% (28/30), 66.67% (20/30) and 23.33% (7/30), respectively in the observation group, which were significantly higher than 83.33% (25/30), 50.00% (15/30) and 13.33% (4/30), respectively, of the control group (all P < 0.05). The clinical efficacy rate and disease control rate were 73.33% and 93.33%, respectively, in the observation group, which were significantly higher than those of the control group (53.55% and 80.00%, respectively, all P < 0.05). There was no significant difference in alpha-fetoprotein between the two groups before the treatment (P > 0.05). After the treatment, alpha-fetoprotein was 289.06 ± 76.21 ng/mL in the observation group and 365.01 ± 73.11 ng/mL in the control group, which were low in both groups compared with those before the treatment (all P < 0.05). The incidence of nausea and vomiting was significantly lower in the observation group than in the control group (P < 0.05). There was no significant difference for the adverse reactions of pain and fever between the two groups (P < 0.05). CONCLUSION: The combination of pirarubicin-loaded beads and lobaplatin can improve treatment efficacy resulting in mild liver function damage and postoperative complications in patients with primary liver cancer. It can be used in clinical practice.

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Background: Endostar and platinum were widely used in the treatment of malignant pleural effusion (MPE), but there was no unified conclusion on which scheme is the best. The aim of this study was to systematically evaluate the efficacy and cost-effectiveness of Endostar, cisplatin, lobaplatin, Endostar combined with cisplatin, and Endostar combined with lobaplatin in the treatment of MPE so as to provide a reference for clinical treatment. Methods: A comprehensive literature search was performed of sources on PubMed, Web of Science, and other databases published up to and including November 23, 2021, and screened out randomized controlled trial (RCT) concerning the efficacy of 5 interventions of pleural perfusion for MPE. The Cochrane Collaboration tool was used for assessing the risk of bias, and a network meta-analysis was performed with Addis software based on the Bayesian framework. A decision tree model was used to complete a cost-effectiveness analysis that was based on the direct medical costs and the probabilities were determined from the network meta-analysis. The one-way sensitivity analysis was presented with a tornado chart. In the probabilistic sensitivity analysis, the cost-effectiveness acceptability curve was obtained after Monte Carlo simulation. Results: A total of 55 studies were included, comprising 3,379 total patients, excluding the unclear part, we evaluated as low risk of bias. According to the network meta-analysis, Endostar combined with lobaplatin had the highest effectiveness, followed by Endostar combined with cisplatin, Endostar, cisplatin, and lobaplatin. In the incremental cost-effectiveness ratio (ICER) analysis, lobaplatin and Endostar were excluded as inferior schemes. With cisplatin as the comparison, the ICER of Endostar combined with cisplatin was yuan renminbi ¥22,648.31. With Endostar combined with cisplatin as the comparison, the ICER of Endostar combined with lobaplatin was ¥236,502.67. The results of sensitivity analysis and cost-effectiveness analysis were basically consistent. Conclusions: Endostar combined with lobaplatin had the highest effectiveness, but its ICER was relatively too high to be acceptable. Therefore, cisplatin alone and Endostar combined with cisplatin were more cost-effective, and clinicians can choose the optimal treatment scheme based on the willingness to pay (WTP) of different patients with comprehensive consideration of effectiveness and economy.

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Purpose: We report the 5-year follow-up findings of a randomized, open-label, phase II trial of lobaplatin-based neoadjuvant chemotherapy plus adjuvant therapy for triple-negative breast cancer (TNBC). Patients and methods: This study included patients aged ⩾18 years with untreated, operable stage I-III TNBC and an Eastern Cooperative Oncology Group performance status of 0 or 1. One group of patients (TE group, n = 99) received four cycles of docetaxel (T, 75 mg/m²) plus epirubicin (E, 80 mg/m²) every 3 weeks, and another group (TEL group, n = 101) received the same treatment with the addition of lobaplatin (L, 30 mg/m2). Two cycles of the corresponding treatments were administered after surgery in both groups. The primary endpoints were total pathological complete response (tpCR) rate and overall response rate (ORR), and the secondary endpoints were disease-free survival, overall survival, and long-term safety. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-14005019). Results: The median follow-up was 48.2 months (interquartile range: 31.1-60.0). The tpCR rate was 41.4% and 17.8% in the TEL group and TE group, respectively (p < 0.001). The HR for comparison of DFS between the TEL group and TE group was 0.44 (95% CI: 0.21-0.90, P p = 0.028). The addition of lobaplatin resulted in an HR of 0.44 (95% CI: 0.18-1.02, P = 0.061) for the difference in OS between the two groups. The ORR, which included complete response and partial response, was 92.9% in the TEL group and 74.3% in the TE group (p = 0.001). The TEL group patients were more likely to develop grade III-IV anemia and thrombocytopenia. No lobaplatin-related deaths or increased risk of long-term toxicity was observed. Conclusion: Neoadjuvant lobaplatin therapy can improve the tpCR and ORR rates of TNBC with tolerable side effects and have a tendency to improve the long-term survival.

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BACKGROUND: Synchronous peritoneal metastasis of colorectal cancer usually predicts a bleak prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) have brought a glimmer of hope to the treatment of peritoneal cancer. Few cases treated with lobaplatin have been reported in the literature and the regimen is controversial. In this case, the comprehensive treatment scheme of lobaplatin-based HIPEC plus CRS and rechallenge using cetuximab plus systemic chemotherapy is effective, especially for the patients with left colon cancer (wild-type RAS). CASE PRESENTATION: A 49 year-old man with signet ring cell carcinoma of sigmoid colon with extensive abdominal metastasis (wild-type RAS) was hospitalized with prolonged abdominal pain, distention and abdominal mass. After receiving HIPEC with lobaplatin and XELOX regimen combined with cetuximab for eight cycles, the patient had been treated with the FOLFIRI regimen and cetuximab for 24 cycles, which discontinued due to myelosuppression. Because the disease recurred unfortunately 4 months later, the FOLFIRI + cetuximab regimen was initiated again and stopped after two cycles. Intestinal obstruction occurred 1 month later, so open total colectomy, CRS + HIPEC and ileorectal anastomosis were performed. Capecitabine adjuvant chemotherapy was administered, followed by the maintenance therapy with FOLFIRI + cetuximab regimen. After that, the patient has been in relatively stable condition. By August 2021, the overall survival is more than 45 months, which displays significant curative effect. CONCLUSION: For peritoneal metastasis from left colon cancer, the management with CRS + lobaplatin HIPEC and rechallenge of systemic chemotherapy plus targeted medicine based on gene detection can dramatically improve prognosis and extend the overall survival.

Asunto(s)

Neoplasias del Colon , Neoplasias Colorrectales , Hipertermia Inducida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cetuximab , Neoplasias del Colon/terapia , Neoplasias Colorrectales/terapia , Terapia Combinada , Ciclobutanos , Procedimientos Quirúrgicos de Citorreducción , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Compuestos Organoplatinos , Pronóstico , Tasa de Supervivencia