Two Hematological Markers Predicting the Efficacy and Prognosis of Neoadjuvant Chemotherapy Using Lobaplatin Against Triple-Negative Breast Cancer.

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.

Taxane combined with lobaplatin or anthracycline for neoadjuvant chemotherapy of triple-negative breast cancer: a randomized, controlled, phase II study.

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.

Lobaplatin hyperthermic intraperitoneal chemotherapy plus cytoreduction and rechallenge using cetuximab for wild-type RAS peritoneal metastatic colon cancer: a case report and literature review.

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.

Quantitative phosphoproteomic analysis reveals chemoresistance-related proteins and signaling pathways induced by rhIL-6 in human osteosarcoma cells.

BACKGROUND: IL-6 plays a pivotal role in resistance to chemotherapeutics, including lobaplatin. However, the underlying mechanisms are still unclear. This study was to investigate the changes in phosphoproteins and their related signaling pathways in the process of IL-6-induced chemoresistance to lobaplain in osteosarcoma cells. METHODS: We performed a quantitative phosphoproteomic analysis of the response of SaOS-2 osteosarcoma cells to recombinant human IL-6 (rhIL-6) intervention prior to lobaplatin treatment. The cells were divided into the control group (Con), the lobaplatin group (Lob), and the rhIL-6-and-lobaplatin group (IL-6). Three biological replicates of each group were included. The differentially expressed phosphoproteins were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Netphos 3.1 was used for the prediction of kinases, and STRING was used for the visualization of protein-protein interactions. The conserved motifs surrounding the phosphorylated residues were analyzed using the motif-x algorithm. Western blot analysis was performed to verify the differential expression of p-FLNC, its predicted kinase and the related signaling pathway. The results of the bioinformatic analysis were validated by immunohistochemical staining of clinical specimens. RESULTS: In total, 3373 proteins and 12,183 peptides, including 3232 phosphorylated proteins and 11,358 phosphorylated peptides, were identified and quantified. Twenty-three significantly differentially expressed phosphoproteins were identified in the comparison between the IL-6 and Lob groups, and p-FLNC ranked second among these phosphoproteins. GO and KEGG analyses revealed the pivotal role of mitogen-activated protein kinase signaling in drug resistance induced by rhIL-6. Four motifs, namely, -SPxxK-, -RxxSP-, -SP-, and -SPK-, demonstrated higher expression in the IL-6 group than in the Lob group. The western blot analysis results verified the higher expression of p-FLNC, AKT1, and p-ERK and the lower expression of p-JNK in the IL-6 group than in the Con and Lob groups. The immunohistochemical staining results showed that p-FLNC, AKT1 and p-ERK1/2 were highly expressed in platinum-resistant clinical specimens but weakly expressed in platinum-sensitive specimens, and platinum-resistant osteosarcoma specimens demonstrated weak expression of p-JNK. CONCLUSIONS: This phosphoproteomic study is the first to reveal the signature associated with rhIL-6 intervention before lobaplatin treatment in human osteosarcoma cells. p-FLNC, AKT1, and MAPK signaling contributes to resistance to lobaplatin in osteosarcoma SaOS-2 cells and may represent molecular targets to overcome osteosarcoma chemoresistance.

Comparison of the short-term efficacy and serum markers between lobaplatin/paclitaxel- And carboplatin/paclitaxel-based adjuvant chemotherapy in patient with ovarian cancer.

WHAT IS KNOWN AND OBJECTIVE: To compare short-term therapeutic efficacies and related changes of serum markers from two chemotherapeutic regimes using lobaplatin or carboplatin in combination with paclitaxel in ovarian cancer patients after cytoreductive surgery. METHODS: 120 patients were recruited with pathologically confirmed ovarian cancer. Patients were equally and randomly divided into two groups receiving paclitaxel (PTX) with lobaplatin (LBP) or carboplatin (CBP, as control), respectively, 21 days as a cycle for 6 cycles. Follow-up was performed for 6 months post-treatment. The therapeutic efficacy, serum levels of CA125 (cancer antigen 125/ mucin 16) and HE4 (Human epididymis protein 4) as well as the quality of life were assessment before and after treatment. RESULTS: No significant difference in therapeutic efficacy was observed between the groups (P > .05). The response rates at 1, 3 and 6 months were 76.7%, 66.7% and 46.7% in the LBP group and 73.3%, 63.3% and 36.7% in the CPB group, respectively. At the end of chemotherapy, serum levels of HE4 and CA125 in both groups returned to normal. However, patients in the LBP group had significantly lower HE4 and CA125 levels than those in the CPB group when examined at 3 or 6 months after chemotherapy (P < .05). Moreover, at the end of follow-up, the quality-of-life score (QLQ-C30) of the LBP group was better than that of the CBP group with statistical significance (P < .05). WHAT IS NEW AND CONCLUSION: Both lobaplatin and carboplatin have decent anti-tumour efficacy to be involved in the standard platinum/paclitaxel-based chemotherapy against ovarian cancer. Lobaplatin, on the other hand, has demonstrated higher efficacy to control the progress of the disease yet less toxicity to warrant better patient quality of life.

Uninfluenced alpha-fetoprotein and treatment of liver primary carcinoma by lobaplatin in combination with 5-fluorouracil and doxorubicin via chemoembolization and transarterial chemoembolization.

Alpha-fetoprotein (AFP) is a protein encoded by the AFP gene and normally produced by the fetus. The purpose of this study is to investigate the efficacy of lobaplatin in combination with 5-fluorouracil (5-FU) and doxorubicin on AFP and treatment of primary carcinoma of the liver by transhepatic arterial chemotherapy and embolization (TACE). Patients with primary carcinoma of the liver who took the TACE for treatment were enrolled in this study and divided randomly into the research group and the control group. Patients in the research group adopted the TACE in combination with lobaplatin, while those in the control group took cisplatin instead in combination with TACE. We compared the baseline data, hepatic indicators before treatment and after 1 month of treatment, efficacy and the incidence rates of adverse events after TACE between two groups. Differences in the baseline data, including Child-pugh grade, type of liver cirrhosis, KPS scores and AFP showed no statistical significance (P >0.05). Before the treatment, we identified no significant differences in the comparison of ALT, AST, TBiL and ALB between two groups (P >0.05), while significant differences emerged after treatment (P <0.05). Also, efficacy comparison revealed the significant difference between the two groups (P <0.05). After TACE, patients in the research group reported 1 case of nausea, 1 of vomiting and 1 of necrotic absorption fever, and those in the control group reported 3 cases of nausea, 5 of vomiting and 4 of necrotic absorption fever, with a significant difference in comparison of the incidence rates (P <0.05). TACE is a promising strategy for the treatment of primary carcinoma of the liver, while lobaplatin, as the 3rd generation of anti-tumor platinum-based drugs, is less toxic than cisplatin, but excels in efficacy.

Pharmacokinetics and tissue distribution in rats of a novel anticancer platinum compound LLC-1903.

LLC-1903, a novel anticancer compound, was synthesized by optimizing the structure, which was derived from altering the leaving group of lobaplatin. It has an excellent in vitro anti-cancer activity, high water solubility, high stability in solution and low in vivo toxicity according to our former study.The plasma pharmacokinetics (PK) and tissue distribution of LLC-1903 and lobaplatin in rats were determined after intravenous administration of a single dose (0.06 mmol/kg body weight). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of platinum (Pt) in plasma and tissue samples.Most PK parameters of the Pt in LLC-1903 showed a significant difference from those of lobaplatin. The plasma level of LLC-1903 is only half of that of lobaplatin (p < 0.01) which could be the direct result of faster drug clearance. The tissue distribution showed that both LLC-1903 and lobaplatin were mainly found in the liver and kidney, and less in other organs. At four time points (0.083, 0.5, 1 and 4 h) after administration, the tissue concentrations of LLC-1903 were almost always significantly higher than those of lobaplatin (p < 0.05 or p < 0.01).

[Efficacy of lobaplatin plus S-1 and the predictive value of circulating tumor cell in patients with advanced gastric cancer].

Objective: To investigate the efficacy and safety of lobaplatin (LBP) plus S-1 for advanced gastric cancer (AGC) and determine the potential role of circulating tumor cells (CTC) for predicting the therapeutic response and prognosis. Methods: From January 2014 to February 2015, 64 consecutive patients with AGC received lobaplatin plus S-1 chemotherapy in Liaocheng People's Hospital. The clinical features, clinical response, adverse effects, prognosis and CTC pre- and post-treatment were retrospectively analyzed. The correlation between CTC and patients' disease control rate (DCR), objective response rate (ORR), progression free survival (PFS) as well as overall survival (OS) were investigated. Results: All 64 patients completed 2 cycles of chemotherapy.The number of patients who achieved complete regression, partial regression, stable and progression were 0, 24 (37.5%), 18 (28.1%) and 22 (34.4%), respectively. ORR was 37.5% and DCR was 65.6%. The median PFS was 10.8 months(95%CI 7.1-12.0) and the median OS was 16.1 months(95%CI 12.4-18.8). The ORR and PFS were not significantly different between patients with baseline CTC≥2 and CTC<2 (25.0% vs 53.6%, P=0.150; 6.2 months vs 7.5 months, P=0.780), while the DCR and OS were significantly different (45.9% vs 90.0%, P=0.008; 10.5 months vs 17.2 months, P<0.001). After 2 cycles of chemotherapy, the ORR and DCR in patients with CTC≥2 were 16.7% and 45.9%, respectively, which were significantly lower than those observed in patients with CTC<2 (50.0% and 90.0%, respectively). The former also had shorter median PFS and OS (6.6 months vs 8.9 months, 8.4 months vs 15.0 months, respectively). Patients with persistently CTC<2 or those exhibiting an conversion to CTC<2 following chemotherapy had an improved PFS and OS, while patients with persistently CTC≥2 or those exhibiting an conversion to CTC≥2 following therapy had shorter PFS and OS.The most frequent adverse effects were grade 1 or 2 gastrointestinal discomfort and myelosuppression. No patients discontinued chemotherapy because of adverse events. Conclusions: Lobaplatin plus S-1 had manageable safety profile and promising antitumor activity in patients with AGC. CTC could be used as a biomarker in evaluating therapeutic response and predicting their prognosis.

Safety and efficacy of lobaplatin combined with 5-fluorouracil as first-line induction chemotherapy followed by lobaplatin-radiotherapy in locally advanced nasopharyngeal carcinoma: preliminary results of a prospective phase II trial.

BACKGROUND: Due to improvements in imaging and radiological techniques as well as the use of chemotherapy, distant metastasis has become the predominant mode of treatment failure in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Platinum-based systemic chemotherapy has shown survival benefits and is now the standard strategy for systemic therapy in patients with LA-NPC. Notably, the third-generation platinum reagent lobaplatin has shown anti-tumor effects in several solid tumors with lower incidences of gastrointestinal, hepatic and renal toxicity relative to other platinum drugs. However, the safety and efficacy of lobaplatin as a first-line regimen in patients with LA-NPC are undetermined. METHODS: Patients with stage III-IVa-b NPC received lobaplatin at a dose of 30 mg/m2 on days 1 and 22 combined with a continuous 120-h intravenous injection of 5-fluorouracil at a dose of 4 g/m2 followed by lobaplatin at a dose of 50 mg/m2 on days 43 and 64 concomitant with intensity-modulated radiation therapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.3.0, respectively. Kaplan-Meier analysis was used to calculate survival rates. RESULTS: Fifty-nine patients were enrolled, and 44 patients (74.6%) received allocated cycles of chemotherapy. The objective response rates were 88.1% (95% confidence interval [CI], 0.77 to 0.95) and 100% after induction chemotherapy (ICT) and concurrent chemoradiotherapy (CRT), respectively. With a median follow-up period of 44 months, the 3-year estimated progression-free survival and overall survival were 86.4% (95% CI, 69.8 to 98.8) and 94.9% (95% CI, 89.5 to 100), respectively. The most common grade 3-4 toxicities were neutropenia (8.5%) and thrombocytopenia (40.7%) after ICT and CRT, respectively. CONCLUSION: Lobaplatin combined with 5-fluorouracil followed by lobaplatin-RT treatment showed encouraging anti-tumor effects with tolerable toxicities in patients with LA-NPC. Randomized controlled trials of lobaplatin in patients with LA-NPC are warranted. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trials Registry and approved on March 31st, 2012, number ChiCTR-ONC-12002060 .

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with lobaplatin and docetaxel improves survival for patients with peritoneal carcinomatosis from abdominal and pelvic malignancies.

BACKGROUND: This work was to evaluate the perioperative safety and efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel in patients with peritoneal carcinomatosis (PC) from gastrointestinal and gynecological cancers. METHODS: Patients were treated by CRS + HIPEC with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at 43 ± 0.5 °C for 60 min. Vital signs were recorded for 6 days after CRS + HIPEC procedures. Perioperative serious adverse events (SAE), hematological, hepatic, renal, and electrolytes parameters, the changes in serum tumor markers (TM) before and after operation, patient recovery, and overall survival (OS) were analyzed. RESULTS: One hundred consecutive PC patients underwent 105 CRS + HIPEC procedures and postoperative chemotherapy. The median CRS + HIPEC duration was 463 (range, 245-820) min, and the highest temperature and heart rate during six postoperative days were 38.6 °C (median 37.5 °C) and 124 bpm (median 100 bpm), respectively. The 30-day perioperative SAE occurred in 16 (15.2 %) and mortality occurred in 2 (1.9 %) patients. Most routine blood laboratory tests at 1 week after surgery turned normal. Among 82 cases with increased preoperative TM CEA, CA125, and CA199, 71 cases had TM levels reduced or turned normal. Median time to nasogastric tube removal was 5 (range, 3-23) days, to liquid food intake 6 (range, 4-24) days, and to abdominal suture removal 15 (range, 10-30) days. At the median follow-up of 19.7 (range, 7.5-89.2) months, the median OS was 24.2 (95 % CI, 15.0-33.4) months, and the 1-, 3-, and 5-year OS rates were 77.5, 32.5, and 19.8 %, respectively. Univariate analysis identified five independent prognostic factors on OS: the origin of PC, peritoneal cancer index, completeness of CRS, cycles of adjuvant chemotherapy, and SAE. CONCLUSIONS: CRS + HIPEC with lobaplatin and docetaxel to treat PC is a feasible procedure with acceptable safety and can prolong the survival in selected patients with PC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00454519.

Simultaneous quantitation of two diastereoisomers of lobaplatin in rat plasma by supercritical fluid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study.

Lobaplatin, consisting of two diastereoisomers, is a third-generation platinum antineoplastic agent that has shown encouraging anticancer activity in a variety of tumor types. To investigate any stereospecificity in the pharmacokinetics of lobaplatin, a novel, simple, rapid and sensitive supercritical fluid chromatography with tandem mass spectrometry method was developed for the simultaneous quantitation of lobaplatin diastereoisomers in rat plasma. After a simple protein precipitation with methanol, the analytes and dexpantoprazole (internal standard) were chromatographed on an Acquity UPC(2) system with a Chiralcel OZ-RH column using a mobile phase consisting of carbon dioxide and methanol (65:35, v/v) at 40°C over 6 min. The assay was linear over a concentration range of 25-15,000 ng/mL for both diastereoisomers using 100 µL of rat plasma for sample preparation. The lower limit of quantification was 25 ng/mL for both compounds, which was sufficient to detect the diastereoisomers in the incurred samples within this study. Intra- and inter-day precisions were below 11.8% and the accuracies were below 4.5%. The validated method was successfully applied to a pharmacokinetic study after an intravenous administration of 7.6 mg/kg lobaplatin to rats. There was no apparent stereospecificity in the pharmacokinetics between the two diastereoisomers of lobaplatin.

Comparison of efficacy and toxicity profiles between paclitaxel/lobapoatin- and cisplatin/5-fluorouracil-based concurrent chemoradiotherapy of advanced inoperable oesophageal cancer.

BACKGROUND AND AIM: Current chemoradiotherapy doesn't usually effectively control oesophageal cancer progression. This study assessed the efficacy and toxicity profiles of paclitaxel/lobaplatin (TL)- and cisplatin/5-fluorouracil (PF)-based concurrent chemoradiotherapy (CCRT) in patients with advanced inoperable oesophageal cancer. METHODS: A total of such 68 patients was recruited and randomised to receive TL or PF-based CCRT. Radiotherapy was given at a total dose of 60-70 Gy over 6 weeks. In the TL group of patients, paclitaxel 60 mg/m(2) was administered intravenously on day 1, 8 and 15 and lobaplatin 30 mg/m(2) was administered on day 2 in two cycles at 3-week intervals. In the PF group, cisplatin 75 mg/m(2) was administered intravenously on day 1, and 5-fluorouracil 500 mg/m(2) and leucovorin 200 mg/m(2) were administered intravenously daily for 5 days in two cycles at 3-week intervals. Adverse events, treatment response and follow-up data were collected. RESULTS: The treatment response rates were 73.53% and 50.00% in the TL and PF groups respectively (P = 0.040). The median tumour progression-free survival (PFS) was 13.0 and 6.5 months in the TL and PF groups respectively (P = 0.034). Compared with PF group, the TL group demonstrated decreased grade 3/4 nausea and vomiting (5.88% vs 35.29%, P = 0.003), decreased granulocytopenia (11.76% vs 32.35%, P = 0.041) and platelet count reduction (32.5% vs 8.8%, P = 0.016). CONCLUSIONS: The TL treatment regimen demonstrated higher efficacy with less overall toxicity in patients with advanced inoperable oesophageal cancer compared with the PF regimen. Further study is warranted to validate our current observations.

Intraperitoneal Irrigation Chemotherapy with Lobaplatin in Locally Advanced Gastric Cancer: A Special Type of Abdominal Chemotherapy.

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.

Lobaplatin-based concurrent chemoradiotherapy in elderly nasopharyngeal carcinoma.

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.

A Clinical Study of Intraoperative Perfusion Chemotherapy in Gastric Cancer: A Prospective Cohort Study.

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.

Evaluation of the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer: A study protocol of prospective single-center, randomized controlled and open label clinical trial (RNPLS-01).

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).

EP300 promotes tumor stemness via epigenetic activation of CRISP3 leading to lobaplatin resistance in triple-negative breast cancer.

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.

Lobaplatin-based prophylactic hyperthermic intraperitoneal chemotherapy for T4 gastric cancer patients: A retrospective clinical study.

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.

Single versus multiple hyperthermic intraperitoneal chemotherapy applications for T4 gastric cancer patients: Efficacy and safety profiles.

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.

Efficacy and Safety of Lobaplatin-TACE in the Treatment of Primary Hepatocellular Carcinoma: A Retrospective Study.

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.