Lobaplatin Group Research Articles

The inhibitory effects of lobaplatin, or in combination with gemcitabine on triple-negative breast cancer cells in vitro and in vivo

Abstract Objectives To study the therapeutic effects of lobaplatin in combination with conventional chemotherapy drugs on triple-negative breast cancer (TNBC) cells. Methods We used the CCK-8 assay, flow cytometry, western blotting, and immunofluorescence staining methods to detect the effects of lobaplatin or in combination with gemcitabine on the survival, apoptosis, and cell cycle progression of TNBC cells. A cell-derived xenograft mouse model was used to verify the antitumor effects of lobaplatin alone or in combination with gemcitabine. Results Lobaplatin significantly inhibited MDA-MB-468 cell growth in vitro, either alone or in combination with gemcitabine. Lobaplatin arrested the cell cycle at the S phase, induced nuclear cell damage, and promoted apoptosis. Also, the percentage of apoptotic cells was greatly increased when lobaplatin was combined with gemcitabine. Cleaved Caspase-3 and Poly (ADP-Ribose) Polymerase-1 (PARP-1) fragments indicated that lobaplatin promoted apoptosis through the classical pathway. Lobaplatin effectively inhibited the growth of tumors in vivo. Compared with the vehicle group (567.6 ± 126.2 mm3), the tumor volume of the lobaplatin group (302.7 ± 131.6 mm3) was significantly reduced (p<0.01). The combination of lobaplatin and gemcitabine (207.7 ± 83.94 mm3) was a little better than lobaplatin alone in the inhibition of the transplanted tumor (p>0.05). Conclusions Lobaplatin alone or in combination with gemcitabine had significant inhibitory effects on MDA-MB-468 cells in vitro. Lobaplatin also significantly inhibited the growth of nude mice xenografts. The synergistic effect between lobaplatin and gemcitabine in vivo was minimal, perhaps due to the low dose of gemcitabine used.

Efficacy and toxicity of three concurrent chemoradiotherapy regimens in treating nasopharyngeal carcinoma: Comparison among cisplatin, nedaplatin, and lobaplatin.

Few studies directly compare efficacy and toxicity among lobaplatin, nedaplatin and cisplatin concurrently with intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). Totally 141 treatment-naïve NPC without distant metastasis receiving IMRT concurrent with cisplatin or nedaplatin or lobaplatin were retrospectively enrolled. Their response rate, toxicity and long-term survival were compared. Complete response (CR) rates of concurrent lobaplatin (CR-nasopharynx [CR-nx], 82.7%; CR-cervical lymph node [CR-nd], 94.2%) were lower than those of cisplatin (CR-nx, 89.3%; CR-nd, 98.2%) and nedaplatin (CR-nx, 93.9%; CR-nd, 97.0%), but statistical significance wasn't detected. Estimated five-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) weren't statistically significant between three groups. Multivariable analysis by COX proportional hazards model showed concurrent chemotherapy regimen wasn't an independent prognostic factor. Gastrointestinal toxicity was prevalent in platinum-based concurrent chemotherapy; cisplatin group suffered heavier (≥grade 2) than other two groups. More nephrotoxicity happened in cisplatin group (17.9%) than nedaplatin (9.1%) and lobaplatin (2.0%) groups. Incidence of dermatitis of ≥grade 2 was higher in cisplatin group (60.7%) than nedaplatin (27.3%) and lobaplatin (9.6%) groups. More patients in lobaplatin and nedaplatin groups suffered from any grade thrombocytopenia (P < .001), but incidence of severe thrombocytopenia (≥grade 3) was similar. Economic cost was significant less in lobaplatin group. Cisplatin, nedaplatin and lobaplatin are equally effective when used concurrently with IMRT in NPC. Lobaplatin and nedaplatin have potential to be alternatives to cisplatin in terms of less severe acute side-effects and economic cost.

Chemotherapy-Induced Myelosuppression in Esophageal Cancer Patients: Risks and Suggestions for Its Management.

The influential factors of chemotherapy-induced myelosuppression in esophageal cancer in central China are unclear. This study aimed to investigate the effect of commonly used chemotherapy regimens on the incidence of myelosuppression in clinical treatment of esophageal cancer. In this retrospective study, 624 patients with esophageal cancer who received six different chemotherapy regimens between 2013 and 2020 at our institute were included. Chemotherapy consisted of lobaplatin, 5-fluorouracil (5-F), lobaplatin and 5-F, nedaplatin, nedaplatin and paclitaxel (PTX), cisplatin and PTX. Multivariable logistic regression analysis was used to explore the risk of myelosuppression among the six different chemotherapy regimens. Compared with lobaplatin group, the incidence of myelosuppression in patients treated with chemotherapy regimens of lobaplatin and 5-F, nedaplatin, nedaplatin and PTX and cisplatin and PTX were significantly ameliorated. The dose of lobaplatin was significantly reduced (P=0.007) when lobaplatin was combined with 5-F, and the combination could significantly reduce the risk of myelosuppression (P=0.022). Furthermore, chemotherapeutic regimens, the dose of platinum, hemoglobin and uric acid levels, age, sex, total bilirubin and immune-enhancing drugs were found to be strong predictors of developing myelosuppression. Targeted preventive interventions that enhance immune function, reduce uric acid levels and choose combined medication during chemotherapy should be implemented for high-risk patients to reduce the occurrence of myelosuppression. In addition, the dose of lobaplatin should be adjusted when combined with other chemotherapy drugs to reduce the incidence of myelosuppression.

Elemene-containing hyperthermic intraperitoneal chemotherapy combined with chemotherapy for elderly patients with peritoneal metastatic advanced gastric cancer.

BACKGROUNDAlmost all elderly patients with peritoneal metastatic gastric cancer (PGC) are unlikely to tolerate cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and adjuvant chemotherapy. However, determining how to optimize the treatment strategy for such patients has always been a clinical problem. Both HIPEC and palliative adjuvant chemotherapy can benefit patients with PGC. Therefore, optimizing HIPEC and chemotherapy regimens has potential clinical value in reducing side effects, and improving treatment tolerance and clinical effectiveness.AIMTo explore the effect of HIPEC containing elemene, which is an anti-cancer component extracted in traditional Chinese herbal medicine, combined with reduced capecitabine and oxaliplatin (CapeOx) chemotherapy regimens, in elderly patients with PGC.METHODSIn the present study, 39 of 52 elderly PGC patients were included and assigned to different HIPEC treatment groups [lobaplatin group (group L) and mixed group (group M)] for analysis. Lobaplatin was used for all three HIPECs in group L. In group M, lobaplatin was used in the middle of the three HIPECs, and elemene was used for the first and third HIPEC. After HIPEC, patients received CapeOx chemotherapy. The incidence of complications (abdominal infection, lung infection, and urinary tract infection), myelosuppression, immune function (CD4/CD8 ratio), average length of hospital stay, and prognosis were compared between these two groups.RESULTSThere was no significant difference in the incidence of complications between the two groups during hospitalization (P > 0.05). Compared to patients in group M, patients in group L exhibited severe myelosuppression (P = 0.027) and increased length of hospital stay (P = 0.045). However, no overall survival benefit was observed in group M. Furthermore, the immune function of patients in group M was less affected (P < 0.001), when compared to that of patients in group L. The multivariate analysis suggested that the cycles of chemotherapy after perfusion significantly affected the prognosis of patients in both groups.CONCLUSIONCompared to the lobaplatin-based HIPEC regimen, the administration of elemene reduced the myelosuppression incidence in elderly PGC patients. The present study sheds light on the implementation of this therapeutic strategy for this set of patients.

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

BackgroundIL-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.MethodsWe 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.ResultsIn 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.ConclusionsThis 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.

Hematological Toxicities of Concurrent Chemoradiotherapies in Head and Neck Cancers: Comparison Among Cisplatin, Nedaplatin, Lobaplatin, and Nimotuzumab.

BackgroundCisplatin-based concurrent chemoradiotherapy is standard of care for locally advanced head and neck cancers (LAHNC). Nedaplatin, lobaplatin and nimotuzumab have shown anti-cancer effect with less gastrointestinal toxicity and nephrotoxicity. However, the profile of hematological toxicities of these agents in combination with radiotherapy has not been fully illustrated.MethodsWe retrospectively collected the clinical data of consecutive LAHNC patients treated by cisplatin-, nedaplatin-, lobaplatin-, and nimotuzumab-based concurrent chemoradiotherapy. Routine blood cell counts were obtained every 4 to 7 days. Hematological toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.ResultsA total of 181 eligible LAHNC patients were assigned to nimotuzumab group (n = 34), cisplatin group (n = 52), nedaplatin group (n = 62) or lobaplatin group (n = 33). Among the four groups, nimotuzumab group displayed lightest hematological toxicities, followed by cisplatin group, nedaplatin group, and lobaplatin group. Lobaplatin was more likely to produce grade 3/4 leukopenia compared with cisplatin (48.5% vs 25.0%). Compared with cisplatin, nedaplatin and lobaplatin were more likely to cause grade 3/4 thrombocytopenia (nedaplatin 19.4% vs cisplatin 3.8%; lobaplatin 30.3% vs cisplatin 3.8%). Similarly, nimotuzumab group showed highest nadir levels among the four groups, followed by cisplatin, nedaplatin, and lobaplatin group. Moreover, concurrent platinum treatment and induction chemotherapy were risk factors of developing grade 3/4 hematological toxicities.ConclusionNimotuzumab-based concurrent chemoradiotherapy in head and neck cancers produced the lightest hematological toxicities, followed by cisplatin, nedaplatin, and lobaplatin. Patients should be given specific attention during concurrent chemoradiotherapy, particularly in the presence of previous induction chemotherapy.

Lobaplatin-Based Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Metastasis from Appendiceal and Colorectal Cancer: Safety and Efficacy Profiles.

ObjectiveThis study aimed to evaluate the safety and efficacy of lobaplatin in hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastasis (PM) arising from colorectal or appendiceal cancer.Materials and MethodsPatients with synchronous or metachronous PM who underwent cytoreductive surgery (CRS) with HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. All enrolled patients were grouped into either lobaplatin or nonlobaplatin groups depending on the different chemotherapeutic agents used during HIPEC. Clinical characteristics, pathological features, perioperative parameters, and prognostic data were collected and analyzed.ResultsA total of 100 patients were enrolled, with 48 patients in the lobaplatin group and 52 in the nonlobaplatin group. The two groups were well balanced in terms of clinicopathological characteristics. The two groups had comparable perioperative outcomes. However, more patients in the lobaplatin group than in the nonlobaplatin group developed abnormal platelet levels on postoperative day (POD)3 and abnormal ALT levels on POD5. Moreover, the average platelet count in the lobaplatin group was significantly lower than that in the nonlobaplatin group on POD5. There were no significant differences in the 3-year overall survival (OS) rates (48.4% vs 35.1%, P=0.298) and the 3-year progression-free survival (PFS) rates (34.9% vs 21.0%, P=0.470) of the two groups.ConclusionLobaplatin-based HIPEC is safe and feasible for the treatment of patients with PM arising from colorectal or appendiceal cancer with comparable low mortality and acceptable morbidity.

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

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. 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, 21days as a cycle for 6 cycles. Follow-up was performed for 6months 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. No significant difference in therapeutic efficacy was observed between the groups (P>.05). The response rates at 1, 3 and 6months 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 6months 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). 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.

Comparison of the Short term Efficacy and Serum Markers between Lobaplatin/Paclitaxel- and Carboplatin/Paclitaxel-based Adjuvant Chemotherapy in Patients with Ovarian Cancer

To compare short-term therapeutic efficacies and related changes of serum markers from 2 chemotherapeutic regimes using lobaplatin or carboplatin in combination with paclitaxel in ovarian cancer patients after cytoreductive surgery. 60 patients were recruited with confirmed ovarian cancer. Patients were equally and randomly divided into 2 groups receiving paclitaxel with lobaplatin or carboplatin, respectively. Follow-up was made 6 months post-treatment. The therapeutic efficacy, serum levels of cancer antigen 125/mucin 16 and human epididymis protein 4 as well as the quality-of-life were assessed before and after treatment. No significant difference in therapeutic efficacy was observed between the groups. The response rates at 1, 3 and 6 months were 76.7 % (23/30), 66.7 % (20/30) and 46.7 % (14/30) in the lobaplatin group and 73.3 % (22/30), 63.3 % (19/30), 36.7 % (11/30) in the carboplatin group, respectively. At the end of the chemotherapy, serum levels of human epididymis protein 4 and cancer antigen 125 in both groups returned to normal. However, patients in the lobaplatin group had significantly higher Human epididymis protein 4 and cancer antigen 125 levels than those in the carboplatin group when examined at 3 or 6 month after chemotherapy (p<0.05). Moreover, at the end of follow-up, the quality-of-life score-C30 of the lobaplatin group was better than that of the carboplatin group with statistical significance (p<0.05). Both lobaplatin and carboplatin exert sufficient antitumor efficacy to be included 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.

Paclitaxel increases the sensitivity of lung cancer cells to lobaplatin via PI3K/Akt pathway.

The effect of paclitaxel combined with lobaplatin on the sensitivity of lung cancer cell line NCI-H446 through influencing the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was investigated. The sensitivity of lobaplatin to NCI-H446 and the effect of paclitaxel and PI3K inhibitor LY294002 combined with lobaplatin on the sensitivity to NCI-H446 were detected via methyl thiazolyltetrazolium (MTT) assay. The effect of paclitaxel combined with lobaplatin on cell apoptosis was detected using flow cytometry, the effect of paclitaxel combined with lobaplatin on the cell migration was detected via cell wound scratch assay, and the effect of paclitaxel combined with lobaplatin on the cell invasion was detected via Transwell assay. Finally, the effect of paclitaxel on PI3K/Akt pathway was detected via western blotting. MTT assay showed that 30 µg/ml lobaplatin could significantly inhibit the growth of NCI-H446 (p<0.01). Lobaplatin group (group L), 2 µg/ml paclitaxel combined with lobaplatin group (group LP) and lobaplatin combined with 10 µmol/ml LY294002 group (group LL) were set up. The cell survival rates in group LP and group LL were significantly lower than that in group L (p<0.01), and the cell survival rate in group LP was similar to that in group LL (p>0.05). Flow cytometry revealed that the cell apoptotic levels in group LP and group LL were obviously higher than that in group L (p<0.01), and there was no statistically significant difference in the cell apoptotic level between group LP and group LL (p>0.05). Cell wound scratch assay showed that the cell migration capacity in group LP was significantly lower than those in group L and group LL (p<0.01, p<0.05), and the cell migration capacity in group LL was lower than that in group L (p<0.05). Besides, Transwell assay revealed that the cell invasion capacity in group LP was obviously lower than those in group L and group LL (p<0.01, p<0.05), and the cell invasion capacity in group LL was lower than that in group L (p<0.01). Finally, western blotting showed that the levels of PI3K, phosphorylated-Akt (p-Akt) and phosphorylated-glycogen synthase kinase 3β (p-GSK3β) in group LP and group LL were significantly lower than those in group L, and the differences were statistically significant (p<0.01). Paclitaxel can significantly increase the sensitivity of lobaplatin to lung cancer cell line NCI-H446. Moreover, paclitaxel can enhance the effect of lobaplatin on lung cancer cells and reduce the drug resistance through inhibiting PI3K/Akt pathway.

Inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung cancer xenografts in nude mice

To evaluate the inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung adenocarcinoma xenografts in nude mice, and to explore its possible mechanisms. Human lung cancer A549 cells were injected into Bal B/c nude mice subcutaneously. Twenty-eight healthy male nude mice were randomly divided into 4 groups: the control group, imrecoxib group, lobaplatin group and imrecoxib combined with lobaplatin group. Each group was treated with appropriate drugs and the tumor size was measured every five days. The expression of ezrin and E-cadherin protein was detected by immunohistochemistry and flow cytometry. Ezrin and E-cadherin mRNA were detected by real-time PCR. The tumor inhibition rates of imrecoxib group, lobaplatin group and combination group were 36.7%, 54.6% and 69.2%, respectively. The tumor volumes of imrecoxib group [(905.33±113.31) mm(3)] and combination group [(507.74±77.50) mm(3)] were significantly lower than that of the control group (1355.33±189.04) mm(3) (P<0.05), and the tumor weights were significantly reduced [(1.13±0.14) g, (0.63±0.10) g respectively] vs. (1.69±0.24) g (P<0.05). The expressions of ezrin protein and mRNA in the imrecoxib group and combined treatment group were significantly lower than that of the control group (136.53±35.52, 74.72±19.48 vs. 175.62±21.16 for protein expression level; 0.54±0.03, 0.36±0.03 vs. 1.02±0.02 for mRNA expression level, respectively, P<0.05 for both), while the expression of E-cadherin protein and mRNA in the imrecoxib group and combined treatment group was significantly higher than that of the control group (253.78±38.87, 308.94±24.67 vs. 213.66±30.31 for protein expression level; 2.19±0.02, 3.02±0.02 vs. 1.05±0.03 for mRNA expression level, respectively, P<0.05 for both). There was a significant negative correlation between ezrin protein and E-cadherin protein (r=-0.737, P<0.01), as well as between ezrin mRNA and E-cadherin mRNA (r=-0.977, P<0.01). Administration of imrecoxib combined with lobaphatin has inhibitory effects on the growth of non-small cell lung cancer xenografts and lymph node metastasis via down-regulated ezrin and upregulated E-cadherin. Imrecoxib and lobaplatin have a synergistic antitumor effect.

Inhibitory effects of lobaplatin on human ovarian cancer and its regulation of apoptosis-related genes in nude mice

Objective To explore the inhibitory effects of lobaplatin and cisplatin and their regulation of apoptosis-related genes in ovarian cancer cells in nude mice. Methods SKOV3 cells were implanted into nude mice.In monotherapy treatment study, the nude mice bearing human SKOV3 cells were randomly divided into control, lobaplatin, and cisplatin groups, with 7 mice in each group. The mice in each group were received corresponding treatment. The volume of tumor and the weight of nude mice were measured three times per week, respectively. Tumor inhibitory rate was calculated. The protein expressions of bax and bcl-2 were detected by flow cytometry. Results The growth inhibitory rate was 47.2% in lobaplatin group and 42.8% in cisplatin group, without significant difference between two groups (P>0.05). The expression of bcl-2 was decreased but the bax was increased in lobaplatin and ciaplatin groups compared to the control group. Conclusions Lobaplatin can significantly inhibit the growth of ovarian cancer cells, induce apoptosis by down-regulation of bcl-2 and up-regulation of bax. Key words: Organoplatinum compounds/pharmacology; Disease models, animal; Ovarian neoplasms/drug therapy; Mice, nude; Neoplasm transplantation; Genes, bcl-2; Gene expression; Apoptosis

A phase I clinical trial of dose escalation of lobaplatin in combination with fixed-dose docetaxel for the treatment of human solid tumours that had progressed following chemotherapy.

In this study, the maximum tolerated dose (MTD) of lobaplatin (LBP) when it was combined with docetaxel (TXT) for the treatment of solid tumours that had progressed following chemotherapy was determined, and toxicities to this regimen were evaluated. A modified Fibonacci method was used for the dose escalation of LBP. The patients received TXT (at a fixed dose of 60 mg/m2) on day one (d1) and LBP (at an initial tested dose of 30 mg/m2) on day two (d2) of a treatment cycle that was repeated every 21 days. Each dose group consisted of at least three cases. In the absence of dose-limiting toxicity (DLT), we proceeded to the next dose group, with a dose increment of 5 mg/m2 between groups, until DLT occurred. The dose immediately below the dose that produced DLT was regarded as the MTD. The 17 patients examined in this study completed a total of 58 cycles of chemotherapy, and a total of three dose-escalation groups (30 mg/m2 LBP, 35 mg/m2 LBP, and 40 mg/m2 LBP) were established. The main adverse event that was observed was myelosuppression. DLT occurred in four patients, including three patients in the 40 mg/m2 LBP group and one patient in the 35 mg/m2 LBP group. In total, three out of the four patients in the 40 mg/m2 LBP group exhibited DLT. We determined that the treatment administered to the 35 mg/m2 LBP group represented the MTD. Thus, our phase I trial revealed that the MTD for the tested LBP combination regimen was 35 mg/m2 LBP and 60 mg/m2 TXT. This regimen resulted in mild adverse reactions and favourable patient tolerance. Therefore, we recommend the use of these dosages in phase II clinical trials.