Objective:Based on the findings of the KEYNOTE-048 study,pembrolizumab in combination with platinum and fluorouracil is the standard first-line treatment for recurrent or metastatic head and neck squamous cell carcino...Objective:Based on the findings of the KEYNOTE-048 study,pembrolizumab in combination with platinum and fluorouracil is the standard first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma(R/M HNSCC).The efficacy and safety of pembrolizumab combined with nab-paclitaxel and platinum in such patients remain unexplored.Methods:This single-arm phase 2 study enrolled patients with R/M HNSCC who received pembrolizumab(200 mg),nab-paclitaxel(260 mg/m^(2)),and either cisplatin(75 mg/m^(2))or carboplatin[area under the curve(AUC)5]every 21 d for up to six cycles,followed by pembrolizumab maintenance therapy.The primary endpoint was the objective response rate(ORR).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),duration of response(Do R),overall survival(OS),and safety.Exploratory multi-omics analyses were conducted.Results:Between April 23,2021,and August 20,2023,a total of 67 patients with R/M HNSCC were enrolled and received the study treatment.By the data cut-off date of March 2,2024,62(92.5%)patients had received cisplatin,while five(7.5%)patients had received carboplatin.The median follow-up duration was 12.7(range:2.3-34.8)months.The ORR was 62.7%,and the DCR was 88.1%.The median PFS,Do R,and OS were 9.7,13.0,and 18.7 months,respectively.The most common grade 3 adverse events(AEs)were leukopenia(22.4%)and neutropenia(28.4%).Genomic alterations correlated with efficacy outcomes,and dynamic changes in 17 plasma proteins were associated with treatment response.Upregulation of serum interferon(IFN)-γand interleukin(IL)8levels was linked to treatment-related AEs.Conclusions:Pembrolizumab in combination with nab-paclitaxel and platinum demonstrated promising efficacy and a manageable safety profile in patients with R/M HNSCC.Future studies are warranted to confirm these findings.展开更多
Background: The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone(CHOP) is an eicient treatment of non-Hodgkin's lymphoma(NHL). This study aimed to assess the eicacy and toxicity of dose-adju...Background: The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone(CHOP) is an eicient treatment of non-Hodgkin's lymphoma(NHL). This study aimed to assess the eicacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab(R-CHOP) by examining the stem cell mobilization in NHL patients. Factors afecting the collection of CD34+ cells were also explored.Methods: Our retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were inancially eligible received R-CHOP for autologous peripheral blood stem cell(APBSC) mobilization; the remaining 25 patients received CHOP.Results: The median CD34+ cell yield was 7.01 × 106 cells/kg body weight(range 1.49–28.39 × 106 cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of ber of apheresis procedures per patient was 1(range 1–3). The≥2.0 APBS× 106 cells/kg body weight. The median numC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group(P response(CR) rate in = 0.005), whereas the success rate was similar between groups. R-CHOP elevated the completeB cell lymphoma patients as compared with CHOP(P = 0.01). No signiicant diferences in toxicity or engraftment were observed between the two groups.Conclusion: The present study demonstrated that dose-adjusted CHOP chemotherapy efectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma.展开更多
Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Ho...Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.展开更多
Objective： The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor（PEG rhG-CSF） is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy.However, ...Objective： The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor（PEG rhG-CSF） is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy.However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy.Methods：Eligible patients received 3-cycle chemotherapy every 3 weeks.No PEG rhG-CSF was given in the first cycle.Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3.In cycle 2,patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3,and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5,respectively.Escalating doses（30,60,100 and 200μg/kg）of PEG rhG-CSF were investigated.Results：A total of 26 patients were enrolled and received chemotherapy,in which 24 and 18 patients entered cycle 2 and cycle 3 treatment,respectively.In cycle 2,the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30,60,100 and 200 μg/kg was 66.67%,33.33%,22.22% and 0,respectively,with a median duration less than 1（0–2）d.No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts.Conclusions：The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported,as well as the safety.Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above.The single dose of 60 μg/kg,100 μg/kg and double half dose of 30 μg/kg were recommended to the phase Ⅱ study,hoping to find a preferable method for neutropenia treatment.展开更多
Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stroma...Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers(carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular basis of ovarian carcinomas represents the first step in the development of targeted therapies in the near future.展开更多
Background:Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs).It causes thrombocytopenia and delays leukaphe...Background:Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs).It causes thrombocytopenia and delays leukapheresis.This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma.Methods:In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm).The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored.Results:Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy (P=0.878) and similar amount of platelet transfusion (median 0 vs.1 unit,P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 ×10^(9)/L (range 18-219) among patients who received rhTPO and 73 ×10^(9)/L (range 42-197) among those who received GCSF alone (P=0.982). After the use of rhTPO, the incidence of platelet count <75 ×10^(9)/L on the day of leukapheresis did not decrease significantly (30.0% vs. 50.0%,P=0.297).Platelet recovery after PBPC transfusion was more rapid in the rhTPO plus GCSF arm (median 8.0 days [95% confidence interval 2.9-13.1] to platelets ≥50 ×10^(9)/L vs. 11.0 days [95% confidence interval 8.6-13.4],P=0.011).The estimated total cost of the mobilization and reconstitution phases per patient was similar between the two treatmtent groups (P=0.362 andP=0.067,respectively).Conclusions:Our findings indicate that there was no significant clinical benefit of rhTPO use in facilitating mobilization of progenitor cells,but it may promote platelet recovery in the reconstitution phase after high-dose therapy.Trial registration:This trial has been registered in Clinicaltrials.gov as NCT03014102.展开更多
基金supported by the China National Major Project for New Drug Innovation(No.2017ZX09304015)the Beijing Hope Run Special Fund of the Cancer Foundation of China(No.LC2022A30)the Beijing Vlove Charity Foundation(No.JYKY2024-0200616033)。
文摘Objective:Based on the findings of the KEYNOTE-048 study,pembrolizumab in combination with platinum and fluorouracil is the standard first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma(R/M HNSCC).The efficacy and safety of pembrolizumab combined with nab-paclitaxel and platinum in such patients remain unexplored.Methods:This single-arm phase 2 study enrolled patients with R/M HNSCC who received pembrolizumab(200 mg),nab-paclitaxel(260 mg/m^(2)),and either cisplatin(75 mg/m^(2))or carboplatin[area under the curve(AUC)5]every 21 d for up to six cycles,followed by pembrolizumab maintenance therapy.The primary endpoint was the objective response rate(ORR).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),duration of response(Do R),overall survival(OS),and safety.Exploratory multi-omics analyses were conducted.Results:Between April 23,2021,and August 20,2023,a total of 67 patients with R/M HNSCC were enrolled and received the study treatment.By the data cut-off date of March 2,2024,62(92.5%)patients had received cisplatin,while five(7.5%)patients had received carboplatin.The median follow-up duration was 12.7(range:2.3-34.8)months.The ORR was 62.7%,and the DCR was 88.1%.The median PFS,Do R,and OS were 9.7,13.0,and 18.7 months,respectively.The most common grade 3 adverse events(AEs)were leukopenia(22.4%)and neutropenia(28.4%).Genomic alterations correlated with efficacy outcomes,and dynamic changes in 17 plasma proteins were associated with treatment response.Upregulation of serum interferon(IFN)-γand interleukin(IL)8levels was linked to treatment-related AEs.Conclusions:Pembrolizumab in combination with nab-paclitaxel and platinum demonstrated promising efficacy and a manageable safety profile in patients with R/M HNSCC.Future studies are warranted to confirm these findings.
基金supported in part by Grants from National Science-Technology Support Plan Projects of China (2014BAI09B12)National Major Project for New Drug Innovation of China (2008ZX09312 and 2012ZX09303012)the Ministry of Education Doctor Foundation of China (20010023018, 20050023045, and 200800230019)
文摘Background: The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone(CHOP) is an eicient treatment of non-Hodgkin's lymphoma(NHL). This study aimed to assess the eicacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab(R-CHOP) by examining the stem cell mobilization in NHL patients. Factors afecting the collection of CD34+ cells were also explored.Methods: Our retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were inancially eligible received R-CHOP for autologous peripheral blood stem cell(APBSC) mobilization; the remaining 25 patients received CHOP.Results: The median CD34+ cell yield was 7.01 × 106 cells/kg body weight(range 1.49–28.39 × 106 cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of ber of apheresis procedures per patient was 1(range 1–3). The≥2.0 APBS× 106 cells/kg body weight. The median numC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group(P response(CR) rate in = 0.005), whereas the success rate was similar between groups. R-CHOP elevated the completeB cell lymphoma patients as compared with CHOP(P = 0.01). No signiicant diferences in toxicity or engraftment were observed between the two groups.Conclusion: The present study demonstrated that dose-adjusted CHOP chemotherapy efectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma.
基金supported in part by Chinese National Major Project for New Drug Innovation (2008ZX09312-020,2009ZX09503-014,2012ZX09303012 and 2013ZX09402301)National Key Technology Support Program (2014BAI09B12)+1 种基金Beijing Municipal Science and Technology Commission Major Project for New Drug Innovation (Z111102071011001)Beijing Municipal Science and Technology Commission Project for Beijing Key Laboratory (Z121102009212055)
文摘Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.
基金supported by Hangzhou Jiuyuan Gene Engineering Co., Ltdpartly funded by the Chinese National Science and Technology Major Project on Key New Drug Creation (2012ZX09303-012)Beijing Municipal Science & Technology Commission Major Project for New Drug Innovation (Z111102071011001), China
文摘Objective： The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor（PEG rhG-CSF） is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy.However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy.Methods：Eligible patients received 3-cycle chemotherapy every 3 weeks.No PEG rhG-CSF was given in the first cycle.Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3.In cycle 2,patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3,and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5,respectively.Escalating doses（30,60,100 and 200μg/kg）of PEG rhG-CSF were investigated.Results：A total of 26 patients were enrolled and received chemotherapy,in which 24 and 18 patients entered cycle 2 and cycle 3 treatment,respectively.In cycle 2,the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30,60,100 and 200 μg/kg was 66.67%,33.33%,22.22% and 0,respectively,with a median duration less than 1（0–2）d.No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts.Conclusions：The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported,as well as the safety.Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above.The single dose of 60 μg/kg,100 μg/kg and double half dose of 30 μg/kg were recommended to the phase Ⅱ study,hoping to find a preferable method for neutropenia treatment.
文摘Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers(carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular basis of ovarian carcinomas represents the first step in the development of targeted therapies in the near future.
基金This work was supported by Beijing Hope Run Special Fund of Cancer Foundation of China(LC2016B03)。
文摘Background:Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs).It causes thrombocytopenia and delays leukapheresis.This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma.Methods:In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm).The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored.Results:Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy (P=0.878) and similar amount of platelet transfusion (median 0 vs.1 unit,P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 ×10^(9)/L (range 18-219) among patients who received rhTPO and 73 ×10^(9)/L (range 42-197) among those who received GCSF alone (P=0.982). After the use of rhTPO, the incidence of platelet count <75 ×10^(9)/L on the day of leukapheresis did not decrease significantly (30.0% vs. 50.0%,P=0.297).Platelet recovery after PBPC transfusion was more rapid in the rhTPO plus GCSF arm (median 8.0 days [95% confidence interval 2.9-13.1] to platelets ≥50 ×10^(9)/L vs. 11.0 days [95% confidence interval 8.6-13.4],P=0.011).The estimated total cost of the mobilization and reconstitution phases per patient was similar between the two treatmtent groups (P=0.362 andP=0.067,respectively).Conclusions:Our findings indicate that there was no significant clinical benefit of rhTPO use in facilitating mobilization of progenitor cells,but it may promote platelet recovery in the reconstitution phase after high-dose therapy.Trial registration:This trial has been registered in Clinicaltrials.gov as NCT03014102.
