A randomized controlled trial of two chemotherapy regimens-paclitaxel liposome combined with platinum and paclitaxel combined with platinum in concurrent chemoradiotherapy for cervical carcinoma

Objective:The aim of the study was to compare the efficacy,side effect and influence on the survival rate of two chemotherapy regimens,paclitaxel liposome combined with platinum and paclitaxel combined with platinum,in concurrent chemoradiotherapy for cervical carcinoma.Methods:The 162 cases with primary cervical carcinoma diagnosed between January 2008 and November 2009 in Jiangxi Maternal and Child Health Hospital(China) were enrolled in this randomized controlled trial.Seventy-one cases were included in paclitaxel group and 91 in paclitaxel liposome group.And the chemotherapy doses were as follows:paclitaxel liposome and paclitaxel 135 mg/m2;cisplatin 80 mg/m2 or carboplatin AUC 4-6;then repeated every 21 days for two or three times.Radical radiotherapy was given to both groups at the same time.Efficacy was evaluated according to the tumor regression six months later and follow-up was done consistently.Results:The overall response rates of paclitaxel group and paclitaxel liposome group were 90.1% and 89 % respectively(P > 0.05).The one year cumulative survival was 91.4% for paclitaxel group and 89.2% for paclitaxel liposome group(P > 0.05).The incidence rates of adverse effects such as rash,gastrointestinal toxicity,bone marrow suppression and muscle/joint pain in paclitaxel liposome group were much lower than those in paclitaxel group(P < 0.05),while there was no difference regarding hair loss,hepatic function damage,peripheral neuritis and other aspects(P > 0.05).Conclusion:Paclitaxel liposome plus platinum is a safe and effective method for staging IIa-IV cervical carcinomas.While the long-term efficacy should be further observed.

17 cases of advanced non-small cell lung cancer treated with paclitaxel liposome plus nedaplatin

Objective： The aim of this study was to evaluate the recent efficacy and adverse reactions of paclitaxel liposome plus nedaplatin in the treatment of advanced non-small cell lung cancer （NSCLC）. Methods： Seventeen cases of NSCLC treated with paclitaxel liposome and nedaplatin for 2 to 6 cycles, by infusing paclitaxel liposome 135 mg/m^2 for 3 h on d 1 and nedaplatin 80 mg/m^2 as infusion on d2. Results： Among 17 patients being evaluated for response to treatment, 1 achieved complete response （CR）, 4 achieved partial response （PR）, 3 achieved stable disease （SD）, 9 achieved progress disease （PD）. The main adverse reaction was haematological toxicities, especially leukopenia and thrombocytopenia. The non-hae- matological toxicities included nausea, vomiting, mild hepatic dysfunction, alopecia and so on. Conclusion： Paclitaxel lipo- some plus nedaplatin was effective and well tolerated for treating patients with advanced NSCLCo

Chidamide Combined with Paclitaxel Liposome for the Treatment of Advanced HER2-negative Breast Cancer in Clinical Study

The purpose of this study was to investigate the efficacy and safety of chidamide combined with paclitaxel liposome in the treatment of advanced HER-2-negative breast cancer.First,41 patients with advanced HER-2-negative breast cancer who had received two chemotherapy regimens from May 2017 to November 2017 were randomly selected to receive chidamide combined with paclitaxel liposome treatment(observation group,n=20)or placebo combined with paclitaxel liposome treatment(control group,n=21).The treatment scheme of the observation group was oral chidamide 30mg twice a week for 2 months.In addition,on day 1,the patients were given paclitaxel liposome orally and intravenously administered with 175 mg/m2 for 1 cycle for 21 days and 3 cycles of chemotherapy.The treatment scheme of the control group was oral placebo 30 mg twice a week for 2 months.In addition,the method of paclitaxel liposome administration was the same as the observation group.The response rate(RR),disease control rate(DCR),and progression-free survival(PFS)were compared between the two groups.The results showed that all the 41 patients could be evaluated.In the observation group,CR5,PR7,SD5 and PD3 were obtained.RR was 60.0%and DCR was 85.0%.In the control group,CR3,PR3,SD5 and PD10 were obtained.RR was 28.6%and DCR was 52.4%.RR and DCR in the observation group were better than those in the control group,and the difference was statistically significant(P<0.05).The median PFS of the observation group was 5.2 months,longer than that of the control group(3.1 months,P<0.05).The main adverse reactions in the two groups were gastrointestinal reactions and bone marrow suppression,with grade 1~2 as the main ones.The incidence of leukopenia,thrombocytopenia and nausea and vomiting in the observation group was higher than that in the control group(P<0.05).Therefore,the chidamide combined with paclitaxel liposome is effective in the treatment of advanced HER-2-negative breast cancer,and the adverse reactions can be tolerated.

Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer:a multicenter,open-label,non-inferiority,randomized controlled trial

Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.

Clinical study of comparing LP and TP regimens in the treatment of advanced non-small cell lung cancer

Objective:The aim of the study was to evaluate the responses and toxicities of liposome encapsulated paclitaxel (LEP) plus cisplatin (DDP) (LP regimen) and paclitaxel (TAX) plus DDP (TP regimen) in the treatment of advanced non-small cell lung cancer (NSCLC). Methods: A total of 89 cases with advanced NSCLC was randomized into two groups: the LP group (57 patients) and the TP group (32 patients). The responses, toxicities and survivals of the two groups were compared. Results: The response rates were 40.00% and 38.71% in the LP and TP groups respectively, but no significant difference was detected between them (P>0.05). The median times to progression (TTP), median remission times, median survival times and 1-year survival rates were 18 weeks, 20 weeks, 35 weeks and 35.09% in the LP group, and 17 weeks, 18 weeks, 31 weeks and 28.15% in the TP group, respectively, and no significant differences were detected between them (P>0.05). The incidence of grades I-II peripheral neuritis in the TP group (37.50%) was significantly higher than that in the LP group (19.29%) (P<0.05). The incidence of grades I-II allergic reaction in the TP group (12.50%) was significantly higher than that in the LP group (5.26%) (P<0.05). And the incidence of grades Ⅲ-IV nausea/vomiting in the TP group (15.63%) was significantly higher than that in the LP group (5.26%) (P<0.01), too. Conclusion: The effect of LP regimen is similar to that of TP regimen, but the incidences of peripheral neuritis, allergic reaction and nausea/vomiting in LP regimen are lower than those in TP regimen. In short, LP regimen may be the first-line chemotherapy regimen of advanced NSCLC.

Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first-line treatment of advanced esophageal squamous cell carcinoma

Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC.Randomized trials to evaluate this new combination strategy are warranted.Trial registration:This trial was registered on July 27,2018,at ClinicalTrials.gov(identifier:NCT03603756).

Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study

Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we conducted a multicenter,randomized,phase 3 study to compare the efficacy and safety of cis-platin plus Lipusu(LP)versus cisplatin plus gemcitabine(GP)as first-line treat-ment in locally advanced or metastatic LSCC.Methods:Patients enrolled were aged between 18 to 75 years,had locally advanced(clinical stage IIIB,ineligible for concurrent chemoradiation or surgery)or metastatic(Stage IV)LSCC,had no previous systemic chemother-apy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors(version 1.1)before administration of the trial drug.The primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),overall survival(OS),and safety profiles.To explore the possible predictive value of plasma cytokines for LP treatment,plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology.The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.Results:The median duration of follow-up was 15.4 months.237 patients in the LP group and 253 patients in the GP group were included in the per protocol set(PPS).In the PPS,the median PFS was 5.2 months versus 5.5 months in the LP and GP group(hazard rtio[HR]:1.03,P=0.742)respectively.The median OS was 14.6 months versus 12.5 months in the LP and GP group(HR:0.83,P=0.215).The ORR(41.8%versus 45.9%,P=0.412)and DCR(90.3%versus 88.1%,P=0.443)were also similar between the LP and GP group.A significantly lower proportion of patients in the LP group experienced adverse events(AEs)leading to treatment interruptions(10.9%versus 26.4%,P<0.001)or treatment termination(14.3%versus 23.1%,P=0.011).The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR,and 15 cytokines were associated with improved PFS,with 14 cytokines,including TNF-a,IFN-y,IL-6,and IL-8,demonstrating an overlapping trend.Conclusion:The LP regimen demonstrated similar PFS,OS,ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles.The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.