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Objective:To compare the efficacy and safety of pegylated liposomal Doxorubicin(PLD)and Epirubicin(EPI)as first-line chemotherapy for diffuse large B-cell lymphoma(DLBCL).Methods:Clinical data of DLBCL patients treated at Zhejiang Cancer Hospital from March 2013 to April 2018 were retrospectively collected.A total of 411 patients who had received first-line chemotherapy were included.Based on age, sex, Ann Arbor staging and other parameters and using the PSM method for 1∶1 matching, 151 patients were assigned into each of the PLD group and the EPI group.Efficacy and adverse events were compared between the PLD group and the EPI group.All patients were followed up for 3 years after treatment to monitor survival.Results:The complete response(CR)rate in the PLD group was 81.5%, and the CR rate in the EPI group was 72.2%.The objective response rate(ORR)of the PLD group was 98%, and the ORR of the EPI group was 96.7%.There was no significant difference in CR rate( χ2=0.478, P=0.489)or ORR between the two groups( χ2=0.007, P=0.934). In the PLD group, myelosuppression occurred in 25 cases(16.6%)and cardiotoxicity-related events in 21 cases(13.9%); in the EPI group, there were 24 cases(15.9%)of myelosuppression and the same number of cases of cardiotoxicity-related events, and there were no significant differences in myelosuppression( χ2=0.018, P=0.895)or cardiotoxicity( χ2=0.174, P=0.677)between the two groups.During the 3-year follow-up, the progression free survival(PFS)rates of the PLD group and the EPI group were 79.1% and 69.6%, respectively, with a statistically significant difference between the two groups( χ2=3.930, P=0.047). Both the PLD group and the EPI group had a 3-year OS rate of 85.2%, with no statistically significant difference between the two groups( χ2=0.402, P=0.538). Conclusions:The 3-year progression-free survival of DLBCL patients with PLD as first-line chemotherapy is significantly better than with EPI, and the 3-year overall survival, short-term efficacy and myelosuppression are comparable to those with EPI.
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As a new type of anthracyclines, pegylated liposomal doxorubicin (PLD) is widely used in the treatment of a variety of malignant tumors, including soft tissue sarcoma, ovarian cancer, breast cancer, multiple myeloma, and so on. Compared with traditional anthracyclines, PLD can significantly decrease the incidences of adverse events such as cardiac toxicity and alopecia. However, the use of PLD will be accompanied with toxic side effects such as hand-foot syndrome, oral mucositis, and infusion reaction. This consensus will mainly focus on the mechanism, prevention and treatment of adverse events of PLD, in order to improve the therapeutic efficacy of PLD and life quality of patients.
Subject(s)
Female , Humans , Antibiotics, Antineoplastic , Therapeutic Uses , Consensus , Doxorubicin , Therapeutic Uses , Drug-Related Side Effects and Adverse Reactions , Hand-Foot Syndrome , Neoplasms , Drug Therapy , Polyethylene Glycols , Therapeutic Uses , Practice Guidelines as Topic , StomatitisABSTRACT
OBJECTIVE: To evaluate the efficacy and safety profile of first-line R-CDOP(rituximab, cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone) like regimen in diffuse large B-cell lymphoma (DLBCL) with cardiovascular diseases or risk factors. METHODS: DLBCL Patients who were diagnosed with at least one cardiovascular disease/risk factor and received first-line R-CDOPlike chemotherapy in our institute between January 2010 and November 2016 were collected. Cardiovascular diseases/risk factors were referred as:coronary heart disease, hypertension, age ≥60, hyperlipidemia, diabetes mellitus, obesity, history of smoking, and hypothyroidism/hyperthyroidism. Chemotherapy in our institute were retrospectively reviewed. RESULTS: A total of 94 DLBCL patients were recruited. All enrolled patients had history of a cardiovascular disease or presented a high-risk group of developing cardiovascular diseases:coronary heart disease 10 cases, hypertension 33 cases, hyperlipidemia 44 cases, diabetes mellitus 23 cases, obesity 15 cases, history of smoking 25 cases, hypothyroidism/hyperthyroidism 3 cases. A total of 74 patients had more than one cardiovascular disease or risk factors. A total of 34 patients were germinal center B-cell subtype(GCB) and 60 were non-germinal center B-cell subtype(non-GCB). First-line R-CDOP like chemotherapy was given at a median cycle of 4.5 (range, 2-8). Overall response rate(ORR) and complete response rate (CRR) were 92.6%(87/94) and 70.2%(66/94) for the whole group. 5-Year progression-free survival (PFS) and overall survival(OS) rates were 71.3% and 76.9% for overall. For GCB subtype and non-GCB subtype, 5-year PFS rates were 84.6% and 63.9% respectively(P<0.05), and 5-year OS rates were 80.6% and 74.6%, respectively(P=0.407). Grade III/ neutropenia and thrombocytopenia were documented in 53.2%(50/94) and 3.2% (3/94) of patients. 19 (20.2%) patients developed grade /Ⅱ cardiotoxicity. There was no grade III/ cardiac event causing chemotherapy delay or break off. No further cardiotoxicity occurred neither during follow-up. CONCLUSION: PLD-containing first-line R-CDOP like regimen is demonstrated as a highly effective and much tolerable alternative for DLBCL patients with cardiovascular diseases/risk factors.
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Context: In platinum-resistant ovarian cancer, single-agent chemotherapy is recommended for the reduction of adverse events. However, in clinical practice, some patients can tolerate drug-specific adverse events. Aims: We assessed the safety of pegylated liposomal doxorubicin (PEG-LD) and docetaxel regimen in the first cycle of ovarian cancer. Settings and Design: We performed a phase I study to evaluate the combination therapy of PEG-LD and docetaxel. Materials and Methods: We recruited five patients with recurrent ovarian cancer within 12 months of first-line platinum-based chemotherapy. All patients had measurable disease severity. PEG-LD and docetaxel were intravenously administered on day 1 and every 21 days using three dose levels: 25 mg/m2 PEG-LD and 50 mg/m2 docetaxel; 30 mg/m2 PEG-LD and 50 mg/m2 docetaxel; and 30 mg/m2 PEG-LD and 60 mg/m2 docetaxel. Statistical Analysis Used: We defined the maximum tolerated dose of the combination therapy based on the modified Fibonacci method. Results: Five patients were enrolled in this study. The median treatment-free interval was 5.5 months. Two dose-limiting toxicities (Grade 4 neutropenia) were observed in two patients. One complete response, one partial response, one stable disease, and two progressive disease cases were observed. The overall response rate was 2/5, and the disease control rate was 3/5. The median overall survival was 7.4 months. Conclusions: We determined that 25 mg/m2 of PEG-LD and 50 mg/m2 of docetaxel were safe and effective doses. This preliminary efficacy and safety data should be further investigated in a Phase II trial.
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Objective:To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in CHOP regimen for un-treated elderly patients with advanced diffuse large B-cell lymphoma (DLBCL). Methods:In a prospective phase II study, we analyzed the feasibility of PLD-modified CHOP regimen in elderly patients with advanced stages of DLBCL. PLD was administered at 30 mg/m2 in combination with cyclophosphamide, vincristine, and prednisone at standard doses every 21 d for six cycles. CD20 positive patients were given option for rituximab treatment. Results:From November 2011 to March 2014, 30 patients with a median age of 70 years (range:63 to 80) were enrolled in this study. Up to 24 cases (80.0%) obtained an International Prognostic Index of≥3. The overall re-sponse rate was 86.7%, and the complete remission rate was 66.7%. With a median follow-up of 20.1 months, the 18-month overall and progression-free survival rates were 82.4%and 70.1%, respectively. The main toxicity was neutropenia, reaching grades 3 to 4 in the 24 cases (80.0%). No significant changes existed in patients' left ventricular ejection fraction and serum troponin-T during the study. Four patients (13.3%) showed asymptomatic abnormal changes in electrocardiogram after PLD infusion. Conclusion:CHOP regimen with PLD is an effective alternative for the treatment of DLBCL in elderly patients, exhibiting an acceptable toxicity.
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OBJECTIVE: To investigate the pharmacokinetics of pegylated liposomal doxorubicin (PLD) in Chinese tumor patients. METHODS: Ten patients with malignant tumors were given PLD (20-35 mg · m-2) combined chemotherapy. Serial plasma samples were obtained after completion of the infusion. The doxorubicin concentrations in plasma were measured using high-performance liquid chromatography (HPLC). The pharmacokinetic parameters were estimated by DAS software. The correlations between those parameters and gender were analyzed. RESULTS: The doxorubicin plasma concentration in the 10 patients ranged from 1.68 to 10.10 mg · L-1 during 0 - 168 h after administration. The AUC0-∞, CL, t1/2 and Vd were (918.6 ± 447.4) mg · L · h-1, (0.037 ± 0.02) L · h · m-2, (64.9 ± 28.4) h and (2.95 ± 0.88) L · m-2, respectively. The differences of the pharmacokinetic parameters, ie AUC0-∞, CL, t1/2 and Vd, between genders were not statistically significant. CONCLUSION: The pharmacokinetics of PLD fits one-compartment model, with long retention time, low clearance and small volume of distribution. Copyright 2012 by the Chinese Pharmaceutical Association.