Pegylated Liposomal Doxorubicin Arm Research Articles

Phase III randomized trial of pegylated liposomal doxorubicin (PLD) plus carboplatin versus carboplatin in platinum-sensitive (PS) patients with recurrent epithelial ovarian or peritoneal carcinoma after failure of initial platinum-based chemotherapy: Southwest Oncology Group Protocol S0200

5551 Background: There is a continuing debate over the role of combination, platinum-based chemotherapy for PS, recurrent ovarian cancer (OC). Although this phase 3 trial was closed prematurely by the SWOG Data Safety and Monitoring Committee (DSMC) due to slow patient accrual, it provided provocative results nonetheless. Methods: Patients with recurrent stage III or IV OC, with a progression-free and platinum-free interval of 6- 24 months after completion of first-line platinum-based chemotherapy, and up to 12 courses of non-platinum containing chemotherapy or biologic therapy as consolidation treatment after the first-line regimen were eligible and observed for progression-free survival (PFS) and overall survival (OS). Patients were randomized to either IV PLD (30 mg/m2) plus IV carboplatin (AUC=5 mg/mL × min) once every 4 weeks (PLD arm) or IV carboplatin (AUC=5mg/ML × min) once every four weeks alone. Results: The PLD arm enrolled 31 patients and the carboplatin alone arm enrolled 30 for a total of 61 patients out of the 900 planned. The response rates were 67% (18/27) for the PLD arm and 32% (9/28) for the carboplatin only arm (Fisher’s exact p=0.02). The estimated median PFS on the PLD arm was 12 months and 8 months on the carboplatin only arm. The estimated median OS on the PLD arm was 26 months and 18 months on the carboplatin only arm (p=0.02). 26% of the patients on the PLD arm reported grade 4 toxicities, all hematological in nature. Conclusions: Although this study was closed early, because of slow patient accrual the results for the PLD arm are intriguing for response rates, median progression-free survival and overall survival. These data suggest that there may be an advantage to the PLD plus carboplatin combination treatment in patients with PS, recurrent disease. No significant financial relationships to disclose.

A randomized phase III study of gemcitabine (GEM) versus pegylated liposomal doxorubicin (PLD) in progressive/recurrent ovarian cancer (OC)

LBA5506 Background: This multi-center Phase III study was designed to compare the efficacy and safety of PLD vs GEM in ovarian cancer (OC) patients relapsing within 12 months from platinum/paclitaxel treatment. Methods: Recurrent OC patients failing only one line of platinum/paclitaxel regimen with a platinum-free interval (PFI) ≤12 months, and with measurable or evaluable disease were eligible. Patients were randomized to receive PLD 40 mg/m2 d1 over 1 hr q 4 wk versus GEM 1,000 mg/m2 d1,8,15 over 30 min q 4 wk. The primary endpoint was time to progression (TTP), with overall survival (OS), overall response rate (ORR), safety/toxicity, and quality of life (QoL) as secondary endpoints. A total of 147 patients was calculated to be required (alpha=0.05, beta=0.80) in order to detect an increase in median TTP from 12 to 19 weeks in control (PLD) versus experimental (GEM) arm. Results: As of December 2006, 147 patients were enrolled; 74 and 73 patients were randomized to PLD versus GEM, respectively: overall, median age was 65 yrs (range 28–80); 69 (46.9%) patients had a PFI < 6 months, while 78 (53.1%) had a PFI between 6–12 months. response evaluation was possible in 129 cases: in PLD arm, the ORR was 15.9%, compared to an ORR=28.3% in GEM arm, p value=0.13). With a median follow up of 9 months, there was no difference in TTP between PLD and GEM arms (median TTP=16 versus 20 weeks, respectively; p value=0.44). Median OS was 56 weeks in PLD patients versus 50 weeks in GEM arm (p value=0.17). Total number of cycles was 301 in PLD arm, and 275 in GEM arm. Grade 3–4 leukopenia was documented in 8.7% of patients allocated to PLD versus 22.0% of patients administered GEM (p value=0.03); no difference in the distribution of severe anemia and thrombocytopenia was observed. There was no difference in non hematological toxicity. A total of 121 patients were considered for QoL data analysis: a trend to a better global QoL score was documented in PLD arm. (p value=0.015) Conclusions: PLD and GEM show similar activity in OC recurring within 12 months from primary treatment. No significant financial relationships to disclose.

Cost-minimization analysis of pegylated liposomal doxorubicin versus topotecan for the treatment of ovarian cancer in Italy

Background: Ovarian cancer is the most prevalent gynecologic cancer in women. Unfortunately for patients whose cancer is resistant to first-line therapies (platinum and paclitaxel), only a few second-line regimens have both significant efficacy and minimal treatment-related toxicity. Furthermore, the use of these agents increases treatment costs due to adverse events (AEs) related to tolerability and toxicity. Objective: The aim of the present study was to assess the comparative patient-specific treatment costs associated with 2 second-line therapies, both benchmark therapies used to treat ovarian cancer patients in Italy: pegylated liposomal doxorubicin (PLD) and topotecan, which appear to have similar efficacy but different tolerability and toxicity profiles. Methods: A cost-minimization analysis was performed in line with the point of view of Italy's National Health Service. Data on treatment efficacy and the number and types of AEs associated with drug toxicity were taken from a recent Phase III clinical trial comparing PLD with topotecan for the treatment of ovarian cancer. Resource-use estimates for each AE were based on the opinions of a panel of experts (Delphi method). Unit costs were drawn from national sources and a sensitivity analysis was performed. Results: The mean total per-patient cost in the PLD arm was €8812 (minimum, €8281; maximum, €9314) compared with €15,788 in the topotecan arm (minimum €12,014; maximum €18,847). The higher acquisition cost of PLD offset the higher cost of managing the AEs related to treatment with topotecan. Conclusions: The present analysis suggested the net cost-saving capability of PLD compared with topotecan. PLD required fewer ambulatory care-center visits for treatment administration and was associated with fewer severe AEs than topotecan.

Effect of Treatment on Health-Related Quality of Life in Acquired Immunodeficiency Syndrome (AIDS)-Related Kaposi's Sarcoma: A Randomized Trial of Pegylated-Liposomal Doxorubicin Versus Doxorubicin, Bleomycin, and Vincristine

The purpose of this study was to determine whether health-related quality of life (HRQL) would be improved in patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma treated by pegylated-liposomal doxorubicin (PLD) as compared to those treated by a conventional combination of doxorubicin, bleomycin, and vincristine (ABV). One hundred thirty-three patients received PLD and 125 patients received ABV every 2 weeks with a planned total of 6 cycles. Patients completed a 30-item AIDS-related HRQL questionnaire before beginning treatment (baseline), every 2 weeks while on treatment, and about 21 days after the end of treatment. Twenty-two items, involving nine domains, were analyzable. While on treatment, PLD-treated patients with partial clinical responses achieved statistically significant greater improvement (compared to baseline) in general health than did ABV-treated patients with partial clinical responses (ρ = 0.008). By the end of treatment, the overall group of patients receiving PLD showed statistically significant greater improvement in pain and energy/fatigue than did the group receiving ABV (ρ = 0.01–0.002). In addition, duration of clinically significant improvement in global QL was longer in the PLD arm.