Pegylated liposomal doxorubicin and platinum in patients with advanced ovarian cancer in late relapse (>6 months)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15035-15035
Author(s):  
L. Wei ◽  
C. Chen ◽  
C. Huang ◽  
S. Chien ◽  
Y. Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Median Time ◽  
Advanced Ovarian Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Complete Response ◽  
Ca 125 ◽  
Cross Resistance ◽  
Late Relapse ◽  
Open Label ◽  
Overall Response

15035 Background: Platinum and doxorubicin have different mechanisms of action, show no cross-resistance, and their toxicities do not overlap. Because pegylated liposomaI doxorubicin (Lipo-Dox was manufactured by TTY Biopharm Company Ltd. in Taiwan) appears to be a promising form of delivering doxorubicin with decrease of some of the most problematic toxicities, a combination with platinum should be assessed. Methods: An open-label, non-comparative, single center phase II clinical trial. Eligible patients must have histologically proven advance ovarian cancer with two-dimensioned measurable disease or evaluable disease (defined as CA-125 ≥ 40 U/ml), who have been treated with one or two previous platinum- and taxane-based regimen. All patients will hospitalize for 24 hours for treatment. The dose of platinum is fixed (cisplatin at 75 mg/m2 or carboplatin at AUC=5) on D1 and the initial dose of pegylated liposomaI doxorubicin (Lipo-Dox) is 35 mg/m2 on D2 at a 4-week interval. Results: Twenty patients were enrolled from July 2002 to January 2004 and follow up until June 2004. All eligible patients are assessable for response and toxicity. The overall response rate was 80%. Of the 20 patients eligible for response evaluation, 10 (50%) patients had a complete response, 6 (30%) had partial response, 3 (15%) were with stable disease, and 1 (5%) showed progressive disease. An overall response (OR) was achieved in 80% of patients. In patients achieving an OR based on WHO criteria, median CA125 levels declined from 142 U/ml (range, 13–3670 U/ml) during the baseline to 26.5 U/ml (range, 5–375 U/ml) during the last cycle. Median time to response was 65 days (range, 12–188 days). Median duration of response was 471 days (range 146–1085 days). Furthermore, the median time to progression was 481 days (range, 138–1136 days). The main toxicity was myelosuppression, with grade 3 and 4 neutropenia in 3 patients, anemia in 4 patients, and leukopenia in 2 patients. Conclusions: Based on effectiveness and toxicity advantages, the combination of pegylated liposomaI doxorubicin (Lipo-Dox) and platinum should be considered in patients with advanced ovarian cancer in late relapse. No significant financial relationships to disclose.

Correlation of CA-125 and RECIST evaluation in recurrent ovarian cancer (ROC): Results from a randomized phase III study of trabectedin (T) with pegylated liposomal doxorubicin (PLD) versus PLD alone

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5550-5550
Author(s):  
T. J. Herzog ◽  
J. B. Vermorken ◽  
E. Pujade-Lauraine ◽  
J. Li ◽  
E. Bayever ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Predictive Value ◽  
Objective Response ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Ca 125 ◽  
Open Label ◽  
Significant Prolongation ◽  
Phase Iii Study ◽  
The Impact

5550 Background: OVA-301, an open-label, multicenter, randomized phase III study comparing the combination of T and PLD to PLD alone in 672 ovarian cancer patients, showed significant prolongation in Progression-Free Survival (PFS) and higher Objective Response (OR) in the combination arm (T-PLD) by three separate assessments, investigator assessment (IA), independent radiology (IR) and oncology review (IO). The purpose of this analysis is to examine: 1) the impact of early changes in CA-125 over the subsequent best OR by RECIST; 2) the concordance between best OR determined by CA-125 and RECIST; 3) the value of CA-125 to predict radiological response. Methods: Tumor assessments by imaging and CA-125 were performed at baseline, and every 8 weeks during study in both arms. Radiological tumor assessment, regardless of CA-125 changes, determined the study conduct. Early CA-125 changes were those assessed at the first and second evaluation. Analyses were based on “all randomized patients.” Results: Response rate by RECIST (IR)/CA-125 was 28%/48% for T-PLD vs. 19%/33% for PLD. The association between CA-125 and RECIST response was stronger for IA relative to IR/IO, with 79% concordance for both arms, 65% overall positive predictive value (PPV) and 89% negative predictive value (NPV) for IA and 74%/75% concordance, 46%/49% PPV and 93%/92% NPV for IR/IO. Early CA-125 changes were assessed in 514 patients. Early ≥25% CA-125 decreases in the first/second evaluation occurred in 85%/95% of RECIST responders in the T-PLD arm and in 81/82% responders treated with PLD. Conclusions: The predictive value of CA-125 response was high and similar in both arms. The addition of T to PLD resulted in superior efficacy in this patient population as assessed by IA, IR and IO, with a favorable trend for CA-125 response assessment. RECIST response was preceded by a significant CA-125 decrease in a high proportion of patients. [Table: see text]

Phase II Study of Carboplatin, Paclitaxel, and Bevacizumab With Maintenance Bevacizumab As First-Line Chemotherapy for Advanced Müllerian Tumors

2010 ◽  
Vol 28 (1) ◽  
pp. 154-159 ◽  
Author(s):  
Richard T. Penson ◽  
Don S. Dizon ◽  
Stephen A. Cannistra ◽  
Maria R. Roche ◽  
Carolyn N. Krasner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Area Under The Curve ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Ca 125 ◽  
Open Label ◽  
Peritoneal Cancer ◽  
Open Label Phase

Purpose New strategies are needed to improve outcomes for patients with advanced ovarian cancer. Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes vascular endothelial growth factor but is associated with GI perforations (GIPs) in patients with recurrent disease. Patients and Methods An open-label, phase II clinical trial was conducted in newly diagnosed patients with stage ≥ IC epithelial müllerian tumors. Patients received intravenous (IV) carboplatin (area under the curve = 5), paclitaxel (175 mg/m2 IV), and bevacizumab (15 mg/kg IV) for six to eight cycles on day 1 every 21 days. Bevacizumab was omitted in the first cycle and continued as a single agent for 1 year. Results Sixty-two women participated in this study. Fifty-one patients (82%) were optimally surgically cytoreduced before treatment. The median age was 58 years (range, 18 to 77 years). Forty-five women (73%) had ovarian cancer, 10 (16%) had peritoneal cancer, four (6%) had fallopian tube cancers, and three (5%) had uterine papillary serous tumors. The majority of patients (90%) had stage III or IV disease. A median of 17 maintenance cycles (range, 0 to 25+ cycles) of bevacizumab (556 cycles) were administered with mild toxicity. Treatment was associated with two pulmonary embolisms and two GIPs, all occurring during the chemotherapy phase of treatment (364 total cycles). No grade 4 toxicities were seen during maintenance bevacizumab treatment. Radiographic responses were documented in 21 (75%) of 28 women with measurable disease (11 complete responses and 10 partial responses), with CA-125 responses in 76% of patients (11 complete responses, 21%; and 35 partial responses, 55%). The progression-free survival rate at 36 months was 58%. Conclusion The regimen of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab is feasible, safe, and worthy of future study in advanced ovarian cancer.

Phase II Study of Pegylated Liposomal Doxorubicin and Carboplatin in Patients With Platinum-Sensitive and Partially Platinum-Sensitive Metastatic Ovarian Cancer

2009 ◽  
Vol 19 (6) ◽  
pp. 1137-1141 ◽  
Author(s):  
B. L. Rapoport ◽  
D. A. Vorobiof ◽  
C. Slabber ◽  
A. S. Alberts ◽  
H. S. Hlophe ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Median Time ◽  
Median Survival ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Phase Ii Study ◽  
Pegylated Liposomal Doxorubicin ◽  
Time To Progression ◽  
Overall Response ◽  
Platinum Sensitive

Objective:This phase II study assessed the activity and safety of pegylated liposomal doxorubicin (PLD) plus carboplatin in relapsed ovarian cancer (ROC).Method:Forty women with platinum-sensitive and partially platinum-sensitive ROC were treated with PLD 50 mg/m2plus carboplatin area under the curve 5 every 28 days in this South African multicenter study. All patients who completed 3 cycles of chemotherapy were evaluated for response. Primary outcome was response in the intent-to-treat population.Results:Complete response was 35%, and partial response was 32.5% (overall response, 67.5%). Median time-to-progression was 11.9 months, and median survival was 30.0 months. Overall response was higher in platinum-sensitive (81%) versus partially platinum-sensitive patients (53%), as were median duration of response, median time-to-progression, and median survival. Treatment was well tolerated, with no grade 4 nonhematologic toxicities. Grade 3/4 hematologic toxicities included leukopenia (58%), neutropenia (55%), and thrombocytopenia (43%).Conclusion:Pegylated liposomal doxorubicin plus carboplatin is well tolerated and active in the treatment of platinum-sensitive and partially platinum-sensitive ROC.

Carboplatin plus ifosfamide as salvage treatment of epithelial ovarian cancer: a pilot study.

1993 ◽  
Vol 11 (10) ◽  
pp. 1952-1956 ◽  
Author(s):  
V Lorusso ◽  
A Catino ◽  
B Leone ◽  
M Rabinovich ◽  
G Gargano ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Overall Response Rate ◽  
Response Rate ◽  
Advanced Ovarian Cancer ◽  
Complete Response ◽  
Salvage Treatment ◽  
Previous Response ◽  
Overall Response ◽  
Platinum Resistant

PURPOSE This study aimed to evaluate the activity and toxicity of carboplatin (PPL) and ifosfamide (IFO) in patients with epithelial ovarian cancer previously treated with cisplatin (CDDP)-containing regimens. PATIENTS AND METHODS From July 1989 to December 1991, 35 patients with epithelial ovarian cancer relapsed or refractory to CDDP as first-line chemotherapy were treated. PPL was administered at a dose of 300 mg/m2 intravenously (IV) on day 1 and IFO at a dose of 1,500 mg/m2 IV on days 1 to 3 every 3 to 4 weeks. Criteria for evaluating previous response to CDDP were strictly defined. RESULTS The overall response rate was 43% (complete response [CR], 6%; partial response [PR], 37%) and the median duration of response was 7 months (range, 3 to 16). In potentially platinum-sensitive (PPS; relapsed) patients, the overall response rate was 56%. None of the primary platinum-resistant (PPR) patients obtained a clinical response to PPL plus IFO, whereas one of five secondary platinum-resistant (SPR) patients obtained a PR. The regimen was easily manageable. CONCLUSION PPL plus IFO is useful and well-tolerated combination in salvage treatment of patients with advanced ovarian cancer. However, clear synergism between PPL and IFO that could overcome intrinsic or acquired CDDP resistance was not observed. The advantage of PPL plus IFO as compared with CDDP-containing regimens is represented by the increased tolerability and the reduced neurotoxicity, nephrotoxicity, and ototoxicity as compared with CDDP-containing regimens. It is essential that the patient population be defined according to their previous response to platinum therapy in trials involving second-line therapy of ovarian cancer.

Pretreatment CA-125 and Risk of Relapse in Advanced Ovarian Cancer

2006 ◽  
Vol 24 (9) ◽  
pp. 1454-1458 ◽  
Author(s):  
Maurie Markman ◽  
P.Y. Liu ◽  
Mace L. Rothenberg ◽  
Bradley J. Monk ◽  
Mark Brady ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Interaction Analysis ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Continuous Variable ◽  
Ca 125 ◽  
Maintenance Chemotherapy ◽  
Risk Of Relapse

Purpose A previous report suggested the nadir serum CA-125 level within the group of patients with ovarian cancer who achieved normalization of CA-125 accurately defined the risk of relapse. Using similar CA-125 subgroups, we sought to determine if the baseline CA-125 level before initiation of maintenance chemotherapy in women achieving a clinically-defined complete response to primary chemotherapy would be of prognostic value. Patients and Methods Patients included in this retrospective analysis had been treated on one of two previously reported trials of maintenance chemotherapy (three v 12-monthly cycles of paclitaxel; oral altretamine), with a baseline CA-125 level of ≤ 35 u/mL. Progression-free survival (PFS) from study entry was analyzed by the Cox regression model. Results The distribution of premaintenance baseline CA-125 levels for the 384 patients was 58%, 34%, and 8% for values of (A) ≤ 10 u/mL, (B) 11 to 20 u/mL, and (C) 21 to 35 u/mL, respectively. The baseline CA-125 was highly statistically significant, either as a categoric variable (P < .001) or as a continuous variable (P < .0001). Median PFS was 24 months, 17 months, and 7 months for groups (A), (B), and (C), respectively. There was no evidence the CA-125 effect differed by trial or treatment in an interaction analysis (P = .70). Conclusion The baseline CA-125 level before initiation of maintenance chemotherapy strongly predicts the risk of subsequent relapse. Patients with premaintenance baseline CA-125 values ≤ 10 u/mL have a superior PFS compared with higher levels in the normal CA-125 range.

Clinical Utility of CA-125 for Maintenance Therapy in the Treatment of Advanced Stage Ovarian Carcinoma

2009 ◽  
Vol 19 (2) ◽  
pp. 239-241 ◽  
Author(s):  
John P. Micha ◽  
Bram H. Goldstein ◽  
Mark A. Rettenmaier ◽  
John V. Brown ◽  
Cameron R. John ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Ovarian Carcinoma ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Complete Response ◽  
Ca 125 ◽  
Advanced Stage ◽  
Therapy Regimen ◽  
Platinum Based Chemotherapy

AbstractMaintenance therapy has been extensively studied to discern any prospective therapeutic advantage in the treatment of advanced stage ovarian carcinoma. The CA-125 assay may have prognostic benefit in determining whether this treatment regimen is appropriate for ovarian carcinoma patients who achieve a complete response to first-line therapy. We retrospectively documented the CA-125 levels of 2 advanced ovarian cancer patient groups who exhibited a clinically defined complete response to their primary induction therapy. Patients were then treated with a paclitaxel-based maintenance therapy regimen. The first group (group A; n = 13 patients) received 3 cycles of single-agent paclitaxel maintenance therapy, and the second group (group B; n = 13 patients) received 12 cycles of single-agent paclitaxel maintenance therapy. The premaintenance therapy CA-125 serum levels (<10 or ≥10 U/mL) of the 2 treatment groups were then retrospectively evaluated in an intragroup analysis to discern any relationship with progression-free survival (PFS) and overall survival. There was a statistically significantly relationship between the CA-125 levels (<10 U/mL) premaintenance therapy and PFS. The patients who had the lowest CA-125 levels exhibited the most favorable PFS results. Despite the limited sample size and nonrandomized nature of this study, these results are provocative and suggest that advanced ovarian cancer patients who achieve an excellent response to primary platinum-based chemotherapy with a CA-125 serum level less than 10 U/mL may be more amenable to the benefits of paclitaxel maintenance therapy.

scholarly journals Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

2021 ◽  
pp. JCO.21.00334
Author(s):  
Junzo Hamanishi ◽  
Nobuhiro Takeshima ◽  
Noriyuki Katsumata ◽  
Kimio Ushijima ◽  
Tadashi Kimura ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Overall Response Rate ◽  
Response Rate ◽  
Pegylated Liposomal Doxorubicin ◽  
Hazard Ratio ◽  
Open Label ◽  
Overall Response ◽  
Platinum Resistant ◽  
Duration Of Response

PURPOSE This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.

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