Panitumumab and Pegylated Liposomal Doxorubicin in Platinum-Resistant Epithelial Ovarian Cancer With KRAS Wild-Type: The PaLiDo Study, a Phase II Nonrandomized Multicenter Study

2013 ◽  
Vol 23 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Karina Dahl Steffensen ◽  
Marianne Waldstrøm ◽  
Niels Pallisgård ◽  
Bente Lund ◽  
Kjell Bergfeldt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Confidence Interval ◽  
Liposomal Doxorubicin ◽  
Response Rate ◽  
Pegylated Liposomal Doxorubicin ◽  
Skin Toxicity ◽  
Wild Type ◽  
Intention To Treat ◽  
Platinum Resistant ◽  
Treat Population

ObjectiveThe increasing number of negative trials for ovarian cancer treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may improve survival. The aim of this study was to investigate the response rate in platinum-resistant, KRAS wild-type ovarian cancer patients treated with pegylated liposomal doxorubicin (PLD) supplemented with panitumumab.Patients and MethodsMajor eligibility criteria were relapsed ovarian/fallopian/peritoneal cancer patients with platinum-resistant disease, measurable disease by GCIG CA125 criteria and KRAS wild-type. Patients were treated with panitumumab 6 mg/kg day 1 and day 15 and with PLD 40 mg/m2day 1, every 4 weeks.ResultsForty-six patients were enrolled by 6 study sites in this multi-institutional phase II trial. The response rate in the intention-to-treat population (n = 43) was 18.6%. Progression-free and overall survival in the intention-to-treat population was 2.7 months (2.5–3.2 months, 95% confidence interval) and 8.1 months (5.6–11.7 months, 95% confidence interval), respectively. The most common treatment-related grade 3 toxicities included skin toxicity (42%), fatigue (19%), and vomiting (12%).ConclusionsThe combination of PLD and panitumumab demonstrates efficacy in platinum refractory/resistant patients but the skin toxicity was considerable.

Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with KRAS wild-type: The PaLiDo study, a phase II nonrandomized multicenter study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5052-5052 ◽  
Author(s):  
Karina Dahl Steffensen ◽  
Marianne Waldstrøm ◽  
Niels Pallisgaard ◽  
Bente Lund ◽  
Kjell Bergfeldt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Response Rate ◽  
Pegylated Liposomal Doxorubicin ◽  
Ca 125 ◽  
Wild Type ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy ◽  
Dermatologic Toxicity

5052 Background: Ovarian cancer (OC) patients with platinum-resistant recurrent disease have few therapeutic options and the response rates are only 10-20% using non-cross-resistant chemotherapeutic agents. The increasing number of negative trials for OC treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may result in improvement in survival. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). No previous studies have evaluated the effect of panitumumab in OC based on KRAS mutation status. The main purpose was to investigate the response rate in platinum-resistant, KRAS wild-type OC patients treated with pegylated liposomal doxorubicin (PLD) supplemented with panitumumab. Methods: Major eligibility criteria were confirmed stage I-IV primary epithelial ovarian/fallopian/peritoneal cancer patients with progression either during or within 6 months after end of first or second line platinum-based chemotherapy. Only patients with measurable disease by CA125 criteria and with KRAS wild type were eligible. Patients were treated with panitumumab 6 mg/kg day 1 and day 15 and with PLD 40 mg/m² day 1, every 4 weeks. Tumor assessment was performed at baseline and at every third cycle according to CA-125 criteria. Results: A total of 46 patients were enrolled by 6 study sites in this multi-institutional phase II trial. Within the population evaluable for response (N=33), there was 8 CA125 responders for an overall response rate of 24.3 %. Progression-free and overall survival in the intention-to-treat population (N=43) was 2.7 months (2.5-3.2 months, 95%CI) and 8.1 months (5.6-11.7 months, 95%CI), respectively. The most common treatment related grade 3 toxicities included skin toxicity (42%), fatigue (19%) and vomiting (12%). Conclusions: The combination of PLD and panitumumab demonstrates efficacy in platinum refractory/resistant patients although the dermatologic toxicity was considerable.

scholarly journals Extracorporeal Elimination of Circulating Pegylated Liposomal Doxorubicin (PLD) to Enhance the Benefit of Cytostatic Therapy in Platinum-Resistant Ovarian Cancer Patients

2015 ◽  
Vol 58 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Ondřej Kubeček ◽  
Milan Bláha ◽  
Daniel Diaz-Garcia ◽  
Stanislav Filip
Keyword(s):  
Ovarian Cancer ◽  
Metastatic Disease ◽  
Liposomal Doxorubicin ◽  
Tumor Tissue ◽  
Pegylated Liposomal Doxorubicin ◽  
Skin Toxicity ◽  
Liposomal Form ◽  
Female Population ◽  
Platinum Resistant ◽  
Treatment Tolerance

Ovarian cancer is the fifth most common malignancy in the world’s female population and with the highest lethality index among gynecological tumors. The prognosis of metastatic disease is usually poor, especially in platinum-resistant cases. There are several options for the treatment of metastatic disease resistant to platinum derivates (e.g. paclitaxel, topotecan and pegylated liposomal doxorubicin), all of which are considered equipotent. Pegylated liposomal doxorubicin (PLD) is a liposomal form of the anthracycline antibiotic doxorubicin. It is characterized by more convenient pharmacokinetics and a different toxicity profile. Cardiotoxicity, the major adverse effect of conventional doxorubicin, is reduced in PLD as well as hematotoxicity, alopecia, nausea and vomiting. Skin toxicity and mucositis, however, emerge as serious issues since they represent dose and schedule-limiting toxicities. The pharmacokinetics of PLD (prolonged biological half-life and preferential distribution into tumor tissue) provide new possibilities to address these toxicity issues. The extracorporeal elimination of circulating liposomes after PLD saturation in the tumor tissue represents a novel and potent strategy to diminish drug toxicity. This article intends to review PLD characteristics and the importance of extracorporeal elimination to enhance treatment tolerance and benefits.

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.

Randomized Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer

2007 ◽  
Vol 25 (19) ◽  
pp. 2811-2818 ◽  
Author(s):  
David G. Mutch ◽  
Mauro Orlando ◽  
Tiana Goss ◽  
Michael G. Teneriello ◽  
Alan N. Gordon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Single Agent ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Therapeutic Index ◽  
Phase Iii ◽  
End Points ◽  
Platinum Resistant ◽  
Significant Difference

Purpose Ovarian cancer (OC) patients experiencing progressive disease (PD) within 6 months of platinum-based therapy in the primary setting are considered platinum resistant (Pt-R). Currently, pegylated liposomal doxorubicin (PLD) is a standard of care for treatment of recurrent Pt-R disease. On the basis of promising phase II results, gemcitabine was compared with PLD for efficacy and safety in taxane-pretreated Pt-R OC patients. Patients and Methods Patients (n = 195) with Pt-R OC were randomly assigned to either gemcitabine 1,000 mg/m2 (days 1 and 8; every 21 days) or PLD 50 mg/m2 (day 1; every 28 days) until PD or undue toxicity. Optional cross-over therapy was allowed at PD or at withdrawal because of toxicity. Primary end point was progression-free survival (PFS). Additional end points included tumor response, time to treatment failure, survival, and quality of life. Results In the gemcitabine and PLD groups, median PFS was 3.6 v 3.1 months; median overall survival was 12.7 v 13.5 months; overall response rate (ORR) was 6.1% v 8.3%; and in the subset of patients with measurable disease, ORR was 9.2% v 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea/vomiting, fatigue, and neutropenia but not febrile neutropenia. Conclusion Although this was not designed as an equivalency study, gemcitabine and PLD seem to have a comparable therapeutic index in this population of Pt-R taxane-pretreated OC patients. Single-agent gemcitabine may be an acceptable alternative to PLD for patients with Pt-R OC.

Phase II study of vinorelbine in patients with pretreated advanced ovarian cancer: activity in platinum-resistant disease.

1996 ◽  
Vol 14 (9) ◽  
pp. 2546-2551 ◽  
Author(s):  
E Bajetta ◽  
A Di Leo ◽  
L Biganzoli ◽  
L Mariani ◽  
F Cappuzzo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Confidence Interval ◽  
Cancer Patients ◽  
Response Rate ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Ca 125 ◽  
Resistant Disease ◽  
Platinum Resistant ◽  
Exact Confidence Interval

PURPOSE The aim of the study was to evaluate the activity of vinorelbine (VNLB) in a population of advanced ovarian cancer patients, with particular attention to defining its role in platinum-resistant disease. PATIENTS AND METHODS Thirty-three patients were recruited and treated with VNLB 25 mg/m2 intravenously (IV) weekly. the median age was 53 years, performance status 0 to 2, and number of previous chemotherapy regimens two (range, one to five). Twenty-four patients were platinum-resistant; the remaining nine either were platinum-sensitive (four cases) or had undetermined sensitivity (five cases). RESULTS The mean delivered dose-intensity of VNLB was 67% of the planned level, because 60% of the cycles were delayed due to neutropenia or anemia. Four partial responses (PRs) and one complete response (CR) were observed, for an overall response rate of 15% (95% exact confidence interval, 5.1% to 31.9%). All the responses occurred in the subgroup of 24 platinum-resistant cases, in whom the response rate was 21% (95% exact confidence interval, 7.1% to 42.1%). Seven patients became stabilized on VNLB, and 27% of the cases showed a reduction in serum cancer antigen 125 (CA 125) levels. G3/G4 side effects consisted of neutropenia, anemia, and worsening of preexisting peripheral neuropathy. No treatment-related deaths occurred. CONCLUSION VNLB led to a 21% response rate in the population of heavily pretreated and platinum-resistant ovarian cancer patients. Further studies of VNLB alone or in combination with taxanes are warranted in patients with less pretreatment.

Combined pembrolizumab and pegylated liposomal doxorubicin in platinum resistant ovarian cancer: A phase 2 clinical trial

2020 ◽  
Vol 159 (1) ◽  
pp. 72-78
Author(s):  
Elizabeth K. Lee ◽  
Niya Xiong ◽  
Su-Chun Cheng ◽  
William T. Barry ◽  
Richard T. Penson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase 2 ◽  
Platinum Resistant ◽  
Phase 2 Clinical Trial

scholarly journals Phase 1/2 Study of Atrasentan Combined with Pegylated Liposomal Doxorubicin in Platinum-Resistant Recurrent Ovarian Cancer

Neoplasia ◽  
2010 ◽  
Vol 12 (11) ◽  
pp. 941-IN20 ◽  
Author(s):  
Petronella O. Witteveen ◽  
Koen J.C. van der Mijn ◽  
Maartje Los ◽  
Roelien H. Kronemeijer ◽  
Gerard Groenewegen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Phase 1 ◽  
Pegylated Liposomal Doxorubicin ◽  
Recurrent Ovarian Cancer ◽  
Platinum Resistant
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