Pegylated liposomal doxorubicin HCL (PLD; Caelyx/Doxil®): Experience with long-term maintenance in responding patients with recurrent epithelial ovarian cancer

Andreopoulou, Eleni; Gaiotti, Darci; Kim, E; Downey, Andrea; Mirchandani, D.; Hamilton, Anne; Jacobs, A.; Curtin, John P.; Fm, Muggia

doi:10.1093/annonc/mdl484

Cited by 72 publications

(36 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…35 In order to induce specific cytotoxic impacts solely in cancer cells within the TME, we aimed to harness both passive and active targeting mechanisms by engineering SHK-loaded PLGA NPs armed with TEM1-targeting Ab/scFv.…”

mentioning

confidence: 99%

Shikonin-loaded antibody-armed nanoparticles for targeted therapy of ovarian cancer

Barar

Sandaltzopoulos

Liu

et al. 2014

IJN

View full text Add to dashboard Cite

Conventional chemotherapy of ovarian cancer often fails because of initiation of drug resistance and/or side effects and trace of untouched remaining cancerous cells. This highlights an urgent need for advanced targeted therapies for effective remediation of the disease using a cytotoxic agent with immunomodulatory effects, such as shikonin (SHK). Based on preliminary experiments, we found SHK to be profoundly toxic in ovarian epithelial cancer cells (OVCAR-5 and ID8 cells) as well as in normal ovarian IOSE-398 cells, endothelial MS1 cells, and lymphocytes. To limit its cytotoxic impact solely to tumor cells within the tumor microenvironment (TME), we aimed to engineer SHK as polymeric nanoparticles (NPs) with targeting moiety toward tumor microvasculature. To this end, using single/double emulsion solvent evaporation/diffusion technique with sonication, we formulated biodegradable NPs of poly(lactic-co-glycolic acid) (PLGA) loaded with SHK. The surface of NPs was further decorated with solubilizing agent polyethylene glycol (PEG) and tumor endothelial marker 1 (TEM1)/endosialin-targeting antibody (Ab) through carbodiimide/N-hydroxysuccinimide chemistry. Having characterized the physicochemical and morphological properties of NPs, we studied their drug-release profiles using various kinetic models. The biological impact of NPs was also evaluated in tumor-associated endothelial MS1 cells, primary lymphocytes, and epithelial ovarian cancer OVCAR-5 cells. Based on particle size analysis and electron microscopy, the engineered NPs showed a smooth spherical shape with size range of 120 to 250 nm and zeta potential value of −30 to −40 mV. Drug entrapment efficiency was ~80%–90%, which was reduced to ~50%–60% upon surface decoration with PEG and Ab. The liberation of SHK from NPs showed a sustained-release profile that was best fitted with Wagner log-probability model. Fluorescence microscopy and flow cytometry analysis showed active interaction of Ab-armed NPs with TEM1-positive MS1 cells, but not with TEM1-negative MS1 cells. While exposure of the PEGylated NPs for 2 hours was not toxic to lymphocytes, long-term exposure of the Ab-armed and PEGylated NPs was significantly toxic to TEM1-positive MS1 cells and OVCAR-5 cells. Based on these findings, we propose SHK-loaded Ab-armed PEGylated PLGA NPs as a novel nanomedicine for targeted therapy of solid tumors.

show abstract

mentioning

confidence: 99%

Shikonin-loaded antibody-armed nanoparticles for targeted therapy of ovarian cancer

Barar

Sandaltzopoulos

Liu

et al. 2014

IJN

View full text Add to dashboard Cite

show abstract

“…The development of secondary malignancies, predominantly lymphomas but also including oral cavity SCC, has been recognized with PLD use for Kaposi sarcoma [9]. Because PLD is generally well tolerated, we deemed it suitable for long-term maintenance in patients treated using our protocols for recurrent ovarian cancer [10]. In fact, in that report, we noted that seven patients continued on maintenance PLD beyond 4 years without cumulative cardiac toxicity.…”

Section: Introductionmentioning

confidence: 93%

“…The associated lower incidence of cardiotoxicity [8] makes it an attractive option for the treatment of patients with various malignancies that are considered sensitive to anthracyclines. PLD is approved for use in patients with Kaposi sarcoma [9], platinum-resistant recurrent ovarian cancer [10], and multiple myeloma. Recently, the combination of carboplatin and PLD was shown to lead to a longer progression-free survival interval in patients with platinum-sensitive recurrences, when compared with carboplatin and paclitaxel [11].…”

Section: Introductionmentioning

confidence: 99%

Squamous Cell Carcinoma of the Oral Cavity in Nonsmoking Women: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer?

Cannon¹,

Lai²,

Hirsch³

et al. 2012

The Oncologist

View full text Add to dashboard Cite

After completing this course, the reader will be able to:1. Compare the risk of secondary cancer versus benefits of maintenance therapy for women with ovarian cancer who have a complete response to pegylated liposomal doxorubicin.2. Explain the need to perform regular and frequent oral examinations in women with ovarian cancer who received treatment with pegylated liposomal doxorubicin.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTPurpose. To describe occurrences of oral squamous cell carcinoma (SCC) in patients who had received long-term pegylated liposomal doxorubicin (PLD) for ovarian cancer. Patients and Methods. In our cohort of patients on maintenance PLD for ovarian and related mullerian epithelial malignancies, we encountered two patients with invasive SCC of the oral cavity (one of them multifocal) and one with high-grade squamous dysplasia. Review of patients at our institution receiving PLD for recurrent ovarian cancer identified three additional patients. The duration of treatment, cumulative PLD dose, human papillomavirus (HPV) positivity, BRCA status, stage at diagnosis, outcome, and other characteristics are reviewed.Results. All five cases were nonsmokers with no known risk factors for HPV and four were negative for p16 expression. Four of the patients had known BRCA mutations whereas one tested negative. Cumulative doses of PLD were >1,600 mg/m 2 given over 30 -132 months. Three had SCCs staged as T1N0 oral tongue, alveolar ridge (gingival), and multifocal oral mucosa; one had a T2N0 oral tongue; and one had dysplasia. After excision, two were given radiation but recurred shortly thereafter; the others remain well and have had no further exposure to cytotoxic drugs, including PLD. Conclusion. Awareness of this possible long-term complication during PLD treatment should enhance the likelihood of early detection of oral lesions in these patients. Decisions to continue maintenance PLD after complete re-

show abstract

“…Its therapeutic applications are nevertheless limited by the strong cardiac and bone marrow toxicity. DOX effectiveness has been greatly improved when specific targeting at the tumour sites has been achieved, for instance by loading the drug into liposomes (e.g., Caelyx ® /Doxil ® ) [42,43]. DOX was loaded in the previously described PLGA-ALE NPs and the anti-tumour effect of the carrier was assessed in vitro and in vivo [44].…”

Section: Drug-loaded Nanoparticlesmentioning

confidence: 99%

PLGA-Alendronate Conjugate as a New Biomaterial to Produce Osteotropic Drug Nanocarriers

Pignatello¹

2011

Biomaterials Applications for Nanomedicine

View full text Add to dashboard Cite

Pegylated liposomal doxorubicin HCL (PLD; Caelyx/Doxil®): Experience with long-term maintenance in responding patients with recurrent epithelial ovarian cancer

Abstract: PLD appears to be safe as long-term maintenance in ovarian cancer and may be important for a continued response.

Cited by 72 publications

References 30 publications

Shikonin-loaded antibody-armed nanoparticles for targeted therapy of ovarian cancer

Shikonin-loaded antibody-armed nanoparticles for targeted therapy of ovarian cancer

Squamous Cell Carcinoma of the Oral Cavity in Nonsmoking Women: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer?

PLGA-Alendronate Conjugate as a New Biomaterial to Produce Osteotropic Drug Nanocarriers

Contact Info

Product

Resources

About