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Liposomal Doxorubicin (liposomal + doxorubicin)
Kinds of Liposomal Doxorubicin Selected AbstractsPharmaceutical and Biomedical Differences between Micellar Doxorubicin (NK911) and Liposomal Doxorubicin (Doxil)CANCER SCIENCE, Issue 10 2002Yoshihisa Tsukioka The stability and biological behavior of an in vitro system of doxorubicin (DXR) entrapped in NK911, polymer micelles, was examined and compared with those of DXR entrapped in Doxil, polyethylene-glycol-conjugated liposomes. The fluorescence of DXR inside micelles or liposomes in an aqueous solution is known to be strongly quenched by the outer shells of the micellar or liposomal formation. Thus, by measuring the fluorescence intensity of DXR released from NK911 or Doxil, we could determine the stability of the micellar or liposomal DXR formation. Furthermore, NK911 was found to be less stable than Doxil in saline solution. In drug distribution experiments using an in vitro solid tumor model, when spheroids formed from two human colonic cancer lines, HT-29 and WiDr, and a human stomach cancer line, MKN28, were exposed to NK911, DXR was distributed throughout the spheroids, including their center. On the other hand, when the spheroids were exposed to Doxil, DXR was distributed only to the surface of the spheroids. It has been suggested that Doxil can deliver DXR to a solid tumor more efficiently than NK911 via the EPR (enhanced permeability and retention) effect, because Doxil may be more stable in plasma than NK911. On the other hand, DXR packed in NK911 may be distributed by diffusion to cancer cells distant from the tumor vessel, because NK911 can leak out of the tumor vessel and may be able to release free DXR more easily than Doxil. It has been suggested that drug carrier systems such as liposomes and micelles should be selected appropriately bearing in mind the characteristics of the tumor vasculature and the tumor interstitium. [source] Controlled application and removal of liposomal therapeutics: Effective elimination of pegylated liposomal doxorubicin by double-filtration plasmapheresis in vitroJOURNAL OF CLINICAL APHERESIS, Issue 2 2010Gerhard Pütz Abstract Introduction: Nanoscale particle-based drug delivery systems like long circulating liposomal doxorubicin show unique pharmacokinetic properties and improved toxicity profiles. Liposomal doxorubicin accumulates in tumor tissue due to the enhanced permeation and retention effect, but only a small fraction of a total dose reaches the tumor site. Accumulation of liposomal doxorubicin is much faster in tumor sites than in certain organs where dose limiting adverse effects occur. Finding a way to detoxify the predominant part of a given dose, circulating in the blood after accumulation is completed, will presumably reduce severe side effects during chemotherapy. Methods: Elimination properties of therapeutic used pegylated liposomal doxorubicin (Doxil®/Caelyx®) and therapeutic used double-filtration plasmapheresis systems were evaluated in vitro and in reconstituted human blood. Results: Liposomes can be filtered by appropriate membranes without leakage of doxorubicin up to a pressure of 1 bar. At higher pressures, liposomes (,85 nm) may squeeze through much smaller pores without significant leakage of doxorubicin, whereas decreasing pore size to ,8 nm leads to increased leakage of doxorubicin. With therapeutic used apheresis systems, liposomal doxorubicin can be efficiently eliminated out of buffer medium and reconstituted human blood. No leakage of doxorubicin was detected, even when liposomes were circulating for 48 h in human plasma before apheresis. Conclusions: Convenient apheresis techniques are capable of a safe and efficient elimination of therapeutic used liposomal doxorubicin in an experimental model system. J. Clin. Apheresis, 2010. © 2010 Wiley-Liss, Inc. [source] Delayed complete remission in a patient with multiple myelomaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2008R. Ria Abstract We report a strikingly positive, late response to bortezomib in conjunction with pegylated liposomal doxorubicin in a 79-year old woman with multiple myeloma (MM). The patient obtained a partial remission after eight courses of therapy and a complete remission about 10 months after the end of therapy. This delayed complete remission may be similar to the spontaneous regression reported for other malignancies such as melanoma or lymphoma. We postulate that the immune response and a persistent anti-angiogenic effect of bortezomib could well explain the delayed complete remission in our patient. [source] Therapy of metastasized Merkel cell carcinoma with liposomal doxorubicin in combination with radiotherapyJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 6 2009Marion Wobser Summary Background: Merkel cell carcinoma is a rare skin cancer of neuroendocrine origin, which is characterized by a high rate of recurrence, metastatic spread and mortality. Because of its rarity, evidence-based therapeutic regimens are difficult to establish. Merkel cell carcinoma is known to be both radio- and chemosensitive. Toxicity is a key factor in assessing any regimen, as the patients are usually elderly and likely to have other significant medical problems. Patients and Methods: We retrospectively evaluated five patients with metastatic Merkel cell carcinoma to see if liposomal doxorubicin (Caelyx® or Myocet®) in combination with radiotherapy exhibited clinical anti-tumoral effects accompanied by acceptable side effects. Results: The outpatient chemotherapy regimen was tolerated without major side effects and produced good response rates. All patients achieved at least tumor stabilization; four of five had a partial remission. Effects of therapy were usually seen in the first cycle of therapy but the responses were of short duration with an average interval of two months until progression. Conclusions: As combined radiochemotherapy with liposomal doxorubicin is well tolerated even in older patients with other illnesses and can be given on an outpatient basis, it is an attractive option for metastatic Merkel cell carcinoma. Based on response rate or overall survival, it offers no advantages compared to polychemotherapy. [source] Controlled application and removal of liposomal therapeutics: Effective elimination of pegylated liposomal doxorubicin by double-filtration plasmapheresis in vitroJOURNAL OF CLINICAL APHERESIS, Issue 2 2010Gerhard Pütz Abstract Introduction: Nanoscale particle-based drug delivery systems like long circulating liposomal doxorubicin show unique pharmacokinetic properties and improved toxicity profiles. Liposomal doxorubicin accumulates in tumor tissue due to the enhanced permeation and retention effect, but only a small fraction of a total dose reaches the tumor site. Accumulation of liposomal doxorubicin is much faster in tumor sites than in certain organs where dose limiting adverse effects occur. Finding a way to detoxify the predominant part of a given dose, circulating in the blood after accumulation is completed, will presumably reduce severe side effects during chemotherapy. Methods: Elimination properties of therapeutic used pegylated liposomal doxorubicin (Doxil®/Caelyx®) and therapeutic used double-filtration plasmapheresis systems were evaluated in vitro and in reconstituted human blood. Results: Liposomes can be filtered by appropriate membranes without leakage of doxorubicin up to a pressure of 1 bar. At higher pressures, liposomes (,85 nm) may squeeze through much smaller pores without significant leakage of doxorubicin, whereas decreasing pore size to ,8 nm leads to increased leakage of doxorubicin. With therapeutic used apheresis systems, liposomal doxorubicin can be efficiently eliminated out of buffer medium and reconstituted human blood. No leakage of doxorubicin was detected, even when liposomes were circulating for 48 h in human plasma before apheresis. Conclusions: Convenient apheresis techniques are capable of a safe and efficient elimination of therapeutic used liposomal doxorubicin in an experimental model system. J. Clin. Apheresis, 2010. © 2010 Wiley-Liss, Inc. [source] Intertriginous epidermal dysmaturation from pegylated liposomal doxorubicinJOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2003Joseph C. English III Background:, A new formulation of doxorubicin (pegylated liposomal doxorubicin) has been developed to attenuate the systemic side effects produced by this agent. Although pegylated liposomal doxorubicin has a much lower risk for cardiotoxicity, it has been associated with cutaneous side effects that differ from, and may also be more frequent than, those produced by the free form of the drug. Methods:, We report a case of interface dermatitis with keratinocyte dysmaturation, limited to the intertriginous areas, in a patient who received pegylated liposomal doxorubicin, and we review the literature. Results:, It is possible that the enhanced delivery of doxorubicin in liposomal form promotes cutaneous side effects of the drug. We consider the possible mechanisms for keratinocyte dysmaturation produced by this form of doxorubicin. Conclusions:, Our findings further suggest that inflammatory changes seen on biopsy may not always allow a reliable histopathologic distinction between this chemotherapy effect and graft-versus-host disease. [source] Improved therapeutic responses for liposomal doxorubicin targeted via thrombospondin peptidomimetics versus untargeted doxorubicinJOURNAL OF PEPTIDE SCIENCE, Issue 7 2010M. P. Rivera-Fillat Abstract New therapies in cancer treatment are focusing on multifaceted approaches to starve and kill tumors utilizing both antiangiogenic and chemotherapeutic compounds. In this work, we searched for a peptide vector that would home liposomes both to endothelial and tumor cells. [Abu6]TSPB and [Abu6]TSPA, aspartimide analogs of natural sequences of TSP-1 and TSP-2, respectively, were tested for adhesion of tumor and endothelial cells, in vivo and in vitro antiangiogenic effects, and in vivo antitumor action. Both peptides support the adhesion of both types of cells, but only [Abu6]TSPA inhibits the angiogenesis in vivo, and [Abu6]TSPA-targeted L -DOX decreases by 58% (P < 0.008) the HT29 tumor growth in nude mice. The improvement in the doxorubicin antitumor effect should be attributed to the antiangiogenic effect of [Abu6]TSPA, since [Abu6]TSPB, despite being a good ligand for both cell types, had no effect on tumor growth. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. [source] Sequential treatment of angiosarcoma of the back with liposomal doxorubicin and radiotherapyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 6 2005P Santos [source] Symptomatic Pulmonary Allograft Kaposi's Sarcoma in Two Lung Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2008S. J. Sathy Kaposi's sarcoma (KS) is associated with solid-organ transplantation, but is extremely rare after lung transplantation. In this report, we describe two unique cases of lung transplant recipients who developed KS in the lung allograft and were treated with sirolimus and liposomal doxorubicin. One patient survived 12 months after the diagnosis of KS; the other survived 3 months after diagnosis and was found to have concomitant EBV-negative, HHV-8-positive B-cell lymphoma. We demonstrate a partial response of pulmonary KS to reduced immunosuppression and the initiation of sirolimus in one patient, as well as an association between increasing HHV-8 viremia and progression of pulmonary KS. Our report highlights the importance of secondary malignancies in patients with transplant-related KS and supports the association between HHV-8 infection and EBV-negative PTLD. [source] Recurrent ovarian cancer: Treatment with pegylated liposomal doxorubicin; a Westmead Cancer Care Centre experienceASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2010Rachel F DEAR Abstract Aim: To describe the overall survival, progression-free survival, response rate and toxicity of pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer. Methods: A retrospective study of 45 patients with recurrent or progressive ovarian cancer was conducted at the Westmead Cancer Care Centre. Patients received PLD at a starting dose of 30,50 mg/m2 every 4 weeks. Results: A total of 43 patients were included for analysis. The starting dose was 40 mg/m2 in 67% of cases, and 21 % had a dose increase. A median of 2 cycles (mean 3, range 1,7) was given. All patients were assessable for response and 77% stopped treatment due to progressive disease. The overall response rate to PLD assessed by CA-125 criteria was 14 percent (six of 43 patients). Five patients (12 percent) were from the potentially platinum-sensitive group and one (2 percent) was from the platinum-resistant group. The overall median progression-free survival was 52 days (2 months), which was greater in the platinum-sensitive than in the platinum-resistant group (4.4 months vs 1.7 months, respectively, P = 0.030). The median overall survival was 296 days (10.6 months) with a trend for this to be longer in the platinum-sensitive than in the platinum-resistant group (13 vs 9 months, P = 0.393). Overall 25 percent of patients had grade 2 or 3 toxicity. Conclusion: The benefit of PLD in platinum-resistant recurrent ovarian cancer is small and the treatment has considerable toxicity. These data support the need to establish whether chemotherapy in this setting has any favorable effect on quality of life. The Australian New Zealand Gynaecological Oncology Group is currently addressing this question in a large prospective study measuring both the subjective and objective benefit (response and survival) of palliative chemotherapy in platinum-resistant or refractory ovarian cancer in Australia. Clinicians are urged to enter their patients in this study to address this important question. [source] Low to moderate cumulative doses of pegylated liposomal doxorubicin in the treatment of classic Kaposi sarcoma in elderly patients with comorbiditiesBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2008I. Potouridou No abstract is available for this article. [source] Pegylated liposomal doxorubicin in stage IVB mycosis fungoidesBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2005G. Di Lorenzo Summary Background, Previous studies have shown that pegylated liposomal doxorubicin (LD) is effective in the treatment of relapsing or recalcitrant cutaneous T-cell lymphoma. Objectives, To evaluate the activity and toxicity of LD in patients with stage IVB mycosis fungoides (MF). Methods, In this retrospective study, we evaluated outcomes and recorded adverse effects in 10 patients with MF (seven men and three women) with extracutaneous involvement. Patients were treated with LD 20 mg m,2 administered intravenously every 4 weeks. Results, All patients received at least two cycles of LD, three patients received four cycles and one patient received six cycles. Three patients (30%) had a partial response and two patients had stable disease. Grade 1,2 leucopenia occurred in three of the 10 patients, and grade 4 leucopenia in one. Three patients had grade 2 palmoplantar erythrodysaesthesia. Conclusions, This study demonstrates that LD is beneficial in terms of activity and toxicity in stage IVB MF. These observations should be verified in larger studies. [source] Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcomaCANCER, Issue 16 2010Evidence of symptom palliation from chemotherapy Abstract BACKGROUND: Paclitaxel and pegylated liposomal doxorubicin (PLD) are active cytotoxic agents for the treatment of human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). A randomized trial comparing the efficacy and toxicity of paclitaxel and PLD was performed, and the effects of therapy on symptom palliation and quality of life were determined. METHODS: Patients with advanced HIV-associated KS were randomly assigned to receive paclitaxel at a dose of 100 mg/m2 intravenously (iv) every 2 weeks or PLD at a dose of 20 mg/m2 iv every 3 weeks. The KS Functional Assessment of HIV (FAHI) quality of life instrument was used before and after every other treatment cycle. RESULTS: The study included 73 analyzable patients enrolled between 1998 and 2002, including 36 in the paclitaxel arm and 37 in the PLD arm; 73% of patients received highly active antiretroviral therapy (HAART) and 32% had an undetectable viral load (<400 copies/mL). Treatment was associated with significant improvements in pain (P = .024) and swelling (P < .001). Of the 36 patients who reported that pain interfered with their normal work or activities at baseline, 25 (69%) improved. Of the 41 patients who reported swelling at baseline, 38 (93%) improved. Comparing the paclitaxel and PLD arms revealed comparable response rates (56% vs 46%; P = .49), median progression-free survival (17.5 months vs 12.2 months; P = .66), and 2-year survival rates (79% vs 78%; P = .75), but somewhat more grade 3 to 5 toxicity for paclitaxel (84% vs 66%; P = .077). CONCLUSIONS: Treatment with either paclitaxel or PLD appears to produce significant improvements in pain and swelling in patients with advanced, symptomatic, HIV-associated KS treated in the HAART era. Cancer 2010. © 2010 American Cancer Society. [source] Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapyCANCER, Issue 7 2008Pieter Sonneveld MD Abstract BACKGROUND Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma (MM). In the current analysis, they determined 1) the efficacy of PLD plus bortezomib versus bortezomib alone in patients with MM who had failed on prior thalidomide/lenalidomide (immunomodulatory drug [IMiD]) treatment and 2) the efficacy and safety profile of PLD plus bortezomib in IMiD-exposed and IMiD-naive patients. METHODS This prespecified analysis included 646 patients who were randomized to receive either PLD with bortezomib (n = 324; 194 IMiD-naive patients and 130 IMiD-exposed patients) or bortezomib alone (n = 322; 184 IMiD-naive patients and 138 IMiD-exposed patients). The primary efficacy endpoint was TTP, and secondary endpoints included overall survival, response rate, and safety. RESULTS The median TTP was significantly longer with PLD plus bortezomib compared with bortezomib alone in IMiD-exposed patients (270 days vs 205 days). No statistical difference was noted with respect to TTP between IMiD-naive (295 days) versus IMiD-exposed (270 days) subgroups who received PLD plus bortezomib. A sustained trend favoring combination therapy was observed in analyses of overall survival. In patients who achieved a response, the response duration was comparable for IMiD-naive patients and IMiD-exposed patients in the combination treatment group and lasted a median of 310 days and 319 days, respectively. The incidence of grade 3/4 adverse events was similar with PLD plus bortezomib regardless of prior IMiD exposure. CONCLUSIONS A significantly prolonged TTP was observed with combined PLD plus bortezomib combination therapy compared with bortezomib alone despite prior IMiD exposure. For the combination treatment arm in the IMiD-naive and IMiD-exposed subgroups, TTP was comparable. Similarly, the safety profile of the PLD plus bortezomib combination was unaltered by prior IMiD exposure. Cancer 2008. © 2008 American Cancer Society. [source] Pegylated liposomal doxorubicin-efficacy in patients with recurrent high-grade gliomaCANCER, Issue 6 2004Peter Hau M.D. Abstract BACKGROUND Doxorubicin exhibits high efficacy in malignant glioma cell cultures. Nonetheless, as a standard formulation, doxorubicin has not been used clinically, due to poor penetration of the blood-brain barrier. Furthermore, doxorubicin is known to induce tumor resistance genes. To address both of these issues, the authors investigated the use of pegylated liposomal doxorubicin (CaelyxÔ; Essex Pharma, Munich, Germany) alone (Trial 1) and in combination with tamoxifen (Trial 2) in two sequentially performed nonrandomized prospective Phase II trials involving patients with recurrent high-grade glioma. METHODS Twenty patients were included in each trial. Progression-free survival at 6 months (PFS-6) and toxicity were the primary endpoints. Expression of the tumor resistance proteins multidrug resistance protein 1 (MDR-1) and multiple resistance protein (MRP) was evaluated by immunohistochemical methods and by sestamibi,single-photon emission computed tomography (SPECT). RESULTS The overall response rate (including cases of disease stabilization) was 40% in both Trial 1 and Trial 2. PFS-6 was 15%, and the median time to disease progression was 17 weeks. It is noteworthy that 40% of patients with Grade III tumors had long-term responses, which lasted for up to 3 years. There was no significant difference between Trial 1 and Trial 2 in terms of efficacy. Both regimens were well tolerated, with the main side effect being palmoplantar erythrodysesthesia. The authors found no correlation between clinical response and expression of tumor resistance genes or between clinical response and SPECT data. CONCLUSIONS Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma. None of the putative predictors for response that were evaluated proved to be significant in this setting. Cancer 2004. © 2004 American Cancer Society. [source] Enhanced antitumor efficacy of folate-linked liposomal doxorubicin with TGF-, type I receptor inhibitorCANCER SCIENCE, Issue 10 2010Yukimi Taniguchi Tumor cell targeting of drug carriers is a promising strategy and uses the attachment of various ligands to enhance the therapeutic potential of chemotherapy agents. Folic acid is a high-affinity ligand for folate receptor, which is a functional tumor-specific receptor. The transforming growth factor (TGF)-, type I receptor (T,R-I) inhibitor A-83-01 was expected to enhance the accumulation of nanocarriers in tumors by changing the microvascular environment. To enhance the therapeutic effect of folate-linked liposomal doxorubicin (F-SL), we co-administrated F-SL with A-83-01. Intraperitoneally injected A-83-01-induced alterations in the cancer-associated neovasculature were examined by magnetic resonance imaging (MRI) and histological analysis. The targeting efficacy of single intravenous injections of F-SL combined with A-83-01 was evaluated by measurement of the biodistribution and the antitumor effect in mice bearing murine lung carcinoma M109. A-83-01 temporarily changed the tumor vasculature around 3 h post injection. A-83-01 induced 1.7-fold higher drug accumulation of F-SL in the tumor than liposome alone at 24 h post injection. Moreover F-SL co-administrated with A-83-01 showed significantly greater antitumor activity than F-SL alone. This study shows that co-administration of T,R-I inhibitor will open a new strategy for the use of FR-targeting nanocarriers for cancer treatment. (Cancer Sci 2010); 00: 000,000 [source] Antitumor effect of MCC-465, pegylated liposomal doxorubicin tagged with newly developed monoclonal antibody GAH, in colorectal cancer xenograftsCANCER SCIENCE, Issue 7 2004Tetsuya Hamaguchi MCC-465 is an immunoliposome-encapsulated doxorubicin. The liposome is tagged with polyethylene glycol and the F(ab)2 of a monoclonal antibody named GAH, a human antibody obtained by the hybridoma technique. The epitope recognized by GAH is not well characterized, but human gastric, colorectal, and mammary cancer cells were GAH-positive, while the normal counterparts were GAH-negative. Pegylated liposome doxorubicin (PLD) and MCC-465 did not show significant antitumor activity against GAH-negative Caco-2 xenografts. On the other hand, MCC-465 exhibited significantly superior antitumor effects against GAH-positive WiDr-Tc and SW837 xenografts, compared with PLD. Immunohis-tochemistry with GAH revealed that 94% (100 of 106) of surgical specimens of colorectal cancer were GAH-positive. These results warrant a phase I clinical trial of MCC-465 for patients with metastatic colorectal cancer. [source] | ||||||||||||||||||||||