Liposomal Paclitaxel Research Articles

Thalidomide combined with chemo-radiotherapy for treating esophageal cancer: A randomized controlled study.

The aim of the present study was to investigate the efficiency and safety of a combination of thalidomide and chemo-radiotherapy (CRT) for treating esophageal cancer (EC). Eligible patients received two cycles of chemotherapy using paclitaxel liposome and cisplatin concurrently with three-dimensional radiotherapy. Following radiotherapy, two cycles of maintenance chemotherapy were performed. Patients with elevation of vascular endothelial growth factor (VEGF) during radiotherapy were randomly divided into: i) a test group (n=31), who received a combination of CRT and thalidomide; and ii) a control group (n=30), who received CRT only. Patients with locally advanced EC in the test group demonstrated a significantly improved 3-year overall survival (OS) rate, progression-free survival (PFS) rate, local control and median PFS time compared with the control group (P<0.05). Multivariate analysis indicated that Tumor-Node-Metastasis (TNM) stage was associated with the OS time, while TNM stage and the residence of cancer cells following radiotherapy were associated with PFS time. The present data indicate that thalidomide contributes to an improvement of prognosis for patients with locally advanced EC with elevated serum VEGF levels during radiotherapy. In addition, the toxicities induced by thalidomide were demonstrated to be tolerable.

Diagnosis and treatment of Kaposi's sarcoma: European consensus-based interdisciplinary guideline (EDF/EADO/EORTC)

Kaposi's sarcoma (KS) is a multifocal neoplasm of lymphatic endothelium-derived cells infected with human herpesvirus 8. Four clinical subtypes are distinguished: the classic, the endemic, the epidemic subtype in HIV positive patients and the iatrogenic subtype. The diagnosis is primarily based on clinical features and confirmation by histology with immunohistochemistry. Cutaneous distribution and severity, mucosal, nodal and visceral involvement depend on the type of KS with in general indolent behaviour and chronic evolution in the classic subtype and the more severe forms in iatrogenic or epidemic subtypes. Management should aim at achieving disease control. For localised lesions, several local therapies have been developed without randomised trial comparisons. Radiotherapy, intralesional chemotherapies and electrochemotherapy have high response rates. Topical treatments—imiquimod or topical 9-cis-retinoid acid—can also be used. Systemic treatments are reserved for locally aggressive extensive and disseminated KS: the recommended first-line agents are pegylated liposomal doxorubicin (PLD) and paclitaxel. In CKS, PLD or low-dose interferon-alfa are the recommended first-line agents in younger patients. In AIDS-related KS, combination antiretroviral therapy is the first treatment option; specific systemic treatment is needed only in case of extensive disease and in the prevention and treatment of immune reconstitution inflammatory syndrome. In post-transplant KS, tapering down immunosuppressive therapy and switching to mammalian target of rapamycin (m-TOR) inhibitors are used. Follow-up schedules for patients with KS disease depend on aggressiveness of the disease.

Clinical efficacy and safety of paclitaxel liposomes as first-line chemotherapy in advanced gastric cancer.

Aim: To compare the performance of first-line paclitaxel liposome + oxaliplatin and SOX (tegafur/gimeracil/oteracil + oxaliplatin) in advanced gastric cancer patients.Materials& methods:Stage IIb-IV gastric cancer patients underwent either first-line paclitaxel liposome + oxaliplatin (n = 52) or SOX (n = 69) between 2010-2013, and followed up until 2015 or death. Results: Both groups had similar objective response rate (p = 0.48) and disease control rate (p = 0.992) after two chemotherapy cycles, median progression-free survival (p = 0.495) and median overall survival (p = 0.208). Liposome group had significantly lower rate of grade I-II platelet decline and liver function damage (p = 0.04 and 0.019). Multivariate COX regression identified pre-treatment neutrophil-to-lymphocyte ratio as an independent prognostic factor.Conclusion:First-line paclitaxel liposome + oxaliplatin has comparable efficacy, but causes reduced adverse reactions in advanced gastric cancer as compared with SOX.

Short and Long-Term Effects of the Exposure of Breast Cancer Cell Lines to Different Ratios of Free or Co-Encapsulated Liposomal Paclitaxel and Doxorubicin.

Background: Associating paclitaxel (PTX) to doxorubicin (DXR) is one of the main chemotherapy strategies for breast cancer (BC) management. Protocols currently available consist in administering both drugs on their maximum tolerated dose, not taking into account the possible differences in efficacy due to their combination ratio. In the present study, the short and long-term cytotoxic effects as well as migratory effects of PTX, DXR, and its combinations at 10:1; 1:1 and 1:10 PTX:DXR molar ratios either free or co-encapsulated in liposomes were evaluated against three human BC cell lines (MDA-MB-231, MCF-7, and SKBR-3). Method: The MTT assay was used to screen for synergy or antagonism between PTX and DXR and the combination index value was calculated using the CalcuSyn software. Nuclear morphological alterations were evaluated by staining the cells with Hoescht 33342. The investigation of senescence and clonogenicity of BC cell lines exposed to different treatments was also studied. In addition, the ability of these cells to migrate was assessed. Results: Taken together, the results presented herein allow us to suggest that there is no benefit in enhancing the PTX concentration above that of DXR in the combination for any of the three cell lines tested. Conclusion: The developed liposomes co-encapsulating PTX and DXR in different molar ratios retained the biological properties of the mixture of free drugs and are valuable for planning new therapeutic strategies.

Evaluation of clinical effectiveness of paclitaxel and ursolic acid co-loaded liposomes as enhanced treatment for head and neck squamous cell carcinoma

Purpose: To enhance the clinical effectiveness of paclitaxel (PTX) by co-delivery with ursolic acid (UA) for the treatment of head and neck cancer. Methods: Co-loaded liposomes of PTX and UA (UA-PTX-LiP) were prepared by thin-film hydration method. Their size and loading efficiency were determined using dynamic light scattering (DLS) technique and high performance liquid chromatography (HPLC), respectively. The effectiveness of UAPTX-LiP against HSC-3 human head and neck cancer cell-lines was compared with that of PTX liposome (PTX-LiP) using systemic cell-based in vitro evaluation with MTT assay. Fluorescent microscopy was used for cell uptake studies. Results: The size of the prepared UA-PTX-LiP was 126.5 ± 3.22 nm. The ratiometric system for PTX and UA as liposom es revealed significantly enhanced cytotoxicity, with comparatively lower IC 50 , whencompared to individual PTX-Lip. Fluorescent microscopy revealed the internalization ability of UA-PTXLiP by targeted delivery of PTX in HSC-3 human head and neck cancer cell-line. Conclusion: These results show that UA-PTX-LiP successfully enhances the therapeutic potential and clinical outcomes of PTX in head-and-neck cancer, and also demonstrate the useful effect of combination of UA and PTX in chemotherapy. Keywords: Paclitaxel, Ursolic acid, Combination chemotherapy, Head-and-neck squamous cancer

Phase II Study of a Bi-Weekly Chemotherapy Regimen of Combined Liposomal Paclitaxel and Nedaplatin for the Treatment of Advanced Squamous Cell Lung Cancer

The platinum-based, two-drug, 3-week regimen is currently the main first-line chemotherapy program for the treatment of advanced squamous cell lung cancer. The aim of this phase II clinical study was to evaluate the efficacy and adverse events of the bi-weekly program of liposomal paclitaxel combined with nedaplatin as a first-line treatment for advanced squamous cell lung cancer. A total of 52 cases of advanced squamous cell lung cancer were included in this phase II clinical trial. Patients received intravenous infusion of liposomal paclitaxel (100 mg/m2) and nedaplatin (50 mg/m2) on days 1 and 15 of a 4-week cycle. Each patient received two to six cycles of chemotherapy, consistent with the regimen of combined liposomal paclitaxel and nedaplatin. The total effective rate of this chemotherapy program was 37.5%. The median progression-free survival time was 8.5 months (95% confidence interval: 7.8–9.2). The median survival time was 16 months (95% confidence interval: 14.1–17.9). The main adverse event was myelosuppression. Grade 3 leukopenia was noted in seven patients (13.5%), and no grade 4 leukopenia was observed. Grade 3 anemia was noted in four patients (7.7%), and no grade 4 anemia was observed. In addition, no grade 2 or higher thrombocytopenia and no grade 3 or 4 non-bone marrow toxicity was detected. The bi-weekly program of liposomal paclitaxel combined with nedaplatin is effective for the treatment of advanced squamous cell lung cancer, with high safety and few adverse events. However, additional studies are warranted to confirm these results. The trial was registered under the number ChiCTR-OIN-17011423.

Kaposi sarcoma.

Kaposi sarcoma (KS) gained public attention as an AIDS-defining malignancy; itsappearance on the skin was a highly stigmatizing sign of HIV infection during the height of the AIDS epidemic. The widespread introduction of effective antiretrovirals to control HIV by restoring immunocompetence reduced the prevalence of AIDS-related KS, although KS does occur in individuals with well-controlled HIV infection. KS also presents in individuals without HIV infection in older men (classic KS), in sub-Saharan Africa (endemic KS) and in transplant recipients (iatrogenic KS). The aetiologic agent of KS is KS herpesvirus (KSHV; also known as human herpesvirus-8), and viral proteins can induce KS-associated cellular changes that enable the virus to evade the host immune system and allow the infected cell to survive and proliferate despite viral infection. Currently, most cases of KS occur in sub-Saharan Africa, where KSHV infection is prevalent owing to transmission by saliva in childhood compounded by the ongoing AIDS epidemic. Treatment for early AIDS-related KS in previously untreated patients should start with the control of HIV with antiretrovirals, which frequently results in KS regression. In advanced-stage KS, chemotherapy with pegylated liposomal doxorubicin or paclitaxel is the most common treatment, although it is seldom curative. In sub-Saharan Africa, KS continues to have a poor prognosis. Newer treatments for KS based on the mechanisms of its pathogenesis are being explored.

Safety, activity, and molecular heterogeneity following neoadjuvant non-pegylated liposomal doxorubicin, paclitaxel, trastuzumab, and pertuzumab in HER2-positive breast cancer (Opti-HER HEART): an open-label, single-group, multicenter, phase 2 trial

The Opti-HER HEART trial aimed to optimize activity while minimizing cardiac risk by combining trastuzumab, pertuzumab, and paclitaxel with non-pegylated liposomal doxorubicin in the treatment of HER2-positive early breast cancer. Patients with stage II–IIIB HER2-positive breast cancer received neoadjuvant trastuzumab, pertuzumab, paclitaxel, and a non-pegylated liposomal doxorubicin every three weeks for six cycles. The primary endpoint was cardiac safety during neoadjuvant therapy. Type A (symptomatic congestive heart failure) and B (asymptomatic reduction of left ventricular ejection fraction) cardiac events were evaluated. Secondary endpoints included the evaluation of the pathological complete response (pCR) rate and overall response rate, among others. As an ad-hoc exploratory analysis, the expression of 55 breast cancer-related genes, including the PAM50 genes, was measured in 58 baseline tumor samples and 60 surgical specimens. Eighty-three patients were recruited. The incidence of cardiac events during neoadjuvant treatment was 2.4%. No type A cardiac event was observed. The overall pCR rate was 56.6% (95% confidence interval (CI) 45.3–67.5%). The HER2-enriched subtype, which represented 52.0% of all baseline samples, was associated with a higher pCR rate compared to non-HER2-enriched tumors (83.3% vs. 46.3%; odds ratio 5.76, 95% CI 1.71–19.42). The association of subtype with pCR was independent of known clinicopathological variables, including hormone receptor status. Compared to baseline samples, surgical specimens showed a significant downregulation of proliferation-related genes (MKI67 and CCNB1) and ERBB2 levels, and a significant upregulation of luminal-related (ESR1 and PGR) and immune (CD8A) genes. The combination of dual HER2 blockade with trastuzumab and pertuzumab with paclitaxel and non-pegylated liposomal doxorubicin is associated with a low rate of cardiac events. The HER2-enriched subtype is associated with a high rate of pCR. clinicaltrials.gov, NCT01669239 , Registered 20 August 2012.

紫杉醇脂质体与多西他赛联合顺铂治疗晚期肺鳞癌的疗效与安全性对比

紫杉醇脂质体与多西他赛联合顺铂治疗晚期肺鳞癌的疗效与安全性对比

Liposomal paclitaxel versus docetaxel in induction chemotherapy using Taxanes, cisplatin and 5-fluorouracil for locally advanced nasopharyngeal carcinoma

BackgroundWe wished to evaluate the efficacy and safety of liposomal paclitaxel and docetaxel for induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC).MethodsA total of 1498 patients with newly-diagnosed NPC between 2009 and 2017 treated with IC plus concurrent chemotherapy were included in our observational study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and grade-3–4 toxicities were compared between groups using propensity score matching (PSM).ResultsIn total, 767 patients were eligible for this study, with 104 (13.6%) and 663 (86.4%) receiving a liposomal paclitaxel-based and docetaxel-based taxanes, cisplatin and 5-fluorouracil (TPF) regimen, respectively. PSM identified 103 patients in the liposomal-paclitaxel group and 287 patients in the docetaxel group. There was no significant difference at 3 years for OS (92.2% vs. 93.9%, P = 0.942), PFS (82.6% vs. 81.7%, P = 0.394), LRFS (94.7% vs. 93.3%, P = 0.981) or DMFS (84.6% vs. 87.4%, P = 0.371) between the two groups after PSM. Significant interactions were not observed between the effect of chemotherapy regimen and sex, age, T stage, N stage, overall stage, or Epstein–Barr virus DNA level in the subgroup multivariate analysis. The prevalence of grade-3–4 leukopenia and neutropenia in the liposomal-paclitaxel group was significantly lower than that of the docetaxel group (P < 0.05 for all).ConclusionsCompared with docetaxel, liposomal paclitaxel has identical anti-tumor efficacy, but causes fewer and milder adverse reactions in IC for NPC.

Induction Chemotherapy with Paclitaxel Liposome, Nedaplatin, and Fluorouracil in Patients with Locally Advanced Nasopharyngeal Carcinoma: A Phase II Study

A previous study found that adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy could improve failure-free survival in patients with locoregionally advanced nasopharyngeal carcinoma (NCT01245959). Paclitaxel liposome may have fewer side effects and work better than paclitaxel. Nedaplatin, a cisplatin analog, has been developed to decrease the toxicities induced by cisplatin, such as nephrotoxicity and gastrointestinal toxicity. In this study, we aimed to evaluate the safety and efficacy of induction chemotherapy with paclitaxel liposome, nedaplatin, and fluorouracil in patients with locally advanced nasopharyngeal carcinoma. In total we included 46 patients with newly diagnosed and pathologically confirmed stage III-IV nonkeratinized nasopharyngeal carcinoma in Nanjing University affiliated Drum Tower Hospital from 2015 May to 2017 June. Patients were treated with paclitaxel Liposome (135mg/m2), nedaplatin (60mg/m2), and fluorouracil (600mg/m2/day×5days), every 3 weeks for 2 cycles. If patients achieved partial response (PR) or complete response (CR) according to the RECIST criteria 1.0, another cycle was then added. Radiotherapy plus concurrent chemotherapy with nedaplatin was subsequently given with a total dose of 70Gy-74Gy with 2Gy per fraction in 35-37 fractions. Treatment response was evaluated 1 month after the end of the treatment. If patients achieved PR or CR, the treatment was consequently ended. The median age of studied patients was 50 years old (range, 25-74 years). Twenty-eight patients (60.9%, 28/46) had stage III disease, nine (19.6%, 9/46) had stage IVa disease and nine patients (19.6%, 9/46) were with stage IVb disease. Thirty-eight patients completed 3 cycles induction chemotherapy (80.1%, 38/47). CTCAE version 4.0 was referred to grade treatment-related toxicities. Three patients (6.5%, 3/46) developed grade 3 bone marrow suppression. Grade 1 nausea occurred in 3 patients (6.5%, 3/46) and grade 1 malaise occurred in 5 patients (10.9%, 5/46). After the induction chemotherapy, no patients achieved CR, 37 patients (80.4%, 37/46) achieved PR, 8 patients (17.4%, 8/46) were with stable disease (SD) and 2 patients (4.3%, 2/46) developed progressive disease (PD) (PR in primary tumor but with lung metastases). After induction chemotherapy plus concurrent chemoradiotherapy, all the patients achieved PR or CR. The median follow-up was 16 months (range, 8-33 months). Distant metastases occurred in 9 patients (5 patients with lung metastasis, 2 with bone metastasis, 2 with liver metastasis), and only 1 patient had in-field recurrence. Induction chemotherapy with paclitaxel liposome, nedaplatin, and fluorouracil is safe and efficient for patients locally advanced nasopharyngeal carcinoma. This regimen is well tolerated and might be especially helpful for patients with poor performance status. The long-term survival will be updated in future.

Overcoming drug-resistant lung cancer by paclitaxel-loaded hyaluronic acid-coated liposomes targeted to mitochondria

As a major cause for the inefficiency of cancer chemotherapy, multidrug resistance (MDR) has become a major barrier to cancer treatment. Mitochondrion-orientated transportation of smart liposomes has been developed as a promising strategy to deliver anticancer drugs directly to tumor sites and actively target the mitochondria, so that drugs can interfere with mitochondrial function and facilitate cell apoptosis, overcoming MDR. Herein, we report a novel dual-functional paclitaxel (PTX) liposome system possessing both CD44-targeting and mitochondrial-targeting properties to enhance drug accumulation in mitochondria and trigger apoptosis of drug-resistant cancer cells. Mitochondria-targeting PTX-loaded liposomes were prepared by thin-film hydration and then coated with hyaluronic acid (HA) by electrostatic adsorption. We evaluated the characteristics of the PTX liposomes in vitro, and found that their particle size was about 100 nm and increased to ∼140 nm after modification by HA. The entrapment efficiency was larger than 85%, and stability data indicated that the liposomes were physically and chemically stable for at least one week at 4 °C. We further evaluated the intake, mitochondrial targeting, ATP levels, caspase-3 activity measurement, and antitumor actives of the liposomes. The results indicated that HA-coated liposomes with mitochondria targeting had significant inhibitory effects against A549 and A549/Taxol cells, showing them to be a promising means of improving therapeutic efficacy and overcoming MDR in cancer treatment.

P3.01-115 Liposomal Paclitaxel Versus Gemcitabine: Which is Better?

Lung cancer tends to metastasize to lymph nodes in the early stage.The liposomal Paclitaxel(LP) injection has less side effects and higher uptake.It is also characterized as being able to target to organs with rich reticuloendothelial system and keeping a high concentration for a long time. We assume that LP injection has a better curative effect against NSCLC with regional lymph node metastasis. Patients divide to 58 for LP and 56 for Gemcitabine plus cisplatin (GP).Those patients have good comparability in gender,age,ECOG points,pathological pattern,TNM staging and chemotherapy cycles.21 days as a single cycle, each patient finished at least 2 cycles. Estimation was carried on within one week when they have finished the chemotherapy. Chemotherapy Continues if the result turns out CR+PR+SD. surgical treatment would be suggested if the stage of cancer decreases and the lesions of NSCLC turn technically removable. Then continue chemotherapy after surgery, 4 to 6 cycles in total. The alleviation rate of lymph nodes metastasis in LP group is significantly higher.The disease control rate of lymph nodes metastasis is 96.551% vs. 92.857%, p=0.38.The alleviation rate of squamous cell carcinoma and the disease control rate is not statistically significant. The alleviation and disease control rate of primary tumor in LP and GP group does not have statistical significance.And among LA patients,it the same trend. The LP group has a longer period without disease progression and a higher survival rate in 1 year than the GPgroup.The medium PFS of squamous cell carcinoma in 5 LP group is 8 months which is higher than that in GP group (5.5 months) but does not have statistical significance. The survival rate in 1 year of squamous cell is 50% (16/32). The PFS of IIIB stage in LP group is 10 months, significantly higher than GP group(4 months),survival rate in 1 year in LP group is also higher but is not statistically significant. As to side effect, the LP group is significantly lower in the incidence of thrombocytopenia, granulocytopenia, anemia and white blood cell reduction.However, the LP group is higher incidence of alopecia. Chemotherapy with LP has higher alleviation rate than chemotherapy with GP in treating advanced NSCLC with regional lymph node metastasis, especially for squamous cell carcinoma. The survival rate and PFS in stage IIIB/IV of LP is also higher than that of GP. Meanwhile, LP is able to reduce the incidence rate of side effects such as hrombocytopenia, granulocytopenia,anemia, white blood cell reduction, nausea and vomiting.

An open-label, randomized, phase II trial evaluating the efficacy and safety of standard of care with or without bevacizumab in platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer patients previously treated with bevacizumab for front-line or platinum-sensitive ovarian cancer: rationale, design, and methods of the Japanese Gynecologic Oncology Group study JGOG3023

BackgroundWe present the study rationale and design of the JGOG3023 study, an open-label, parallel-arm, randomized, phase II trial that aimed to assess the efficacy and safety of chemotherapy with or without bevacizumab in patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who were previously treated with bevacizumab for front-line or platinum-sensitive ovarian cancer. We hypothesize that patients treated with a combination of single-agent chemotherapy and bevacizumab will show improved progression-free survival (PFS) compared with those treated with single-agent chemotherapy alone, in the setting beyond disease progression following prior bevacizumab treatment.Methods/designA total of 106 patients who have recurrence or progression of ovarian cancer, while receiving chemotherapy or within 6 months after the final dose of platinum, after completing at least three cycles of bevacizumab plus platinum chemotherapy will be randomized in a 1:1 ratio to treatment with single-agent chemotherapy or single-agent chemotherapy combined with bevacizumab. For chemotherapy, one of the following four drugs will be chosen by an investigator: pegylated liposomal doxorubicin, topotecan, paclitaxel, or gemcitabine. The primary endpoint is investigator-assessed PFS. The secondary endpoints are overall survival, objective response rate, number of paracentesis, and response rate by CA125. Safety will be evaluated by the incidence of adverse events.DiscussionThis study will assess the efficacy and safety of bevacizumab in combination with single-agent chemotherapy, which could be used continuously after disease progression following standard platinum-based chemotherapy with bevacizumab.Trial registrationUMIN000017247 (registered April 22, 2015).

Clinical use of trastuzumab combined with different chemotherapy regimens in multi‑line treatment of advanced human epidermal growth factor receptor 2‑positive gastric cancer: A case report

It is generally acknowledged that gastric cancer requires comprehensive treatment approaches to be adopted. For patients with human epidermal growth factor receptor-2 (HER2)-overexpressing gastric cancer, targeting HER2 with trastuzumab in first-line therapy combined with standard chemotherapy significantly improves the prognosis. However, there is a lack of international guidance for second-line treatment if a patient experiences disease progression. There is also no accepted conclusion regarding the efficiency of cross-line therapy with trastuzumab. The present study reports the case of a 55-year-old male with gastric cancer who underwent radical gastrectomy. Immunohistochemistry indicated that samples were EGFR(+) and HER-2(3+), with Ki-67 (20%). From abdominal computed tomography scanning and contrast-enhanced ultrasound following surgery, hepatic metastasis was identified and the patient was administered microwave thermocoagulation therapy. Since December 2012, the patient received multi-line chemotherapy regimens as follows: i) Oxaliplatin, tegafur/gimeracil/oteracil and trastuzumab; ii) paclitaxel liposome and S-1 plus trastuzumab; iii) apatinib; iv) epirubicin/oxaliplatin/xeloda; and v) irinotecan plus trastuzumab. During the course of therapy, the trastuzumab served an important function in multi-line therapy and the patient benefited from the combined therapy. The application of trastuzumab in the multi-line treatment of a patient with HER2-positive advanced gastric cancer may be worthy of investigation for use in the clinic.

Liposils: An effective strategy for stabilizing Paclitaxel loaded liposomes by surface coating with silica

The present work aims at improving stability of paclitaxel (PTX) loaded liposomes by its coating with silica on the surface by a modified sol-gel method. Effect of various components of liposomes such as phosphatidylcholine to cholesterol ratio (PC:CH), PTX and stearylamine on entrapment efficiency (% EE) and particle size were systematically investigated and optimized using central composite design on Design-Expert®. The optimized liposomes were utilized as a template for silica coating to prepare surface coated PTX liposils. Physical stability of liposomes and liposils was evaluated with Triton X-100 and the results indicated that liposils were much more stable as compared to liposomes and the same has been reiterated in stability study performed over 6 months. In vitro cytotoxicity study on B16F10 tumor cells showed cytotoxicity of PTX liposils was not significantly different than PTX liposomes, whereas both were less cytotoxic as compared to the commercial Taxol®. In vivo pharmacokinetics on rats, exhibited increased T1/2 of liposils when compared to liposomes and Taxol®, thus releasing the drug over a longer duration. The enhanced physicochemical stability as well as controlled release of PTX in liposils developed in this study could be an effective alternative to Taxol® and PTX liposomes.

Liposomal paclitaxel induces fewer hematopoietic and cardiovascular complications than bioequivalent doses of Taxol.

Paclitaxel (PTX) exhibits potent antineoplastic activity against various human malignancies; however, clinical application must overcome the inherent hydrophobicity of this molecule. The commercialized Taxol formulation utilizes Cremophor EL (CrEL)/ethanol as a solvent to stabilize and dispense PTX in an aqueous solution. However, adverse CrEL-induced hypersensitivity reactions have been reported in ~30% of recipients, and 40% of patients receiving premedication may also experience this adverse effect. Therefore, the development of a CrEL-free delivery system is crucial, in order to fully exploit the therapeutic efficacy of PTX. In the present study, a novel liposomal PTX (lipo-PTX) formulation was optimized with regards to encapsulation rate and long-term stability, arriving at a molar constituent ratio of soybean phosp hatidylcholine:cholesterol:N-(carbonyl-methoxy-poly-ethylene glycol 2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt:PTX at 95:2:1:2. Comparable doses of lipo-PTX and Taxol were bioequivalent in terms of therapeutic efficacy in xenograft tumor models. However, the systemic side effects, including hematopoietic toxicity, acute hypersensitivity reactions and cardiac irregularities, were significantly reduced in lipo-PTX-treated mice compared with those infused with reference formulations of PTX. In conclusion, the present study reported that lipo-PTX exhibited a higher therapeutic index than clinical PTX formulations.

Induction chemotherapy with paclitaxel liposome, nedaplatin, and fluorouracil in patients with locally advanced nasopharyngeal carcinoma: A phase II study.

e18024Background: A previous study found that adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy could improve failure-free survival in patie...

The anticancer efficacy of paclitaxel liposomes modified with low-toxicity hydrophobic cell-penetrating peptides in breast cancer: an in vitro and in vivo evaluation.

In our recent study, hydrophobic cell-penetrating peptides (CPPs) were demonstrated as an effective method of improving cancer treatment. To provide more evidence and broaden the application range for this promising strategy of improving cancer treatment, novel hydrophobic CPP-modified (PFV-modified) nanoliposomes loaded with paclitaxel, termed PFV-Lip-PTX, were developed as a treatment for breast cancer. Physicochemical evaluations of PFV-Lip-PTX revealed spheroid-like regular vesicles of about 120 nm in diameter with negative charge. An in vitro release study indicated that PTX was released from the liposomes in a controlled and sustained manner. A cellular uptake study indicated that PFV-Lip-PTX exhibited higher internalization efficiency in MCF-7 cells than non-modified liposomes. It was also demonstrated that PFV modification improved the cytotoxicity of PTX via a hydrophobic interaction between the PFV-Lip and cell lipid membranes compared with non-modified liposomes. Moreover, in vivo studies demonstrated that the PFV-modified liposomes led to highly efficient targeting and accumulation in an MCF-7 xenograft tumor and improved the antitumor efficacy of PTX. Finally, PFV-Lip-PTX showed low systemic toxicity evidenced by fewer changes in the body weights of mice and no visible histological changes in major healthy organs. Therefore, our results indicate that PFV-Lip-PTX has great potential in tumor-targeting and effective antitumor treatment.

Case Report of Cardiac Metastasis from Cervical Squamous Carcinoma and its Literature Review

We reported a case of a symptomatic metastasis of squamous cell carcinoma of the uterine cervix (SCCUC) to the right ventricle, then to the right atrium and superior vena cava five years later than the first SCCUC diagnosis. Because of the persistent thrombocytopenia, the treatment was discontinued after only one cycle of reduced paclitaxel liposome five years ago. The patient died six weeks after the diagnosis of cardiac metastasis. We reviewed the literatures in last two decades for the epidemiology, clinical presentaion, diagnosis, treatment and prognosis of SCCUC with cardiac metastasis (SCCUCCM). Dyspnea and chest pain are the common clinical presentations. Echocardiography, cardiac computed tomography (CT) and cardiac magnetic resonance imaging (CMR) are recommended in diagnosis. The prognosis for cardiac metastasis is extremely poor, with a median survival time of 5 months. Thrombocytopenia is a negative factor in the survival time of SCCUC-CM. Aggressive therapy including surgical intervention, chemotherapy, and whole heart radiation therapy may prolong survival time.