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Seminars in Oncology Jun 2007Taxanes are widely used for many solid tumors, including metastatic breast cancer. Enhanced-delivery taxanes (EDTs) were specifically designed to improve the efficacy... (Review)
Review
Taxanes are widely used for many solid tumors, including metastatic breast cancer. Enhanced-delivery taxanes (EDTs) were specifically designed to improve the efficacy and tolerability of taxanes through the utilization of biocompatible, tumor-selective, taxane delivery vehicles, removing the need for drug delivery in toxic, conventional solvents. Nab-paclitaxel is a first-generation EDT that consists of paclitaxel encapsulated in albumin-bound nanoparticles that utilize a standard, endogenous serum albumin pathway to deliver paclitaxel to tumor cells. Second-generation EDTs, including Tocosol Paclitaxel (Sonus Pharmaceuticals, Inc., Bothell, Washington) and paclitaxel poliglumex, use biocompatible drug delivery vehicles that not only eliminate the need for toxic conventional solvents but also exploit tumor pathophysiological phenomena such as enhanced permeability and retention. Emerging evidence suggests that the use of EDTs may promote a more favorable and predictable pharmacokinetic profile with increased bioavailability of taxanes at the tumor site, limiting their exposure to normal tissues and improving the therapeutic benefits associated with taxane treatment.
Topics: Albumins; Animals; Antineoplastic Agents; Drug Carriers; Humans; Mice; Paclitaxel; Polyglutamic Acid; Vitamin E
PubMed: 17598283
DOI: 10.1053/s0093-7754(07)00088-7 -
Clinical Lung Cancer May 2006
PIONEER: a phase III randomized trial of paclitaxel poliglumex versus paclitaxel in chemotherapy-naive women with advanced-stage non-small-cell lung cancer and performance status of 2.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase III as Topic; Female; Humans; Infusions, Intravenous; Lung Neoplasms; Paclitaxel; Patient Selection; Polyglutamic Acid; Randomized Controlled Trials as Topic; Research Design; Women's Health
PubMed: 16800969
DOI: 10.3816/CLC.2006.n.027 -
Cancer Chemotherapy and Pharmacology Apr 2009Determine the toxicity, maximum tolerated dose (MTD), and pharmacokinetics of paclitaxel poliglumex (PPX; CT-2103) in combination with cisplatin administered every 3...
PURPOSE
Determine the toxicity, maximum tolerated dose (MTD), and pharmacokinetics of paclitaxel poliglumex (PPX; CT-2103) in combination with cisplatin administered every 3 weeks.
PATIENTS AND METHODS
Forty-three patients with advanced solid tumors were treated at escalating doses of PPX with a fixed dose of cisplatin at 75 mg/m(2). Conjugated and unconjugated paclitaxel were measured in plasma and urine. Cisplatin, as total platinum content in urine, was also assayed.
RESULTS
Dose-limiting toxicities included neutropenia and neuropathy with a cycle 1 MTD of 210 mg/m(2). Conjugated taxanes had a prolonged half-life of >100 h. Nine patients had partial responses, and 19 had stable disease.
CONCLUSIONS
PPX is a water-soluble paclitaxel-polymer conjugate with a prolonged half-life and a limited volume of distribution. PPX/cisplatin showed good activity in a refractory patient population; however, cumulative neuropathy was a significant issue at high doses, suggesting that a lower dose may be appropriate for prolonged therapy.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cohort Studies; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Neoplasms; Paclitaxel; Polyglutamic Acid; Prognosis; Survival Rate; Treatment Outcome; Young Adult
PubMed: 18682950
DOI: 10.1007/s00280-008-0813-8 -
Gynecologic Oncology Dec 2008To estimate the anti-tumor activity and toxicity of paclitaxel poliglumex (PPX) in patients with persistent or recurrent ovarian, fallopian tube or primary peritoneal...
OBJECTIVES
To estimate the anti-tumor activity and toxicity of paclitaxel poliglumex (PPX) in patients with persistent or recurrent ovarian, fallopian tube or primary peritoneal cancer (EOC) in second or third line treatment.
METHOD
Twenty-five patients received PPX at 235 mg/m(2) every 21 days (Cohort 1). At a planned analysis following first stage accrual, the dose was reduced to 175 mg/m(2) Cohort 2) for additional accrual to 78 patients. RECIST and CTC toxicity criteria were used.
RESULTS
Patients received PPX in the second line (15%) and third line (85%) setting. In cohort 2, 25 out of 47 determined cases (53%) were platinum resistant and 17 out of 43 determined cases (40%) were taxane-resistant. The overall response rates for cohort 2 were 0/49 (0%) CR, 8/49 (16%) PR, and 20/49 (41%) SD. The median progression-free survival (PFS) was 2.8 months (95% CI 1.48-4.8 months) and median overall survival (OS) was 15.4 months. The most frequent grade III or IV toxicities in cohort 2 were: neutropenia (24%/20%), constitutional (8%/0%), gastrointestinal (6%/0%), and neuropathy (24%/0%).
CONCLUSION
PPX at 175 mg/m(2) every 21 days has a modest activity of limited duration when given as second or third line therapy in patients with epithelial ovarian or primary peritoneal cancer. The incidence of neuropathy using this dose in recurrent ovarian cancer is higher than predicted from studies in other tumors with PPX. The Gynecology Oncology Group (GOG) is currently exploring its use at 135 mg/m(2) every 28 days in a randomized trial evaluating maintenance chemotherapy in first remission.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Phytogenic; Cohort Studies; Disease-Free Survival; Dose-Response Relationship, Drug; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Paclitaxel; Peritoneal Neoplasms; Polyglutamic Acid
PubMed: 18829087
DOI: 10.1016/j.ygyno.2008.07.049 -
Clinical Cancer Research : An Official... Nov 2005To determine the safety, maximum tolerated dose, pharmacokinetics, and toxicities associated with administration of paclitaxel poliglumex (PPX, XYOTAX, Cell...
PURPOSE
To determine the safety, maximum tolerated dose, pharmacokinetics, and toxicities associated with administration of paclitaxel poliglumex (PPX, XYOTAX, Cell Therapeutics, Inc., Bresso, Italy) given on either 3-weekly or 2-weekly schedule.
EXPERIMENTAL DESIGN
Nineteen patients were investigated on the 3-weekly phase Ia study and 11 patients on the 2-weekly phase Ib study. Dose escalation starting with 100% increments and one patient per dose level was modulated in accordance with the observed toxicities. Conjugated and unconjugated paclitaxel were measured in plasma.
RESULTS
Dose-limiting toxicity of neutropenia was encountered at 266 mg/m(2) (paclitaxel equivalents) in phase Ia and the maximum tolerated dose was 233 mg/m(2). Neuropathy was dose-limiting in phase Ib with a maximum tolerated dose of 177 mg/m(2). Pharmacokinetic investigations indicated a prolonged half-life of >100 hours for conjugated taxanes. Plasma concentrations of unconjugated paclitaxel were similar to those following administration of an equivalent dose of Taxol. Two partial responses were observed, one in a patient with mesothelioma at 177 mg/m(2) in phase Ia and one in a patient with gastric carcinoma at 175 mg/m(2) in phase Ib.
CONCLUSION
PPX is a water-soluble paclitaxel-polymer conjugate with a prolonged half-life and limited volume of distribution. Dose-limiting toxicities were neutropenia and neuropathy. PPX showed activity in this patient population.
Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Area Under Curve; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Models, Chemical; Neoplasms; Paclitaxel; Polyglutamic Acid; Polymers; Time Factors
PubMed: 16278406
DOI: 10.1158/1078-0432.CCR-05-0803 -
Journal of Thoracic Oncology : Official... Jul 2008Patients with advanced non-small cell lung cancer (NSCLC) and impaired performance status (PS >or= 2) have limited life expectancies and decreased tolerance for... (Comparative Study)
Comparative Study Randomized Controlled Trial
Randomized phase III trial comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with single-agent gemcitabine or vinorelbine for the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer.
BACKGROUND
Patients with advanced non-small cell lung cancer (NSCLC) and impaired performance status (PS >or= 2) have limited life expectancies and decreased tolerance for drug-induced toxicities. Current treatment guidelines indicate that PS 2 patients benefit from systemic therapy. Further refinement of treatment in these patients requires reduction of treatment-associated toxicities while maintaining or improving efficacy. Paclitaxel poliglumex (PPX), a macromolecular polymer-drug conjugate of paclitaxel and poly-l-glutamic acid, may enhance the therapeutic index of paclitaxel.
METHODS
Chemotherapy-naive PS 2 patients with advanced NSCLC randomly received single-agent PPX (175 mg/m) or a comparator (single-agent vinorelbine or gemcitabine). The primary end point of this study was overall survival.
RESULTS
Overall survival was similar between treatment arms (hazard ratio [HR] = 0.95; log-rank p = 0.686). Median and 1-year survival were 7.3 months and 26%, respectively, for PPX versus 6.6 months and 26% for the control arm. There was a nonsignificant trend toward improved survival in women in the PPX arm compared with standard single agents (HR = 0.65; p = 0.069). The most frequent grade 3/4 adverse events in the treatment versus control arm were dyspnea (13% versus 17%, respectively) and fatigue (10% versus 9%). Grade 3/4 neutropenia and anemia were reduced in the PPX arm (2% versus 8% and 3% versus 9%, respectively). Neuropathy, a taxane-specific toxicity, was more common in the PPX arm; grade 3 neuropathy was limited to 3%.
CONCLUSIONS
Single-agent PPX, dosed at 175 mg/m, is active and well tolerated in PS 2 patients with advanced NSCLC. Patients on PPX required fewer red blood cell transfusions, hematopoietic growth factors, opioid analgesics, and clinic visits than patients receiving gemcitabine or vinorelbine.
Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Female; Humans; Lung Neoplasms; Male; Middle Aged; Paclitaxel; Polyglutamic Acid; Survival Rate; Gemcitabine
PubMed: 18594318
DOI: 10.1097/JTO.0b013e31817c6b68 -
Methods and Findings in Experimental... 2010A-3309, Abobotulinumtoxin A, Adalimumab, AIDSVAX gp120 B/E, ALVAC E120TMG, Atorvastatin calcium; Bepridil, Bevacizumab; Candesartan cilexetil, Capecitabine, Cetuximab,...
A-3309, Abobotulinumtoxin A, Adalimumab, AIDSVAX gp120 B/E, ALVAC E120TMG, Atorvastatin calcium; Bepridil, Bevacizumab; Candesartan cilexetil, Capecitabine, Cetuximab, Clopidogrel; Dapagliflozin, Dasatinib, Denosumab, Dexmedetomidine hydrochloride, Diacetylmorphine, Diannexin, Docetaxel, Dutasteride; Entecavir, Eplerenone, Erlotinib hydrochloride, Escitalopram oxalate, Everolimus, Ezetimibe; Fesoterodine fumarate, Flagellin.HuM2e, Fluzone; Glimepiride/rosiglitazone maleate; Hyaluronic acid-paclitaxel bioconjugate; IDX-184, Imatinib mesylate, Infliximab, Insulin glargine, Irbesartan; JX-594; Landiolol, Latrunculin B, Levocetirizine dihydrochloride, Liraglutide, Lyprinol; Metformin, Metronidazole/tetracycline hydrochloride/bismuth biskalcitrate, Mipomersen sodium, Mycophenolic acid sodium salt; Nalfurafine hydrochloride, Nilotinib hydrochloride monohydrate; Paclitaxel nanoparticles, Paclitaxel poliglumex, Peginterferon alfa-2a, Peginterferon alfa-2b, Perospirone hydrochloride, Pimavanserin tartrate, Pirfenidone, Pitavastatin calcium, Prasterone, Prasugrel, Pregabalin, Ranelic acid distrontium salt, Ranibizumab, Remimazolam, Risedronate, Rosuvastatin calcium; Silodosin, Silybin phosphatidylcholine complex, Sirolimus-eluting stent, Sitagliptin phosphate monohydrate, Sorafenib, Sunitinib malate; Tadalafil, Tamsulosin hydrochloride, Technosphere/insulin, Telmisartan, Temsirolimus, Teriparatide, Thymalfasin, Ticagrelor, Toltedorine-XR, Tramadol-XR, Triphosadenine, Trospium-XR; Val8-GLP-1(7-37)OH, Valsartan, Vardenafil hydrochloride hydrate, Varenicline tartrate, Velaglucerase alfa; Zoledronic acid monohydrate.
Topics: Clinical Trials as Topic; Humans
PubMed: 20852754
DOI: 10.1358/mf.2010.32.6.1538165 -
Clinical Lung Cancer Jul 2005
Randomized Controlled Trial
Paclitaxel poliglumex/carboplatin is similar to paclitaxel/carboplatin as first-line treatment in elderly patients with advanced non-small-cell lung cancer and a poor performance status.
Topics: Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Female; Humans; Infusions, Intravenous; Lung Neoplasms; Male; Paclitaxel; Polyglutamic Acid; Treatment Outcome
PubMed: 16098240
DOI: 10.1016/S1525-7304(11)70386-2 -
Anti-cancer Agents in Medicinal... 2019Cancer is a disease characterized by uncontrolled cell growth and proliferation. It has become a major health problem in the past decades and is now the second leading... (Review)
Review
BACKGROUND
Cancer is a disease characterized by uncontrolled cell growth and proliferation. It has become a major health problem in the past decades and is now the second leading cause of death globally. Although, there are different types of treatment such as chemotherapy, immune therapy, radiation, hormone therapy and targeted therapy used against cancer, they have possible side effects and significant deficiencies.
METHODS
This review aims to outline the benefits of medicinal plants and plant-derived products and highlight why they should be used as novel anti-cancer therapeutics. Electronic databases, including PubMed, Scopus, ScienceDirect, Cochrane library, and MedlinePlus were searched to summarize , and clinical studies on anticancer effects of medicinal plants and their bioactive compounds up-to-date.
RESULTS
In recent years, a number of medicinal plants have been administered to cancer patients in order to prevent and treat cancer as an alternative therapy. These plants were used because of their rich anticarcinogenic and chemoprotective potentials. In addition to these remarkable properties, these plants have less toxic anticancer, anti-tumor and anti-proliferation agents than traditional therapeutics. Nevertheless, only a small number of natural anti-tumor products including vinblastine, vincristine, podophyllotoxin, paclitaxel (Taxol) and camptothecin have been tested clinically, while vinflunine ditartrate, anhydrovinblastine, NK-611, tafluposide, paclitaxel poliglumex, combretastatins, salvicine, curcumin, indirubin, triptolide, homoharringtonine are still on trial.
CONCLUSION
Consequently, more effective anticancer compounds are identified during the clinical trials; these natural products could be a key source of antitumor agents in modern anticancer therapy. It is expected that novel anticancer phytopharmaceuticals produced from medicinal plants could be effectively used in prevention and therapy for the cancers.
Topics: Animals; Antineoplastic Agents, Phytogenic; Biological Products; Humans; Molecular Structure; Neoplasms; Plants, Medicinal
PubMed: 30582485
DOI: 10.2174/1871520619666181224121004 -
Annals of Oncology : Official Journal... Mar 2012Despite current trend of targeted therapy development, cytotoxic agents are a mainstay of treatment of patients with breast cancer. We reviewed recent advances in... (Review)
Review
BACKGROUND
Despite current trend of targeted therapy development, cytotoxic agents are a mainstay of treatment of patients with breast cancer. We reviewed recent advances in cytotoxic therapy for patients with metastatic breast cancer (MBC).
MATERIALS AND METHODS
Medline searches were conducted for English language studies using the term 'MBC' and 'cytotoxic drugs'. The data search was restricted to the period 2000-2011.
RESULTS
Several novel cytotoxic compounds, all microtubule inhibitors, have been approved for clinical use in MBC: (i) nab-paclitaxel, reported to improve tumour response and decrease hypersensitivity reactions in comparison with other taxanes; (ii) ixabepilone, shown to have clinical benefit in taxane- and anthracycline-resistant disease and (iii) eribulin, shown to improve overall survival in heavily pre-treated patients, when compared with best available standard treatment. Agents, such as larotaxel, vinflunine, trabectidin and formulations, including cationic liposomal paclitaxel or paclitaxel poliglumex, are currently under evaluation in phase II/III trials.
CONCLUSION
Toxicity and chemotherapy resistance are still major limitations in the treatment of patients with MBC. Further research into new cytotoxic compounds is needed in order to maximise benefit, whilst minimising toxicity.
Topics: Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Cytotoxins; Female; Humans
PubMed: 21896541
DOI: 10.1093/annonc/mdr382