Patients with solid tumors are at greatest risk for dying from their cancers in the five years following diagnosis. For most malignancies, deaths from other chronic diseases begin to exceed those from cancer at some point. As little is known about the causes of death among long-term survivors of ovarian cancer, we examined causes of death by years from diagnosis.The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with ovarian cancer between 1988 and 2012. We compared causes of death by stage, age, and interval time after diagnosis.A total of 67,385 women were identified. For stage I neoplasms, 13.6% (CI, 13.0-14.2%) died from ovarian cancer, 4.2% (CI, 3.8-4.5%) from cardiovascular disease, 3.6% (CI, 3.3-3.9%) from other causes and 2.6% (CI, 2.4-2.9%) from other tumors; ovarian cancer was the leading cause of death until 7 years after diagnosis after which time deaths are more frequently due to other causes. For those with stage III-IV tumors, 67.8% (CI, 67.3-68.2%) died from ovarian cancer, 2.8% (CI, 2.6-2.9%) from other causes, 2.3% (CI, 2.2-2.4%) from cardiovascular disease and 1.9% (CI, 1.7-2.0%) from other cancers; ovarian cancer was the most frequent cause of death in years 1-15 after which time deaths were more commonly due to other causes.The probability of dying from ovarian cancer decreases with time. Ovarian cancer remains the most common cause of death for 15 years after diagnosis in women with stage III-IV tumors.Copyright © 2015 Elsevier Inc. All rights reserved.

Paclitaxel (PTX) is one of the most effective broad-spectrum chemotherapeutic agents in the treatment of cancers. However, its clinical application has been limited due to its poor water solubility. Its current clinical administration uses the adjuvant of serious side effects and has undesired pharmacokinetics and biodistribution. There is, thus, a need for the development of alternate drug delivery systems of PTX to enhance its solubility, permeability and stability and further to promote a sustained, controlled and targeted delivery that will increase its therapeutic effects and reduce its side effects.This review is focused on recent developments of the various PTX delivery systems such as prodrugs, micelles, liposomes, solid lipid nanoparticles, nanoparticles of biodegradable polymers, dendrimers, nanohydrogels, as well as PTX-eluting stents.Pharmaceutical nanotechnology can provide solutions to solve the problems encountered in drug formulation and drug delivery and may change the way drugs are made. The various nanocarriers could have high efficiency in drug encapsulation and cellular uptake, escape from elimination by microphages due to their appropriate size and surface modification and realize with ligand conjugation-targeted delivery.

Abraxane (ABI-007) is a 130-nm albumin-bound (nab) particle formulation of paclitaxel, devoid of any additional excipients. We hypothesized that this change in formulation alters the systemic disposition of paclitaxel compared with conventional solvent-based formulations (sb-paclitaxel; Taxol), and leads to improved tolerability of the drug.Patients with malignant solid tumors were randomized to receive the recommended single-agent dose of nab-paclitaxel (260 mg/m(2) as a 30-minute infusion) or sb-paclitaxel (175 mg/m(2) as a 3-hour infusion). After cycle 1, patients crossed over to the alternate treatment. Pharmacokinetic studies were carried out for the first cycle of sb-paclitaxel and the first two cycles of nab-paclitaxel.Seventeen patients were treated, with 14 receiving at least one cycle each of nab-paclitaxel and sb-paclitaxel. No change in nab-paclitaxel pharmacokinetics was found between the first and second cycles (P = 0.95), suggesting limited intrasubject variability. Total drug exposure was comparable between the two formulations (P = 0.55) despite the dose difference. However, exposure to unbound paclitaxel was significantly higher after nab-paclitaxel administration, due to the increased free fraction (0.063 +/- 0.021 versus 0.024 +/- 0.009; P < 0.001).This study shows that paclitaxel disposition is subject to considerable variability depending on the formulation used. Because systemic exposure to unbound paclitaxel is likely a driving force behind tumoral uptake, these findings explain, at least in part, previous observations that the administration of nab-paclitaxel is associated with augmented antitumor efficacy compared with solvent-based paclitaxel.

Systemic treatment of metastatic melanoma has been revolutionized by the advent of checkpoint inhibitors and targeted agents which are widely accepted as standard front-line therapies. However, despite these major advances, a substantial portion of patients still fail checkpoint inhibitors and/or targeted agents and are not candidates for clinical trials. Commonly used cytotoxics in these patients include paclitaxel, dacarbazine, platins, and temozolomide. The overall response rates of these agents are usually disappointing and short-lived. Areas covered: Herein, the author provides a literature review of the role of nab-paclitaxel in metastatic melanoma including coverage of its pharmacokinetics, pharmacodynamics and efficacy. Expert opinion: The role of chemotherapy in the treatment of metastatic melanoma is limited to patients who failed checkpoint inhibitors and, when applicable, targeted agents, and those not appropriate for clinical trials. nab-Paclitaxel has single agent activity in chemotherapy-naïve untreated metastatic melanoma which compares favorably to the activity of weekly paclitaxel or single agent dacarbazine. However, the activity in chemotherapy-pretreated patients is modest. Data on nab-paclitaxel in patients pretreated with targeted agents or check point inhibitors are lacking. Further advances are expected from new checkpoint inhibitors and targeted agents for the treatment of metastatic melanoma in addition to the optimal combination and sequencing of these agents.

For almost 15 years there has been stagnation in the systemic treatment of patients with pancreatic ductal adenocarcinoma (PDAC). Recently, several developments seem to indicate clinically relevant improvements in the treatment of patients with metastatic disease. One of these developments is the introduction of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) into the firstline treatment of metastatic disease. In this review, underlying preclinical and clinical data are discussed, with a special focus on mechanisms of action, the potential interaction with albumin and calcium-binding matricellular glycoproteins, such as the secreted protein acidic and rich in cysteine (SPARC), as well as the clinical outcome associated with the use of nab-paclitaxel.

One of the major challenges related to solvent-based taxanes administration in clinical practice is the high rate of hypersensitivity reactions (HSRs). Nab-paclitaxel is a solvent-free, albumin-bound, paclitaxel, which minimize the risk of HSR occurrence. In this single-institution, retrospective analysis, we evaluated stage IIIc-IV epithelial ovarian cancer (EOC) patients, treated with first-line carboplatin/nab-paclitaxel (± bevacizumab), after the occurrence of an HSR with solvent-based paclitaxel (and/or docetaxel). Between April 2012 and December 2018, ten patients (20.8%) received carboplatin/nab-paclitaxel (± bevacizumab) after the occurrence of an HSR to solvent-based taxanes. Among the evaluable patients, ORR was 100%. At median follow-up of 28.5 months, median PFS was 16.7 months, and median OS was 65.4 months, respectively. Median received dose intensity (DI) was 86% and 80% of the projected DI for nab-paclitaxel and carboplatin, respectively. There were no treatment-related grade 4 adverse events. Most relevant treatment-related grade 3 adverse events were: asthenia (10%), hypertransaminasemia (10%), neutropenia (20%), thrombocytopenia (20%), and anemia (10%). No HSR recurrence was observed. The high rate of HSR occurrence could limit first-line treatment options in clinical practice. Carboplatin/nab-paclitaxel association could represent a valid treatment option in this setting.

Single-agent carboplatin is often proposed instead of a conventional carboplatin-paclitaxel doublet in vulnerable older patients with ovarian cancer. Such an approach could have a detrimental effect on outcomes for these patients.To compare the feasibility, efficacy, and safety of single-agent carboplatin every 3 weeks, weekly carboplatin-paclitaxel, or conventional every-3-weeks carboplatin-paclitaxel in vulnerable older patients with ovarian cancer.This international, open-label, 3-arm randomized clinical trial screened 447 women 70 years and older with newly diagnosed stage III/IV ovarian cancer by determining their Geriatric Vulnerability Score; 120 patients with a Geriatric Vulnerability Score of 3 or higher were stratified by country and surgical outcome. Enrollment took place at 48 academic centers in France, Italy, Finland, Denmark, Sweden, and Canada from December 11, 2013, to April 26, 2017. Final analysis database lock April 2019. Data analysis was performed from January 2 to May 2, 2019.Patients were randomized to receive 6 cycles of (1) carboplatin, area under the curve (AUC) 5 mg/mL·min, plus paclitaxel, 175 mg/m2, every 3 weeks; (2) single-agent carboplatin, AUC 5 mg/mL·min or AUC 6 mg/mL·min, every 3 weeks; (3) or weekly carboplatin, AUC 2 mg/mL·min, plus paclitaxel, 60 mg/m2, on days 1, 8, and 15 every 4 weeks.The primary outcome was treatment feasibility, defined as the ability to complete 6 chemotherapy cycles without disease progression, premature toxic effects-related treatment discontinuation, or death.A total of 120 women were randomized. The mean and median age was 80 (interquartile range, 76-83; range, 70-94) years; 43 (36%) had a Geriatric Vulnerability Score of 4 and 13 (11%) had a Geriatric Vulnerability Score of 5; 40 (33%) had stage IV disease. During its third meeting, the independent data monitoring committee's recommendation led to the termination of the trial because single-agent carboplatin was associated with significantly worse survival. Six cycles were completed in 26 of 40 (65%), 19 of 40 (48%), and 24 of 40 (60%) patients in the every-3-weeks combination, single-agent carboplatin, and weekly combination groups, respectively. Treatment-related adverse events were less common with the standard every-3-weeks combination (17 of 40 [43%]) than single-agent carboplatin or weekly combination therapy (both 23 of 40 [58%]). Treatment-related deaths occurred in 4 patients (2 of 40 [5%] in each combination group).This randomized clinical trial shows that compared with every-3-weeks or weekly carboplatin-paclitaxel regimens, single-agent carboplatin was less active with significantly worse survival outcomes in vulnerable older patients with ovarian cancer.ClinicalTrials.gov Identifier: NCT02001272.

Nab-paclitaxel is a novel Cremophor®-free nanoparticle of albumin-stabilized paclitaxel, which has favorable efficacy and toxicity characteristics relative to other solvent-based taxanes, such as paclitaxel and docetaxel.Eligible patients had platinum- and taxane-resistant ovarian cancer, defined by persistent or progressive disease following primary chemotherapy (n = 5) or recurrence within 6 months of treatment completion (n = 42). All patients had measurable disease, no prior therapy for recurrent disease and Gynecologic Oncology Group performance status of ≤ 2. Treatment was nab-paclitaxel, 100 mg/m² days 1, 8, and 15 on a 28-day schedule. The primary endpoint was Response Evaluation Criteria in Solid Tumors v1.0 response rate, evaluated in a 2-stage design (with power of 0.90 for a RR of 25% and with alpha of 0.05 for RR of 10%).Fifty-one patients were enrolled of which 47 were evaluable; median time from frontline therapy completion to registration was 21 days. Patient demographics include median age: 59 (34-78) years, serous histology: 72%, and high-grade: 81%.one complete and 10 partial responses were confirmed (23%); 17 patients (36%) had stable disease. The median progression-free survival was 4.5 months (95% CI: 2.2-6.7); overall survival was 17.4 months (95% CI: 13.2-20.8). Seventeen patients (36%) had PFS > 6 months.there were no grade 4 events; grade 3 events were neutropenia (6), anemia (3), GI (2), metabolic (2), pain (2), and leukopenia (1); neurosensory toxicity was observed as grade 2:5, grade 3:1.Nab-paclitaxel has noteworthy single-agent activity and is tolerable in this cohort of refractory ovarian cancer patients previously treated with paclitaxel.Copyright © 2011 Elsevier Inc. All rights reserved.

晚期上皮性卵巢癌的初始治疗模式为肿瘤细胞减灭术+铂类为基础的联合化疗+一线维持治疗。文章主要阐述了初诊上皮性卵巢癌一线化疗方案的演变和规范应用。紫杉醇联合卡铂3周疗方案仍然是初治上皮性卵巢癌的一线首选化疗方案，其卓越地位无法撼动。同时，文章还回顾了初始化疗中使用贝伐珠单抗的指征，以及其他一线化疗方案的选择指征。最后，文章指出了临床实践中上皮性卵巢癌化疗不规范的问题，强调应重视化疗的规范性，以助于提高我国晚期上皮性卵巢癌患者的生存率。

Taxane induced neuropathy (TIN) is the most limiting side effect of taxane based chemotherapy, relative to the majority of breast cancer patients undergoing therapy with both docetaxel and paclitaxel. The symptoms begin symmetrically from the toes, because the tips of the longest nerves are affected for first. The patients report sensory symptoms such as paresthesia, dysesthesia, numbness, electric shock-like sensation, motor impairment and neuropathic pain. There is a great inter-individual variability among breast cancer women treated with taxanes, in fact 20-30% of them don't develop neurotoxicity. Actually, there is no standard therapy for TIN, although many medications, antioxidants and natural substances have been tested in vitro and in vivo. We will summarize all most recent literature data on TIN prevention and treatment, in order to reach an improvement in TIN management. Further studies are needed to evaluate new therapies that restore neuronal function and improve life quality of patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.