An uncontrolled phase II study evaluating anti-tumor efficacy and safety of ortataxel (BAY 59–8862) in patients with taxane-resistant non-small cell lung cancer

Gurtler, Jayne; Pawel, Joachim von; Spiridonidis, C. Harris; Grossi, Francesco; Larriba, José Luis González; Moscovici, M.; Markovitz, E.; Voliotis, D.; Gottfried, Maya

doi:10.1200/jco.2004.22.90140.7136

Cited by 3 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Available results indicate that ortataxel induces relevant disease stabilization in metastatic taxaneresistant breast cancer and NSCLC, although with poor objective response (Table IV). 166,167 Other novel taxanes, tesetaxel (DJ-927) and milataxel (MAC-321), both poor substrates for P-gp and orally bioavailable, have demonstrated superior antitumor activity compared to docetaxel in in vitro and in vivo MDR-expressing and taxane-resistant tumors. 168,169 Although tesetaxel has relevant antitumor activity against P-gp expressing human cancer cell lines and xenografts, 169 when the drug was administered to taxane-pretreated patients low efficacy was observed 170 (Table IV).…”

Section: Overcoming Tumor Multidrug Resistance K 13mentioning

confidence: 99%

Overcoming tumor multidrug resistance using drugs able to evade P‐glycoprotein or to exploit its expression

Nobili

Landini

Mazzei

et al. 2011

Medicinal Research Reviews

148

View full text Add to dashboard Cite

Multidrug resistance (MDR) is a major obstacle to the effective treatment of cancer. Cellular overproduction of P-glycoprotein (P-gp), which acts as an efflux pump for various anticancer drugs (e.g. anthracyclines, Vinca alkaloids, taxanes, epipodophyllotoxins, and some of the newer antitumor drugs) is one of the more relevant mechanisms underlying MDR. P-gp belongs to the superfamily of ATP-binding cassette transporters and is encoded by the ABCB1 gene. Its overexpression in cancer cells has become a therapeutic target for circumventing MDR. As an alternative to the classical pharmacological strategy of the coadministration of pump inhibitors and cytotoxic substrates of P-gp and to other approaches applied in experimental tumor models (e.g. P-gp-targeting antibodies, ABCB1 gene silencing strategies, and transcriptional modulators) and in the clinical setting (e.g. incapsulation of P-gp substrate anticancer drugs into liposomes or nanoparticles), a more intriguing strategy for circumventing MDR is represented by the development of new anticancer drugs which are not substrates of P-gp (e.g. epothilones, second- and third-generation taxanes and other microtubule modulators, topoisomerase inhibitors). Some of these drugs have already been tested in clinical trials and, in most of cases, show relevant activity in patients previously treated with anticancer agents which are substrates of P-gp. Of these drugs, ixabepilone, an epothilone, was approved in the United States for the treatment of breast cancer patients pretreated with an anthracycline and a taxane. Another innovative approach is the use of molecules whose activity takes advantage of the overexpression of P-gp. The possibility of overcoming MDR using the latter two approaches is reviewed herein.

show abstract

Section: Overcoming Tumor Multidrug Resistance K 13mentioning

confidence: 99%

Overcoming tumor multidrug resistance using drugs able to evade P‐glycoprotein or to exploit its expression

Nobili

Landini

Mazzei

et al. 2011

Medicinal Research Reviews

148

View full text Add to dashboard Cite

show abstract

Resistance To Taxanes

Greenberger

Sampath

Cancer Drug Discovery and Development

View full text Add to dashboard Cite

Resistance to two taxanes, paclitaxel and docetaxel, is frequently observed in cancer patients and limits successful therapy. In experimental systems, resistance to paclitaxel and docetaxel are mediated by alterations in tubulin (the primary site of action of taxanes), proteins that interact with microtubules, energy-dependent efflux pumps, apoptotic proteins, and signal transduction pathways. Clinical correlations with some of these alterations exist, but have not been fully elucidated. Strategies to overcome or circumvent resistance to paclitaxel or docetaxel include inhibition of efflux pumps (which have largely proven to be unsuccessful), the use of novel taxanes or other chemically distinct classes of polymerizing agents that do not interact with drug efflux pumps (currently in clinical trials), and regulation of apoptotic or signal transduction pathways that would restore sensitivity to taxanes. Understanding the basis of resistance at the clinical level is likely to be difficult and complex, but holds the promise of providing a therapeutic opportunity specific to taxane-resistant cancer cells.

show abstract

Novel formulations of taxanes: a review. Old wine in a new bottle?

2006

View full text Add to dashboard Cite

Over the past two decades, the taxanes have played a significant role in the treatment of various malignancies. However, the poor solubility of these compounds necessitates the inclusion of surfactant vehicles in their commercial formulations. Cremophor EL and polysorbate 80 have long comprised the standard solvent system for paclitaxel and docetaxel, respectively. A number of pharmacologic and biologic effects related to both of these drug formulations have been described, including clinically relevant acute hypersensitivity reactions and peripheral neuropathy. In addition, these solvents affect the disposition of intravenously administered solubilized drugs and leach plasticizers from polyvinylchloride infusion sets. A number of strategies to develop formulations of surfactant-free taxanes have been developed. They include albumin nanoparticles, polyglutamates, taxane analogs and prodrugs, emulsions, and lipsomes. An overview of these novel formulations of taxanes, their mechanisms of action, pharmacokinetics, dose and administration, adverse effects, and clinical efficacy will be discussed.

show abstract

An uncontrolled phase II study evaluating anti-tumor efficacy and safety of ortataxel (BAY 59–8862) in patients with taxane-resistant non-small cell lung cancer

Cited by 3 publications

References 0 publications

Overcoming tumor multidrug resistance using drugs able to evade P‐glycoprotein or to exploit its expression

Overcoming tumor multidrug resistance using drugs able to evade P‐glycoprotein or to exploit its expression

Resistance To Taxanes

Novel formulations of taxanes: a review. Old wine in a new bottle?

Contact Info

Product

Resources

About