larotaxel and Breast-Neoplasms

Breast cancer is the most common malignant disease in women all over the world and its chemotherapy outcome is restricted by multidrug resistance. Here, a nanostructure by functional larotaxel liposomes decorated with guanine-rich quadruplex nucleotide-lipid derivative for treatment of resistant breast cancer is developed. The studies are performed on the resistant breast cancer cells and the cancer-bearing mice. The nucleotide-lipid derivative (DSPE-PEG

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Female; Guanine; Guanine Nucleotides; Humans; Liposomes; Mice; Nanostructures; Taxoids

The treatment of recurrent, progressing, metastatic breast cancer, which has previously been exposed to anthracyclines and/or taxanes is not only a major clinical challenge, but has a significant social impact too. In the absence of formal guidelines, this review has aimed to summarize the published evidence that is needed to guide clinical decision-making. Four new agents are approved for use in this setting: capecitabine, gemcitabine, ixabepilone, and nanoparticle albumin-bound paclitaxel. Nevertheless this review summarizes the results of studies with other active agents, as liposomal doxorubicin, rotation of taxanes, larotaxel, vinorelbine, and other biological agents.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Capecitabine; Deoxycytidine; Disease Progression; Doxorubicin; Epothilones; Female; Fluorouracil; Gemcitabine; Humans; Paclitaxel; Salvage Therapy; Taxoids; Vinblastine; Vinorelbine

Treatment options are limited for patients with refractory metastatic breast cancer (MBC). Larotaxel (XRP9881) is a novel taxoid with preclinical activity against taxane-resistant breast cancer. The current phase II trial of larotaxel was conducted in women with taxane-treated MBC.. Patients were stratified by response to prior taxane therapy (resistant or nonresistant). Larotaxel 90 mg/m(2) was administered as a 1-h infusion every 3 weeks. Patients were evaluated for tumor response every two cycles. A blinded external response review committee determined the overall response rate (ORR), duration of response (DOR), and time to progression (TtP) of the disease. Median survival time (MST) and safety were also evaluated.. One hundred and thirty patients were treated. In the nonresistant group, the ORR was 42%; median DOR 5.3 months; median TtP 5.4 months; and MST 22.6 months. In the resistant group, the ORR was 19%; median DOR 5.0 months; median TtP 1.6 months; and MST 9.8 months. The most common grade 3/4 adverse events were neutropenia (82%), fatigue (15%), diarrhea (12%), febrile neutropenia (9%), neutropenic infection (8%), and sensory neuropathy (7%).. Larotaxel has good activity, manageable toxicity, and a favorable therapeutic index in women with taxane-pretreated MBC.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Cohort Studies; Diarrhea; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Fatigue; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Middle Aged; Neoplasm Metastasis; Neutropenia; Prospective Studies; Taxoids; Time Factors; Treatment Outcome

Two epimeric metabolites of Larotaxel were synthesized in eight steps from 10-DAB III as a commercial material and their structures were characterized using NMR and MS spectral data. The cytotoxicity of two metabolites was performed on breast cancer cell lines MCF-7, MX-1 and MDA-MB-231. It is remarkable that both of these two desired taxanes showed great potent cytotoxic effect.

Topics: Breast Neoplasms; Cell Line, Tumor; Humans; Proton Magnetic Resonance Spectroscopy; Spectrometry, Mass, Electrospray Ionization; Taxoids