Taxane treatment

Thomas ES, Gomez HL, Li RK, Chung H-C, Fein LE, Chan VF, Jassem J, Pivot XB, KJimovsky JV, de Mendoza FH, Xu B, Campone M, Lerzo GL, Peck RA, Mukhopadhyay P, Vahdat FT, Roche HH. (2007). Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol 25 5210-5217. 

Docetaxel offers an alternative taxane treatment in patients with platinum-refractory ovarian cancer. " Preclinical studies show that docetaxel has more potent in vitro activity than does paclitaxel. " Docetaxel has produced overall response rates of 20% to 40% in patients with platinum-sensitive and platinum-refractory advanced... 

Note that application in the particular indications is usually restricted either to patients expressing the target (e.g. trastuzumab, cetuximab, lapatinib, imatinib) and/or after failure of prior therapies (e.g. cetuximab, erlotinib, lapatinib, sutinib, dasatinib). Furthermore, for cancer treatment most tyrosine kinase inhibitors are applied in combination with conventional chemotherapeutic drugs, such as fluorouracil, taxanes, platin-based regimens, anthracylines and irinotecan or radiotherapy. 

Docetaxel, another taxane, binds to tubulin to promote microtubule assembly. The pharmacokinetics of docetaxel are best described by a three-compartment model, with an a half-life of 0.08 hours, a 3 half-life of 1.6 to 1.8 hours, and a terminal half-life of 65 to 73 hours.14 Docetaxel has activity in the treatment of breast, non-small cell lung, prostate, bladder, esophageal, stomach, ovary, and head and neck cancers. Dexamethasone, 8 mg twice daily for 3 days starting the day before treatment, is used to prevent the fluid retention syndrome associated with docetaxel and possible hypersensitivity reactions. The fluid... 

Recurrent SCLC is usually less sensitive to chemotherapy. If recurrence is more than 6 months after induction chemotherapy, the original regimen can be repeated. If recurrence occurs in less than 6 months but >3 months, treatment options include a taxane, gemcitabine, topotecan, irinotecan, CAV (cyclophosphamide, doxorubicin, and vincristine), and vinorelbine. 

O Shaughnessy, J.A. et al.. Weekly nanoparticle albumin paclitaxel (Abraxane) results in longterm disease control in patients with taxane-refractory metastatic breast cancer. Breast Cancer Research and Treatment, In Lippman, M.E., Editor-in-Chief, Special Issue 27th Annual San Antonio Breast Cancer Symposium, Kluwer Academic Publishers, Dordrecht, Vol. 88, Suppl. 1, 2004, Abstr. 1070. 

Paclitaxel is a taxane antineoplastic used in the treatment of primary ovarian cancer. 

Trastuzumab is licensed for the treatment of early breast cancer that overexpresses human epidermal growth factor receptor-2 (HER2). It may be administered as monotherapy or in combination with, for example, paclitaxel, docetaxel (taxanes) or anastrozole (aromatase inhibitors). Since trastuzumab can cause cardiotoxicity, concomitant use with anthracyclines such as... 

Campone M, Cortes-Funes H, Vorobiof D, et al, Vinflunine A new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy, Br J Cancer 95 1161-1166, 2006. 

Concurrent therapy for the treatment of more than three brain metastases using paclitaxel and radiation has been explored in a phase III trial (144). The hypothesis here being that high-dose paclitaxel in combination with cranial radiation should improve local control while providing systemically active amounts of chemotherapy. Unfortunately, there was no statically significant improvement in survival seen. There is certainly a place to further explore the benefits and toxicides experienced with concurrent taxane-based therapy with radiation in metastatic disease. The role of the taxanes in concurrent chemoradiotherapy with sarcomas and pediatric tumors has not been explored at this time. 

The success of taxane-based therapy in cancer treatment has stimulated interest in further improving its efficacy profile and in identifying new tubulin-active agents. Two taxane analogs, BMS-184476 and BMS-188797, demonstrate greater activity than paclitaxel or docetaxel in a number of human tumor cell lines as well as in rodent solid tumors and human xenografts (4,145). BMS-184476 was discovered to be more potent... 

The initial experience with the taxanes and especially with paclitaxel in the realm of combined modality therapy has had a substantial impact on the treatment of cancers both in the United States and worldwide. Paclitaxel delivered in concert with radiation provides a classical model of the development of clinically applicable treatment strategies from laboratory-based studies. The initial in vitro works of Tishler (39) and Choy (40) have translated in a very tangible way into approaches that are clinically applicable and in the next generation of randomized clinical trials their efficacy will be compared to more traditional chemotherapies in the combined modality setting. While the experience to date with both paclitaxel and docetaxel has been largely positive, the mortality rates in many of the solid tumor types remind us that much more needs to be done. 

The interdependence of methyl jasmonate with chitin- and chitosan-derived elicitors was studied using plant cell suspension cultures of Taxus canadensis. Induction of the biosynthesis of paditaxel and other taxanes was enhanced when methyl jasmonate and elicitors were added 8 days after culture transfer compared to treatments in which only methyl jasmonate or only elicitor was added. The optimal elicitor concentration using AT-acetylchitohexaose was 0.450 pM, but only in the presence of methyl jasmonate. Little, if any, induction of taxane formation occurred with the oligosaccharide alone. The optimal methyl jasmonate concentration was 200 pM using colloidal chitin or oligosaccharides of chitin and chitosan as elicitors. 

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