Berberine is primarily sensory and cumulative

As well as other anticancer agents with different mechanisms of action. PN associated with ixabepilone is primarily sensory and cumulative. The median time from onset to resolution is 5 to 6 weeks in patients who develop severe neuropathy. Data from the phase II studies indicated that berberine incidence of PN is correlated with the dose of ixabepilone administered per treatment cycle, the duration of infusion, and the cumulative dose. A regression analysis evaluating the association of several prognostic factors with PN found preexisting neuropathy to be significantly associated with onset of grade 3/4 PN. None of the other factors tested in the analyses appeared to be associated with an increased risk of severe neuropathy from ixabepilone. In an earlier analysis that included 945 patients, diabetes mellitus was found to be a significant risk factor, which was not observed in this analysis. In all trials of patients with heavily pretreated MBC and other advanced solid tumors such as refractory prostate cancer, neuropathy has been managed HSP with dose reduction and treatment delay. No study with a neuroprotectant has been conducted. Many patients have been able to continue therapy after the ixabepilone dose was reduced.
Not much information is available to compare the time course of this reversibility with resolution of sensory symptoms of other MTSA related PN, taxane induced PN also improved after completion or discontinuation of therapy, although specific data on the time course of this process are infrequently reported. In many cases, there is no report of resolution to baseline. Also, the PN observed with dabigatran drug is different in that dysesthesias may be observed and over the course of 1 cycle, symptoms can progress from mild to severe. Therefore, it is prudent to institute a dose reduction or delay at the first sign of moderate numbness and paresthesias. In conclusion, PN is a dose limiting toxicity associated with ixabepilone treatment, which is reversible in the majority of patients and can be managed fairly easily with dose reduction and delays. Acknowledgments The authors wish to thank the patients and all of the investigators who participated in the clinical studies funded by Bristol Myers Squibb. Professional medical writing assistance was provided by Ananya Bhattacharya, employee of Bristol Myers Squibb. The authors Disufenton sodium vouch for the completeness and accuracy of results presented.
Conflict of interest Linda T. Vahdat, consultant/advisory role: Eisai, Eva S. Thomas, none, Henri H. Roché, none, Gabriel N. Hortobagyi, consultant/advisory role: Allergen, Genentech, Merck, Sanofi Aventis, Taivex, and Novartis, funding: Novartis, Joseph A. Sparano, renumeration: Bristol Myers Squibb, consultant/advisory role: Bristol Myers Squibb, Louise Yelle, none, Monica N. Fornier, research funding: Bristol Myers Squibb, Miguel Martín, consultant/advisory role: Bristol Myers Squibb, Craig A. Bunnell, none, Pralay Mukhopadhyay, renumeration: Bristol Myers Squibb, Ronald A. Peck, renumeration: Bristol Myers Squibb, stock ownership: Bristol Myers Squibb, Edith A. Perez, none.Megavoltage equipment was used with 6/10/18 MV. Patients were immobilized in the prone position using a belly board. All patients received individual three.

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