Docetaxel

The barks of Taxus chinensis (Pilger) Rehd.

Docetaxel, a new taxoid family member originally derived from the needles of the European Yew tree Taxus baccata, is a potent chemotherapeutic agent that acts as a spindle poison to inhibit microtubule dynamics and cell cycle arrest through promoting microtublin assembly and stabilizing the polymers against depolymerization. Docetaxel has demonstrated strong in vivo and in vitro antitumor activities against a broad range of cancers including breast, lung, ovarian, head and neck, and gastric cancers. Previous studies have shown that docetaxel exertss stronger cytotoxicity than other chemotherapeutic agents against ovarian carcinoma cell lines, in which the cytotoxicity of docetaxel is 1.2-2.6 times greater than that of paclitaxel and over 1000 times greater than that of cisplatin or etoposide.

Reference

N Katsumata. Docetaxel: an alternative taxane in ovarian cancer. British Journal of Cancer (2003) 89 (Suppl 3), S9-S15

Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer.[Pubmed:15470214]

N Engl J Med. 2004 Oct 7;351(15):1513-20.

BACKGROUND: Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive androgen-independent prostate cancer. We compared Docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic, hormone-independent prostate cancer. METHODS: We randomly assigned 770 men to one of two treatments, each given in 21-day cycles: 280 mg of estramustine three times daily on days 1 through 5, 60 mg of Docetaxel per square meter of body-surface area on day 2, and 60 mg of dexamethasone in three divided doses before Docetaxel, or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily. The primary end point was overall survival; secondary end points were progression-free survival, objective response rates, and post-treatment declines of at least 50 percent in serum prostate-specific antigen (PSA) levels. RESULTS: Of 674 eligible patients, 338 were assigned to receive Docetaxel and estramustine and 336 to receive mitoxantrone and prednisone. In an intention-to-treat analysis, the median overall survival was longer in the group given Docetaxel and estramustine than in the group given mitoxantrone and prednisone (17.5 months vs. 15.6 months, P=0.02 by the log-rank test), and the corresponding hazard ratio for death was 0.80 (95 percent confidence interval, 0.67 to 0.97). The median time to progression was 6.3 months in the group given Docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone (P<0.001 by the log-rank test). PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients, respectively (P<0.001), and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease, respectively (P=0.30). Grade 3 or 4 neutropenic fevers (P=0.01), nausea and vomiting (P<0.001), and cardiovascular events (P=0.001) were more common among patients receiving Docetaxel and estramustine than among those receiving mitoxantrone and prednisone. Pain relief was similar in both groups. CONCLUSIONS: The improvement in median survival of nearly two months with Docetaxel and estramustine, as compared with mitoxantrone and prednisone, provides support for this approach in men with metastatic, androgen-independent prostate cancer.

Docetaxel rechallenge after an initial good response in patients with metastatic castration-resistant prostate cancer.[Pubmed:24947139]

BJU Int. 2015 May;115(5):744-52.

OBJECTIVE: To evaluate the benefit of Docetaxel rechallenge in patients with metastatic castration-resistant prostate cancer (mCRPC) relapsing after an initial good response to first-line Docetaxel. PATIENTS AND METHODS: We retrospectively reviewed the records of consecutive patients with mCRPC with a good response to first-line Docetaxel [serum prostate specific antigen (PSA) decrease >/=50%; no clinical/radiological progression]. We analysed the impact of management at relapse (Docetaxel rechallenge or non-taxane-based therapy) on PSA response, symptomatic response (performance status/pain/analgesic consumption), and overall survival (OS). We used multivariate stepwise logistic regression to analyse potential predictors of a favourable outcome. RESULTS: We identified 270 good responders to first-line Docetaxel. The median progression-free interval (PFI) was 6 months from the last Docetaxel dose. At relapse, 223 patients were rechallenged with Docetaxel (82.5%) and 47 received non-taxane-based therapy. There was no significant difference in median OS {18.2 [95% confidence interval (CI) 16.1-22.00] and 16.8 [95%CI 13.4-21.5] months, respectively, P = 0.35}. However, good PSA response and symptom relief/stable disease were more frequent on Docetaxel rechallenge (40.4% vs 10.6%, P < 0.001 for PSA). A PFI of >6 months and added estramustine predicted a good PSA response and symptomatic response on Docetaxel rechallenge but only a PFI of >6 months predicted longer OS. Haemoglobin (<13 g/dL) and pain were associated with reduced OS. Docetaxel rechallenge increased the incidence of grade >/=3 sensory neuropathy, nail disorders and asthenia/fatigue. CONCLUSIONS: Docetaxel rechallenge is a management option for responders to Docetaxel with a PFI of >6 months, but did not prolong survival. Potential benefits should be weighed against the risk of cumulative toxicity.

Balancing activity and tolerability of neoadjuvant paclitaxel- and docetaxel-based chemotherapy for HER2-positive early stage breast cancer: sensitivity analysis of randomized trials.[Pubmed:25683304]

Cancer Treat Rev. 2015 Mar;41(3):262-70.

Paclitaxel and Docetaxel represent the most adopted taxanes in the neoadjuvant treatment of HER2-positive breast cancer. Questions still remain with regard to their difference in terms of activity and tolerability. Events for pathological complete response (pCR), severe and febrile neutropenia (FN), and severe neurotoxicity were pooled by adopting a fixed- and random-effect model. A sensitivity analysis to test for the interaction between paclitaxel and Docetaxel was accomplished. Absolute differences with 95% confidence intervals (CIs) and the number of patients needed to treat/harm (NNT/NNH) were calculated to derive the Likelihood of being Helped or Harmed (LHH). Data from 15 trials (3601 patients) were included. Paclitaxel significantly increases pCR rate by 6.8% in comparison with Docetaxel (43.4%, 95% CI 41.1-45.7% versus 36.6%, 95% CI 34.3-39.0%, p=0.0001), regardless of the chemotherapy backbone, with an absolute difference of 9% and 9.2% for anthracycline-based or free-regimens. Paclitaxel significantly improves pCR versus Docetaxel with a single HER2-inhibition by 6.7% (p=0.0012), with no difference if combined with a dual HER2-inhibition. Severe neutropenia and FN are significantly lower with paclitaxel, with an absolute difference of 32.4% (p<0.0001) and 2.5% (p=0.0059), respectively. Conversely, severe neurotoxicity is slightly higher with paclitaxel (3%, p=0.0001). The LHH ratio calculated for pCR and severe neutropenia is 2.0 and 0.7 for paclitaxel and Docetaxel. Although the activity of neoadjuvant paclitaxel and Docetaxel HER2-positive breast cancer is considered similar, the slight advantage in pCR, the significantly lower neutropenia and FN, do favor paclitaxel (in the weekly fashion) over Docetaxel, despite the slightly worst neurotoxicity.

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors.[Pubmed:16703123]

Drugs Today (Barc). 2006 Apr;42(4):265-79.

Docetaxel is a semisynthetic taxane that acts by binding to the beta-tubulin subunit of the microtubules, resulting in cell-cycle arrest and apoptosis. It is approved for the management of early and advanced breast cancer, locally advanced and metastatic lung cancer and hormone refractory prostate cancer. Docetaxel has also shown significant antitumor activity in ovarian and gastric tumors and has very recently been approved for the treatment of advanced gastric cancer. Severe neutropenia is the major dose-limiting toxicity with the approved three-weekly regimens, although alternate weekly schedules with less myelotoxicity have been developed for patients with poor bone marrow reserve. This article will review the pharmacology and trials leading to the clinical approval of this agent.

Docetaxel: a review of its use in metastatic breast cancer.[Pubmed:16296875]

Drugs. 2005;65(17):2513-31.

Docetaxel (Taxotere), a cytotoxic taxane, is an antimicrotubule agent effective in the treatment of patients with breast cancer. The clinical profile of Docetaxel as an effective cytotoxic agent in the treatment of metastatic breast cancer is well established. As yet, no single standard regimen has been identified as optimal for the treatment of patients with metastatic breast cancer after failure of prior chemotherapy. However, the efficacy of Docetaxel monotherapy administered every 3 weeks as a 1-hour infusion is similar to or better than that of doxorubicin, paclitaxel and fluorouracil plus vinorelbine, and better than that of methotrexate plus fluorouracil or mitomycin plus vinblastine. Although Docetaxel is associated with neutropenia and other adverse events, its overall tolerability profile is generally acceptable in the majority of patients. Docetaxel, therefore, is an effective option in the treatment of patients with metastatic breast cancer after failure of prior chemotherapy.

Docetaxel (RP-56976) is an antineoplastic agent and inhibits microtubule depolymerization with an IC50 value of 0.2 μM. Docetaxel (RP-56976) is a semisynthetic analog of taxol and attenuates the effects of bcl-2 and bcl-xL gene expression. Docetaxel (RP-56976) arrests the cell cycle at G2/M and leads to cell apoptosis.

Docetaxel,114977-28-5,Natural Products,Mitotic, buy Docetaxel , Docetaxel supplier , purchase Docetaxel , Docetaxel cost , Docetaxel manufacturer , order Docetaxel , high purity Docetaxel