Docetaxel metastatic breast cancer

The taxanes (e.g., paclitaxel and docetaxel) are a newer class of agents that rival the anthracyclines in their activity in metastatic breast cancer, becoming (arguably) the most active class of chemotherapy for this disease. 

Vinorelbine, a microtubule interactive agent, also has shown impressive response rates in metastatic breast cancer.60 Vinorelbine was approved by the FDA in 1994 for the treatment of non-small cell lung cancer. It is not approved for breast cancer, but response rates to vinorelbine range from 30% to 50%, with an overall 5% complete response rate in phase I and phase II studies in patients with advanced breast cancer. Importantly, paclitaxel, docetaxel, and vinorelbine do not appear to be cross-resistant with anthracyclines, which are arguably considered first-line treatment of metastatic breast cancer. 

Lyseng-Williamson KA, Fenton C. Docetaxel a review of its use in metastatic breast cancer. Drugs 2005 65(17) 2513-31. 

Docetaxel (DOXOTEL), a related drug, used in metastatic breast cancer. 

Phase 1 clinical trials demonstrated that Herceptin is safe and confined to the tumor. However, phase 2 trials indicated that the efficacy of the antibody is superior when given with chemotherapy (Pegram et al., 1998). Phase 3 trials have indicated that Herceptin, when added to conventional chemotherapy, can benefit patients with metastatic breast cancer that overexpresses HER-2, prolonging relapse and overall survival (Slamon et al., 2001). Similarly, extensive studies by Menden et al. (2001) support the weekly Docetaxel... 

This model was identified from data gathered in a clinical study [505] aiming to define a regular and tolerable dose of the epirubicin-docetaxel combination in first-line chemotherapy on 65 patients with metastatic breast cancer. Following the analysis of these data, parameters were set to... 

Viens, P., Roche, H., Kerbrat, P., Fumoleau, P., Guastalla, J., and De-lozier, T., Epirubicin-docetaxel combination in first-line chemotherapy for patients with metastatic breast cancer Final results of a dose-finding and efficacy study, American Journal of Clinical Oncology, Vol. 24, No. 4, 2001, pp. 328-335. 

Marty M, Cognetti F, Maraninchi D et al. (2005) Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor 2-positive metastatic breast cancer administered as first line treatment the M77001 study group, journal of Clinical Oncology 23 4247-4250. 

Many clinicians now prefer to use docetaxel (licensed to be used in combination with trastuzumab for metastatic breast cancer) instead of paclitaxel as it is more convenient to administer (1 hour infusion for docetaxel instead of 3 hours for paclitaxel) and clinicians generally have more experience of using this agent in breast cancer therapy. The pivotal trial of this combination shows superiority of docetaxel and trastuzumab over docetaxel alone in terms of overall survival, response rate and time to disease progression with little additional toxicity (Marty etal., 2005). 

Paridaens, R., Van Aaelst, E, and Georgoulias, V. (2003), A randomized phase II study of alternating and sequential regimens of docetaxel and doxorubicin as first line chemotherapy for metastatic breast cancer, Ann. Oncol., 14,433 440. 

An interaction of doxorubicin with the anti-HER2 receptor humanized monoclonal antibody, trastuzumab (Herceptin), has been reported. Most patients who received trastuzumab in early trials had been pretreated with anthracyclines. Despite this, preliminary information suggested that reduced systolic cardiac function was an adverse effect of trastuzumab (119). More recently, this problem has been further highlighted in a study of women with metastatic breast cancer (120). Patients who had not received prior anthracycline-containing adjuvant chemotherapy were at greater risk of cardiotoxicity when they received trastuzumab in combination with doxorubicin or cyclophosphamide (27 and 75% respectively), compared with only 11% of patients who received trastuzumab in combination with pachtaxel (120,121). The risk of cardiac events in patients treated with doxorubicin, cyclophosphamide, and trastuzumab increased markedly after a cumulative doxorubicin dose of 360 mg/m. This suggests synergistic cardiotoxicity with trastuzumab and doxorubicin. Trastuzumab is therefore currently licensed only for use in conjunction with pacli-taxel or docetaxel and not with conventional doxorubicin. 

Spielmann M, Tubiana-Huhn M, Namer M, Mansouri H, Bougnoux P, Tubiana-Mathieu N, Lotz V, Eymard JC. Sequential or alternating administration of docetaxel (Taxotere) combined with FEC in metastatic breast cancer a randomised phase II trial. Br J Cancer 2002 86(5) 692-7. 

Docetaxel is a taxane that is used in combination with doxorubicin in the treatment of metastatic breast cancer and as a single agent in metastatic lung cancer. 

Three of 14 patients in a phase 1 study of docetaxel plus vinorelbine for metastatic breast cancer developed colitis (6). A further three patients were identified in other studies of docetaxel. 

Shin E, Ishitobi M, Hiraoia M, Kazumasa F, Hideyuki M, Nishisho I, Toshiro S, Yasunori H, Tosimasa T. Phase I study of docetaxel administered by bi-weekly infusion to patients with metastatic breast cancer. Anticancer Res 2000 20(6C) 4721-6. 

Ibrahim NK, Sahin AA, Dubrow RA, Lynch PM, Boehnke-Michaud L, Valero V, Buzdar AU, Hortobagyi GN. Colitis associated with docetaxel-based chemotherapy in patients with metastatic breast cancer. Lancet 2000 355(9200) 281-3. 

Ando M, Watanabe T, Nagata K, Narabayashi M, Adachi I, Katsumata N. Efficacy of docetaxel 60mg/m in patients with metastatic breast cancer according to the status of anthracycline resistance. J Clin Oncol 2001 19(2) 336-42. 

A 48-year-old woman presents for her third cycle of docetaxel therapy for her metastatic breast cancer. Which of the following laboratory parameters are necessary to evaluate prior to administering the docetaxel ... 

Paclitaxel (Taxol ) and its semisynthetic analogue docetaxel (see Figure 5.1) are two of the most important chemotherapeutic drugs, currently used for the treatment of advanced ovarian cancer, metastatic breast cancer, melanoma, non-small-cell lung cancer, and Kar-posi s sarcoma [8,9], More recently, these drugs have been used for the treatment of neck, prostate, and cervical cancers [8, 9],... 

The taxanes (paclitaxel and docetaxel) are a newer class of agents that rival the anthracyclines in their activity in metastatic breast cancer, becoming (arguably) the most active class of chemotherapy for this disease. Since these agents are relatively new, adjuvant studies including them have not yet been incorporated into the overview metaanalysis. However, results from a few clinical trials have been reported and are reaching substantial follow-up to provide meaningful information. All trials have enrolled node-positive patients only, and all... 

Jones S, Erban J, Overmoyer B, et al. Randomized trial comparing docetaxel and paclitaxel in patients with metastatic breast cancer (Meeting abstract). San Antonio Breast Cancer Symposium 2003 A10. 

The two taxanes currently in use are paclitaxel, which is used in the treatment of ovarian cancer and metastatic breast cancer and docetaxel, which is used to treat metastatic breast cancer, small cell lung cancer and prostate cancer. 

Capecitabine is a pyrimidine analog. It is an oral systemic prodrug that is enzymatically converted to 5-fluorouracil (5-FU). Healthy and tumor cells metabolize 5-FU to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-flu-orouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms. First, they inhibit the formation of thymidine triphosphate, which is essential for the synthesis of DNA. Second, nuclear transcriptional enzymes can mistakenly incorporate FUTP during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis. Capecitabine is indicated in the treatment of resistant metastatic breast cancer alone or in combination with docetaxel, and colorectal cancer. 

Capecitabine is approved by the FDA for the treatment of (1) metastatic breast cancer in patients who have not responded to a regimen of paclitaxel and an anthracycline antibiotic (2) metastatic breast cancer when used in combination with docetaxel in patients who have had a prior anthracycline-containing regimen and (3) metastatic colorectal cancer for patients in whom fluoropyrimidine monotherapy is preferred. The recommended dose is 2500 mg/m daily, given orally in two divided doses with food, for 2 weeks followed by a rest period of 1 week. This cycle is then repeated two more times. 

Docetaxel acts by disrupting cells microtubular network, which is essential for mitotic and interphase cellular functions. Docetaxel binds to free tubulin and promotes the assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly. Docetaxel is indicated in locally advanced or metastatic breast cancer locally advanced or metastatic non-small-cell lung cancer. The first compound of this series, paclitaxel (Taxol), was isolated from the bark of the Western yew tree in 1971. Paclitaxel and its congenic, the semisynthetic docetaxel (Taxotere), exhibit unique pharmacological actions as... 

In a retrospective study including 46 patients with locally advanced or metastatic breast cancer, Takamura et al. evaluated the significance of [ Tc]MIBI uptake in early and delayed images in predicting tumor response to chemotherapy with epirubicin and cyclophosphamide or docetaxel [87]. Before starting chemotherapy, the patients underwent a [ Tc]MIBI SPECT study. The parameters extracted from SPECT images were the tumor-to-nor-mal tissue ratios (T/N) of [ Tc]MIBI uptake at 10 min (early phase) and at 180 min (delayed phase) and the retention index (RI) was calculated as follows RI = (T/N(d))/(T/N(e)). After chemotherapy, tumor response was determined by clinical examination. 

Freyer G, Hennebert P, Awada A, Gil T, Kerger J, Selleslags J, Brassinne C, Hccart M, de Valeriola D. Influence of amifostine on tiie toxicity and pharmacokinetics of docetaxel in metastatic breast cancer patients a pilot study. Clin Cancer Res (2002) 8, 95-102. 

Vasey PA, Roche H, Bisset D, Tenet C, VemilletL, Riva A, Ramazeilles C, AzIiN, Kaye SB, Twelves CJ. Phase I study of docetaxel in combinaticn widi cyclc hosph ide as fiik-line chemotherapy for metastatic breast cancer. BrJ Cancer (2002) 87,1072-8. 

Uses Bevacizumab, in combination with fiuoropyrimidine-based chemotherapy, is indicated for patients with metastatic carcinoma of the colon or rectum [155, 156 ", 157, 158 ] in combination with paclitaxel or docetaxel for first-line treatment of patients with metastatic breast cancer [159, 160 ] in addition to platinum-based chemotherapy, for first-line treatment of patients with unresectable, advanced, metastatic or recurrent non-small cell lung cancer, other than with predominantly squamous cell histology [161, 162 ] and in combination with interferon alfa-2a, for first-line treatment of patients with advanced and/or metastatic renal cell cancer [163, 164. ... 

Docetaxel is indicated, in combination with doxorubicin and cyclophosphamide, for adjuvant treatment of node-positive breast cancer and, in combination with doxorubicin, for treating locally advanced or metastatic breast cancer. It is also indicated as monotherapy or in combination with capecitabine for the treatment of locally advanced or metastatic breast cancer in patients who have relapsed or progressed after previous anthracycline or alkylating agents. It can be administered concurrently with trastuzumab, with which it is synergistic in vitro [1091], unlike paclitaxel, which appears to have simply an additive effect with trastuzumab [110 ]. 

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