Epirubicin Docetaxel

Docetaxel + capecitabine Docetaxel 75 mg/m2 IV over 1 hour, day 1 Capecitabine 2000-2500 mg/m2 per day orally divided twice daily for 14 days Repeat cycles every 21 days Epirubicin + docetaxel" Epirubicin 70-90 mg/m2 IV bolus Followed by Docetaxel 70-90 mg/m2 IV over 1 hour Repeat cycles every 21 daysv Doxorubicin + docetaxel" Doxorubicin 50 mg/m2 IV bolus, day 1 Followed by Docetaxel 75 mg/m2 IV over 1 hour, day 1 Repeat cycles every 21 days"... 

Acyclovir Erythromycin Ivermectin Itraconazole Rifampin Actinomycin D Daunorubicin Doxorubicin Docetaxel Epirubicin Etoposide Imatinib Irinotecan Paclitaxel Vinblastine Vincristine Amprenavir Indinavir Nelfinavir Ritonavir Saquinavir Cyclosporine A Tacrolimus Digoxin Quinidine Verapamil Diltiazem Aldosterone Cortisol Corticosterone Dexamethasone Hydrocortisone Cyclosporine Metkephamid Enkephalin... 

C5H12O2 77-76-9) see Atorvastatin calcium Dibekacin Docetaxel Doxifluridine Epirubicin Indinavir sulfate lotrolan Misoprostol Oseltamivir acetonitrile... 

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. 

Pei, J., Zhang, C., Gokhale, PC., Rahman, A., Dritschilo, A., Ahmad, I., and Kasid, U. (2004) Combination with liposome-entrapped, ends-modified raf anti-sense oligonucleotide (LErafAON) improves the anti-tumor efficacies of cis-platin, epirubicin, mitoxantrone, docetaxel, and gemcitabine. Anticancer Drugs 15, 243-253. 

Vogt, U., Bielawski, K.P., Bosse, U., and Schlotter, C.M. (2004). Breast tnmour growth inhibition in vitro through the combination of cyclophosphamide/metotrexate/5-fluoro-uracil, epirubicin/cyclophosphamide, epimbicin/pachtaxel, and epirnbicin/docetaxel with the bisphosphonates ibandronate and zoledronic acid. Oncol Rep 12 1109-1114. 

Clinically significant cardiac insufficiency has been reported in a patient who was given epirubicin (316 mg/m ) followed by six cycles of docetaxel (100 mg/m /cycle) (118). 

Camptothecin analogs Irinotecan Topotecan Epipodophyllotoxins Etoposide Teniposide Antitumor antibiotics Bleomycin Dactinomycin Daunorubicin Doxorubicin Epirubicin Idarubicin Mitomycin Mitoxantrone Valrubicin Microtubule agents Docetaxel Paclitaxel Vinblastine Vincristine Vinorelbine Enzymes Asparaginase Pegasparaginase Metals... 

Cytotoxic drags that have been used alone and in combination as adjuvant therapy in breast cancer include doxorubicin, epirubicin, cyclophosphamide, methotrexate, fluorouracil, paclitaxel, docetaxel, melphalan, prednisone, vinorelbine, and vincristine. The most common combination chemotherapy regimens employed in the adjuvant and metastatic setting are listed in Table 125-11. 

Among all ABC transporters, P-gp, also known as MDRl protein, ABCBl or CD243, is probably the most studied and characterized member. It was first found as a 170-kDa ATP-dependent membrane glycoprotein that acts as a drug efflux pump [15], P-gp is a broad-spectrum transporter, capable of transporting several structurally and functionally unrelated substrate molecules. Its substrates are typically hydrophobic, amphipathic products, including many chemotherapeutic compounds used for cancer treatment, e.g., vinca alkaloids (vincristine, vinblastine), taxanes (paclitaxel, docetaxel), epipodophyllotoxins (etoposide, teniposide), anthracyclines (doxorubicin, daunorubicin, epirubicin), topotecan, dactinomycin, and mitomycin-C [37]. 

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. 

Toxicity associated with combinations of paclitaxel with doxorubicin or epirubicin depends on the order of administration. Some modest pharmacokinetic changes may occur when paclitaxel and epirubicin are given together. The combination of doxorubicin and pacUtaxel is more cardiotoxic than doxorubicin alone paclitaxel increases doxorubicin levels but doxorubicin does not alter pacUtaxel levels. Docetaxel may modestly affect the pharmacokinetics of epirubicin and doxorubicin. 

Conversely, a study of the combination of docetaxel and epirubicin did not find that the sequence of drug administration affected the pharmacokinetics of epirubicin, nor was there any difference in toxicity. In another study, 16 patients with breast cancer had a transient but significant increase in epirubicin plasma levels during the subsequent infusion (after an interval of 1 hour) of docetaxel 75 mg/m, which was not seen if the docetaxel was given within 10 minutes of epiruhicin. ... 

Studies in mice have found that the taxanes docetaxel and paclitaxel, and the vehicle used for paclitaxel Cremophor, may all modify the distribution and metabolism of doxorubicin increasing its levels in the heart, liver and kidneys. This may contribute to the cardiac toxicity seen during use with paclitaxel. Similarly, m vitro studies in human myocardium showed that paclitaxel and docetaxel increased the conversion of doxorubicin to doxorubicinol, the metabolite that is thought to be responsible for cardiotoxicity. An in vitro study on the effect of paclitaxel and Cremophor on epirubicin metabolism in human blood found that paclitaxel slightly decreased production of epirubicinol. A marked inhibition of epirubicinol production occurred in the presence of Cremophor, hut because of the low... 

Bergaglio M, Del Mastro L, Rosso R Comparative effects of paclitaxel and docetaxel cn tile metabolism and pharmacokinetics of epirubicin in breast cancer patients. J Chn Oncol (1999) 17, 1132-40. 

Lunardi G, Venturini M, Vannozzi MO, Tolino G, Del Mastro L, Bighin C, Schettini G, Esposito M Influence of alternate sequences of epirubicin and docetaxel on the pharmacokinetic behaviour of botii drugs in advanced breast cancer. Ann Oncol (2002) 13, 280-5. 

Some evidence su ests ondansetron may modestly affect the pharmacokinetics of cyclophosphamide and cisplatin but it does not appear to affect those of carmustine. Ondansetron did not affect the in vitro activity of epirubicin, bleomycin, cisplatin or es-tramustine. Cisplatin and fluorouracil do not affect the pharmacokinetics of ondansetron. In in vitro studies granisetron potentiated the cytotoxic effects of epirubicin, had an additive effect on bleomycin and estramustine activity and appeared not to affect the metabolism of docetaxel and paclitaxel. 

Examples for good siurogate markers include an intermediate filament, which is released from apoptotic cancer cells during chemotherapy, and a collagen fragment which indicates bone decay [39-40]. Cyokeratin 18 is an efficient biomarker to measure the effect of breast cancer treatment via combination chemotherapy such as docetaxel or cyclophosphamide/epirubicin/5-fluorouracil (CEF). 

Cardiovascular Heart failure (New York Heart Association classes II-IV) has been observed in patients receiving trastuzumab, alone or in combination with paclitaxel or docetaxel, particularly after chemotherapy containing an anthracycline (doxorubicin or epirubicin) [303, 304, 305, 306. It can be moderate or severe and can be fatal. The results of many randomized trials have shown that the degree of cardiotoxicity is generally acceptable the incidence of cardiac damage caused by trastuzumab was 0.4-4.1% [307 ]. Older age, lower left ventricular ejection fraction, and antihypertensive medications are associated with an increased risk of cardiac dysfunction in patients receiving trastuzumab [308 "]. The cardiac dysfunction associated with trastuzumab is usually reversible on withdrawal and standard medical therapy [309 ]. In one case, trastuzumab-associated cardiomyopathy presented with complete left bundle-branch block mimicking acute coronary syndrome [310" ]. 

Kluger N, Jacot W, Frouin E, Rigau V, Poujol S, Dereure O, et al. Permanent scalp alopecia related to breast cancer chemotherapy by sequential fluorouracil/epirubicin/cyclophosphamide (FEC) and docetaxel a prospective study of 20 patients. Ann Oncol 2012 23(ll) 2879-84. 

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