Docetaxel Cyclophosphamide

Breast CMF cyclophosphamide + methotrexate + 5-fluorouracil AC doxorubicin (Adriamycin) + cyclophosphamide Docetaxel ... 

N, former school director, now unemployed. Breast cancer, stage 2, diagnosed in 2002 at age thirty-six. (Treatment lumpectomy, radiation. Chemo doxorubicin, cyclophosphamide, docetaxel, and trastuzumab [Herceptin].)... 

AZATHIOPRINE CHLORAMBUCIL, CISPLATIN, CYCLOPHOSPHAMIDE, CYTARABINE, DACTINOMYCIN (ACTINO-MYCIN D), DAUNORU-BICIN, DOCETAXEL, DOXORUBICIN, ETOPO-SIDE, FLUOROURACIL, MELPHALAN, MERCAPTO-PURINE, MITOXANTRONE, VINCA ALKALOIDS t risk of myelosuppression and immunosuppression. Deaths have occurred following profound myelosuppression and severe sepsis Additive myelotoxic effects. Azathioprine is metabolized to 6-mercatopurine in vivo, which results in additive myelosuppression, immunosuppression and hepatotoxicity Avoid co-administration... 

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. 

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. 

Clinically important, potentially hazardous interactions with altretamine, amikacin, aminoglycosides, antineoplastics, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, corticosteroids, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, estramustine, etoposide, fludarabine, fluorouracil, gemcitabine, gentamicin, hydroxyurea, idarubicin, ifosfamide, indomethacin, kanamycin, levamisole, lomustine, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, mitoxantrone, neomycin, pentostatin, plicamycin, procarbazine, streptomycin, streptozocin, thioguanine, thiotepa, tobramycin, tretinoin, uracil, vinblastine, vincristine, vinorelbine... 

Clinically important, potentially hazardous interactions with aluminum, aminophylline, aspirin, chlorambucil, cimetidine, clarithromycin, cyclophosphamide, cyclosporine, dicumarol, diuretics, docetaxel, estrogens, grapefruit juice, indomethacin, influenza vaccines, itraconazole, ketoconazole, lansoprazole, live vaccines, methotrexate, montelukast, omeprazole, oral contraceptives, pancuronium, phenobarbital, phenytoin, ranitidine, rifampicin, rifampin, timolol, tolbutamide, vitamin A... 

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. 

AC, doxorubicin, cyclophosphamide BCIRG, Breast Cancer International Research Croup CALCB, Cancer and Leukemia Croup B FAC, fluorouracil, doxorubicin, cyclophosphamide NSABP, National Surgical Adjuvant Breast and Bowel Project Pac, paclitaxel TAC, docetaxel, doxorubicin, cyclophosphamide. 

Docetaxel and prednisone have recently been shown to improve survival in hormone-refractory metastatic prostate cancer and should be considered standard therapy. Single agents with modest activity in prostate cancer include cyclophosphamide, estramustine, 5-fluorouracil, methotrexate, dacarbazine, mitoxantrone, doxorubicin, pachtaxel, gemcitabine, vinorelbine, and cisplatin. If disease stabilization is included as a favorable response, response rates np to 46% have been reported. Several trials have evalnated the varions combination regimens containing the most active single agents. ... 

Docetaxel Clomipramine Sulfinpyrazone (aromatic hydroxylation) Cyclophosphamide... 

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. 

In a study, 627 patients with breast cancer were given either doxorubicin 50 mg/m with docetaxel 75 mg/m, or doxorubicin 60 mg/m with cyclophosphamide 600 mg/m postoperatively for 4 courses to assess disease-free survival at 5 years. The study was terminated prematurely because of the high risk of life-threatening complications in those given doxorubicin with docetaxel (2 deaths associated with drug toxicity and one case of perforated peritonitis in patients with febrile neutropenia). The incidence of febrile neutropenia was 40.8% and 7.1% in the doxorubicin-docetaxel and doxorubicin-cyclophosphamide groups, respectively. ... 

Aprepitant had no effect on the pharmacokinetics of a single dose of docetaxeL The activation of cyclophosphamide and thiotepa was slightly lower in patients receiving aprepitant, but this was not clinically relevant. However, because of the possibility of increased toxicity the manufacturer recommends caution with antineoplastics principally metabolised by the cytochrome P450 isoenzyme CYP3A4, particularly irinotecan, and also etoposide, vinorelbine, paclitaxel, ifosfamide, imatinib, vinblastine and vincristine, although there appears to be some limited evidence of safe concurrent use. 

In the short-term, aprepitant is an inhibitor of the cytochrome P450 isoenzyme CYP3A4, and might therefore reduce the activation of antineoplastics activated by this isoenzyme (cyclophosphamide, thiotepa), or increase the toxicity of antineoplastics metabolised by this enzyme (docetaxel, irinotecan). 

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. 

The AUCs of ifosfamide and its metabolites were lower when ifosfamide was given immediately after docetaxel than when it was given 24 hours before docetaxel, due to increased clearance. Docetaxel pharmacokinetics were unaltered by ifosfamide. This supports the evidence that the maximum tolerated dose is greater when ifosfamide is given after docetaxel. The mechanism is unknown, but it has been suggested that docetaxel may competitively inhibit the activation of ifosfamide by the cytochrome P450 isoenzyme CYP3A4. These results showthat the toxicity, and possibly efficacy, of the combination are schedule dependent. More study is needed. Cyclophosphamide does not appear to alter doeetaxel pharmacokinetics. For full details see also Taxanes + Cyclophosphamide , p.661. 

There is some evidence to suggest that the toxicity associated with combinations of paclitaxel and cyclophosphamide is dependent on the order of administration. Results from one study indicate that docetaxel pharmacokinetics are unaltered by cyclophosphamide. 

The pharmacokinetics of docetaxel were not altered by pretreatment with an intravenous bolus dose of cyclophosphamide in a phase I study. For a report that the pharmacokinetics of docetaxel are not affected by ifosfa-mide, see Cyclophosphamide or Ifosfamide + Taxanes , p.628. 

A study in 9 patients with a variety of malignant diseases found that treatment with antineoplastics reduced the absorption of a single 160-mg oral dose of verapamil. The verapamil AUC in 8 patients was reduced by 40% (range 7 to 58%), and one patient conversely had a 26% increase. Five patients reeeived a modified COPP regimen (cyclophosphamide, vincristine, procarbazine, prednisone) and four received VAC (vindesine, doxornbicin, cisplatin). It is believed that these antineoplastics damage the lining of the upper part of the small intestine, which impairs the absorption of verapamil. The clinical relevance of this reduction does not appear to have been studied. Note that verapamil may affect levels of anthracyclines , (p.611), etoposide , (p.631), and possibly docetaxel , (p.662). In addition, nifedipine may affect the levels of vincristine , (p.671). 

In mouse mammary tumor cells, treatment with black cohosh increased the cytotoxicity of doxorubicin and docetaxel and decreased the cytotoxicity of cisplatin, but did not alter the effects of radiation or 4-hydroperoxycyclophos-phamide (an analog of cyclophosphamide that is active in cell culture) (Rockwell et al. 2005). 

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). 

Paclitaxel, given 3-weekly, was previously indicated in the adjuvant treatment of nodepositive breast cancer, following anthracycline and cyclophosphamide chemotherapy, but a large randomized study showed that weekly paclitaxel or 3-weekly docetaxel regimens are superior [3 ]. Thus, in the UK NICE recommends the use of docetaxel rather than paclitaxel as adjuvant treatment for lymph node-positive breast cancer [4 ]. 

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 ]. 

Unlike paclitaxel, docetaxel does not appear to affect the metabolism of doxorubicin. Thus, the combination of docetaxel arul doxorubicin does not increase the risk of cardiotoxicity, compared with doxorubicin alone [145 ] or doxorubicin + cyclophosphamide combination chemotherapy [146 ]. 

Nabholtz JM, Falkson C, Campos D, Szanto J, Martin M, Chan S, Pienkowski T, Zaluski J, Pinter T, Krzakowski M, Vorobiof D, Leonard R, Kennedy I, Azli N, Murawsky M, Riva A, Pouillart P. TAX 306 Study Group. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer results of a randomized, multicenter, phase HI trial. J Clin Oncol 2003 21(6) 968-75. 

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