原产地英文商品名：DOCETAXEL(TAXOTERE GENERIC) 20mg/2ml/Vial
本品和顺铂或长春瑞宾或阿霉素合用，提示有益的结果。与酮康唑合用，可能发生不良相互作用，使用时要格外小心。【用法用量】推荐剂量为每3周用75 mg/m2，静脉滴注1 hr。
Docetaxel is a semisynthetic derivative of the readily available taxane precursor 10-deacetyl baccatin III, which is extracted from the needles of the european yew tree, taxus baccata, and other taxus species. Like paclitaxel,this agent alters microtubule dynamics by decreasing microtubule disassembly,stabilizing polymerized tubulin,and promoting microtubule assembly.Docetaxel differs from paclitaxel on the c10 taxane ring position, and on the ester side chain attached at C13. Clinical antitumor activities of the two taxane are similar, although doxetaxel appears to be more potent than paclitaxel with reguard to its antimicrotubule effects and cytotoxicity in vitro. However, this does not necessarily translate into enhanced therapeutic efficacy because it may also portend more severe toxicity at identical drug concentrations in vivo.Unlike paclitaxel,docetaxel has linear pharmacokinetics,a longer serum half-life, and longer intracellular retentionINDICATIONSImpressive antitumor activity in patient with metastatic breast cancer as first-line or salvage treatment, non-small cell lung cancer as first-line or in platinum-refractory ovarian cancer. Currently approved by the US food and drug administration as second-line treatment following treatment with anthracyclines in patients with metastatic breast cancer. Its role as a component of adjuvant and neoadjuvant chemotherapy following the local treatment of early-stage breast cancer, and of first-line chemotherapy for locally advanced and metastatic non-small cell lung cancer, are being eva luated.Regulatory approval has been granted in many countries for the treatment of patient with locally advanced or metastatics non-small cell lung cancer,because agent has shown a survival advantage when used in the second-line setting following platinum-based therapy.In addition impressive activity in previously treated patients with carcinomas of the ovary,endometrium,head and neck,esophagus,stomach,urinary bladder,prostate, and small cell lung,as well as lymphomas and other neoplasms.Clinical antitumor spectra for paclitaxel and docetaxel are similarDOSAGE AND ADMINISTRATIONRecommended dosage ranges from 60-100 mg/m2 given IV only 1 h every 3 wks.However,75-100 mg/m2 is commonest dose range in clinical practice.Similar to paclitaxel,weekly treatment has been associated with lower hematologic toxicity than 3 weekly schedules and appears to be well torerated at 36 mg/m2 /wk. In patient without hyperbilirubinemia,dose reduction of 25% are recommended with elavated hepatic transaminase (>1.5-fold) and alkaline phosphatase (>2.5-fold) regardless of whether the elevation are due to hepatic metastases.However, more substantial reduction (50 % or greater) may be required for patients who have moderate or severe hepatic excretory dysfunction.Dose modification are not required for impaired renal function or third space fluid collections.Premadication is required, with dexamethasone 8 mg PO twice daily,usually given for 3-5 days starting 1-2 days before treatment to minimize risk of fluid retention and hypersensitivity reactions. H1 – and H2 -histamine antagonists can also be given IV 30 minutes before docetaxelPHARMACOKINETICSLinear and are well fit by a three-compartment model. The agent binds avidly to plasma proteins(>80%-90%) and is widely distributed with a steady-state volume of distribution of 74 L/m2 . Does not cross the blood-brain barrier. Terminal half-life (T1/2g) ranges ranges from 10-15 h. It is cleared primarily by hepatic metabolism,with fecal excretion accounting for 70%-80% of drug. Urinary excretion accounts for less than 10%. CytochromeP450 mixed function oxidases, in particular isoforms CYP3A4 and CYP3A5, are mainly responsible for hepatic metabolism. Principal pharmacokinetic determinants of toxicity are drug exposure to biologically relevant plasma concentrations. Docetaxel exhibits a wide interpatient variation in clearance that results in varying degrees of toxicity, perhaps due to variability in CYP3A activity. The measurement of metabolites of substrates of CYP-3A, such as erythromycin in the erythromycin breast test, may predict CYP3-A activity, docetaxel clearance and toxicitySPECIAL PRECAUTIONSSevere hypersensitivity reactions are uncommon,with dyspnea,hypotension,and flushing occuring is less than 1% of patients. In patients with impaired liver function,dose reductions recommended. Dose modification are not required for renal impairment or third-space fluid collectionsDRUG INTERACTIONSInteractions with other classes of drugs that can effect the cytochrome P450 system are predicted based on interactions demonstrated for paclitaxel (See drug interactions in paclitaxel section).However,neither significant pharmacokinetic or toxicologic drug-drug interactions between docetaxel and the anthracyclines have been documented,which may reflect differences in taxane formulation and/or potencies that may lead to differences in the number of molecules available for competition for clearance mechanisms with the anthracyclinesTOXICITIESHematologic: neutropenia toxicity limits dosage of doxytaxel. It is not cumulative and treatment delays due to incomplete recovery of neutrophil counts are unusual.At 100 mg/m2 ,using the 1-h schedule,nadir counts are frequently less than 500/mL, which usually occur on day 9 with recovery by days 15-21. The most important predictor of neutropenia is the extent of previous therapy. Severe thrombocytopenia and anemia are infrequent;Hypersensitivity: despite not being formulated in polyoxyethylated castor oil,docetaxel caused hypersensitivity reactions in approximately 31% of patients treated without premedication on early trials,which occurred within first few minutes of the initial two courses. Symtoms resolved rapidly with cessation of therapy.Treatment was usually recommended without adverse effect. Most reactions were minor with flushing,wheezing,chest tightness,anxiety,and low back pain.Dyspnea,hypotension,and bronchospasm leading to cyanosis were less common.Premedication reduces the risk hypersensitivity reactions;Fluid retention: causes a unique fluid retention syndrome resulting in weight gain,edema,pleural effusions,and ascites,possibly resulting from increased capillary permeability resulting in fluid leakage from vascular compartment. It is not usually a significant problem until a cumulative dose of more than 400-mg/m2 docetaxel has been administered in the absence of corticosteroid premedication.Premeddication with corticosteroids and H1 – and H2 -histamine antagonists decreased incidence of fluid retention as a function of cumulative dose;Dermatologic: alopecia;between 50% and 75% of patients develop an erythematous pruritic maculopapular rash affecting forearms and hands.Premedication decreases rash incidence.Superficial desquamation of the hands and feet and palmar-plantar erythrodysesthesia occur that may respond to oral pyridoxine 50 mg three times daily.Onychodystrophy with brown brittle nails,ridging,onycholysis,and soreness is common. Phlebitis along infusion course and at injection site is occasionally noted,but severe tissue necrosis following extravasation rare;Neuromuscular : similar but less marked than with paclitaxel. Mild to moderate peripheral sensory neuropathy predominates,in approximately 40% of chemotherapy-native patients.Motor effects are less common. Severy toxicity is unusual in the absence of an underlying comorbid neurologic disorder (eg, diabetes, alcoholism).Arthralgia and myalgia following treatment are not uncommon but usually short-lived.Other : severy lethargy and malaise occur infrequently,particularly in patients who have have received large cumulative doses o0n a weekly basis. Stomatitis more frequent than with -paclitaxel. Nausea,vomiting,and diarrhea are uncommon.Little evidence suggests cardiotoxicityPATIENT MONITORINGMonitor for fluid retention,neurotoxicity,and myelosuppression and hepatic dysfunction, the later of which may require reduced dosage.Treatment is usually withheld until neutrophil count exceeds 1500 cells/mm3NURSING INTERVENTIONSObserve patient for hypersensitivity reactions, which usually occur in the first two courses within minutes of therapy.Care against extravasation is important,although extravasation reactions do not usually cause necrosis.Avoid infusion sets containing PCVPATIENT INFORMATIONAdvise patient of risk of hypersensitivity reactions,neutropenic sepsis,and fluid retention.Female patients should be advised to avoid pregnancy during treatmentFORMULATIONProprietary name is Taxotere (aventis Pharmaceuticals, Bridgewater, NJ). Formulated with polysorbate 80 in sterile vials containing 40 mg/mL.Unopened vials should be strored between 2-8癱 and protected from light.It is diluted with the supplied sterile diluent containing 13% alcohol to a final premix solution of 10 mg/ml, which is stable for up to 8 h at room temperature and must be diluted in either 0.9% NaCl solution or 5% dextrose solution to achieve a final concentration of 0.3 to 0.9 mg/mL.After preparation,use solution as soon as possible.