[Efficacy and toxicity of trastuzumab combined with docetaxel for Her-2/neu overexpressing metastatic breast cancer].

BACKGROUND & OBJECTIVE: HER2 is overexpressed in approximately 20.0% to 30.0% of breast cancer patients. This alteration is associated with poor prognosis, and may affect response to hormonal therapy and chemotherapy. Chemotherapy combined with trastuzumab can significantly improve the treatment efficacy and survival of Her-2/neu overexpressing breast cancer patients. Docetaxel is an effective drug used for metastatic breast cancer recently. This study was to evaluate the efficacy and toxicity of trastuzumab combined with docetaxel in the treatment for metastatic breast cancer patients with overexpressed Her-2/neu. METHODS: Twenty-two metastatic breast cancer patients with overexpressed HER2/neu were entered into the study. Trastuzumab and docetaxel (75 mg/m(2)) were administrated on day 1 and repeated every 21 days. The initial dose of trastuzumab was 8 mg/kg and subsequent doses were 6 mg/kg. RESULTS: Overall 96 cycles were administrated to the 22 patients (medium three cycles per patient, range 2-6 cycles). All cases were evaluable. The overall response rate was 63.6% (14/22). Two patients achieved complete response (CR), 12 patients achieved partial response (PR), four patients achieved stable disease (SD), and four patients had progressive disease (PD). The median time to progression was 5.4 months. One year overall survival was 59.0%. The major toxicity was myelosuppression. A few patients had fever at first infusion of trastuzumab and minor heart failure. CONCLUSION: Trastuzumab combined with docetaxel is an effective and well-tolerated therapy for Her-2/neu overexpressing metastatic breast cancer.

[Preparation of docetaxel liposomes and their pharmacokinetics in rabbits].

BACKGROUND & OBJECTIVE: Docetaxel is used to treat non-small cell lung cancer, breast cancer and ovarian cancer. It is indissolvable and the solvent containing polysorbate-80 and 13% solution of ethanol is used for injections. Its clinical application is limited because of frequent severe hypersensitive responses. This study was to prepare docetaxel (DOC) liposomes and investigate their pharmacokinetics in rabbits after intravenous administration. METHODS: DOC liposomes, with or without modification of polyethylene glycol (PEG), were prepared by thin-film ultrasonic dispersion method. The entrapment efficiency and mean diameter of the liposomes were measured. After intravenous administration in rabbits, plasma DOC concentration was detected by solid phase extraction high-performance liquid chromatography (SPE-HPLC). The pharmacokinetic parameters were calculated and analyzed by 3p87 pharmacokinetic program. RESULTS: The entrapment efficiency of DOC liposomes was above 75%. The mean diameter was about 150 nm. The half-life of distribution (T(1/2alpha)) were (0.17+/-0.04) h for market docetaxel injection (M-DOC), (0.31+/-0.11) h for common DOC liposome (L-DOC), and (0.32+/-0.06) h for PEG-2000-modified DOC long circulating liposome (PEG-DOC-LCL); the half-life of clearance (T(1/2beta)) were (8.54+/-1.05), (11.18+/-1.33), and (10.51+/-1.13) h, respectively; the apparent volume of distribution (V(d)) were (13.66+/-3.62), (8.65+/-1.11), and (6.31+/-0.55) L, respectively; the area under the concentration-time curve from 0 to 24 h (AUC(0-->24)) were (13.45+/-2.44), (22.83+/-3.57), and (29.31+/-5.96) mg x (h x L)(-1), respectively; the area under the concentration-time curve from 0 to infinity h (AUC(0-->infinity)) were (15.07+/-2.76), (28.70+/-4.95), and (36.95+/-9.13) mg x (h x L)(-1), respectively; the clearance (CL) were (1.10+/-0.18), (0.54+/-0.08), and (0.42+/-0.07) L/h, respectively. CONCLUSION: The thin-film prepared DOC liposomes have high entrapment efficiency and small particle size. Both liposomes, especially PEG-DOC-LCL, can raise AUC and prolong the resident time of drugs in the blood circulating system.

[Analysis of antineoplastic drugs used in Cancer Center, Sun Yat-sen University, during the period of 1996-2005].

BACKGROUND & OBJECTIVE: Lately, the prevention, treatment and research of cancer have developed rapidly. Antineoplastic drugs have become one of the major measures for cancer therapy. Many new antineoplastic drugs have been discovered and prepared, and used to treat tumors. Cancer Center of Sun Yat-sen University is one of the biggest cancer hospitals in South China. The use of antineoplastic drugs of this center can reflect changes in this area. This study was to analyze and evaluate the situation and trend of antineoplastic drugs used in Cancer Center, Sun Yat-sen University from 1996 and 2005, in order to provide references for the rational use of drugs in clinical application. METHODS: Consumption of antineoplastic drugs was analyzed by sum and defined daily dose (DDDs) ranking. RESULTS: The costs of antineoplastic drugs occupied 31.0%-48.8% of all drugs from 1996 to 2005; and the average increasing ratio is 21.5%. The cost rate of anti-cancer vegetable drugs and other genus increased the quickest, while the total costs of alkylate increased the slowest during the ten years. Some new monoantibodies and gene drugs were continuously applied in clinical use. CONCLUSION: The direction of the research and development of antineoplastic drugs is towards high efficiency, low toxicity and individualized use.