OBJECTIVETo evaluate the efficacy and safety of combination chemotherapy with paclitaxel and carboplatin for advanced breast cancer (ABC).

METHODSFrom January 2001 to March 2006, 45 patients with ABC were treated with combination chemotherapy of paclitaxel and carboplatin. Patients received infusion of paclitaxel 175 mg/m2 on day 1 every 3 weeks or 75 mg/m2 on day 1, 8, 15 every 4 weeks. Carboplatin was administrated on day 2 with a dose of area under the time-concentration curve (AUC) being 5.

RESULTSThe median number of cycles was 3 (range, 2-6). The overall response rate was 62.2%. Median time to progression was 7.0 months (95% CI: 5.1-8.9). Median overall survival was 29.0 months (95% CI: 20.1-37.9). One year survival rate was 73.3%. Response rate for first line and second line treatment were 62.1% and 62.5% , respectively. No significant difference in response existed between visceral metastasis and soft tissue metastasis. The main side effects included nausea/vomiting, neurotoxicity, and hematologic toxicities. Grade III to IV adverse events included nausea/vomiting in 2 cases (4.4%), leukopenia in 17 cases (37.8%) , and alopecia in 6 cases (13.3%).

CONCLUSIONCombination of paclitaxel and carboplatin is active in treatment of ABC with an acceptable toxicity profile.

Alopecia ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; mortality ; pathology ; Carboplatin ; administration & dosage ; Drug Administration Schedule ; Female ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Metastasis ; Paclitaxel ; administration & dosage ; Postmenopause ; Premenopause ; Soft Tissue Neoplasms ; drug therapy ; secondary ; Survival Rate ; Vomiting ; chemically induced

Although continuous low-dose (metronomic [MET]) therapy exerts anti-cancer efficacy in various cancer models, the effect of long-term MET therapy for hepatocellular carcinoma (HCC) remains unknown. This study assessed the long-term efficacy of MET on suppression of tumor growth and spontaneous metastasis in a rat model of HCC induced by administration of diethylnitrosamine for 16 wk. The rats were divided into 3 groups: MTD group received intraperitoneal (i.p.) injections of 40 mg/kg cyclophosphamide on days 1, 3, and 5 of a 21-day cycle; Control and MET groups received i.p. injections of saline and 20 mg/kg cyclophosphamide twice a week, respectively. Anti-tumor and anti-angiogenic effects and anti-metastatic mechanisms including matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were evaluated. Twelve wk of MET therapy resulted in a significant reduction in intrahepatic tumors than control or MTD therapy. The MET group had fewer proliferating cell nuclear antigen-positive cells and decreased hypoxia-inducible factor-1alpha levels and microvessel density. Lung metastases were detected in 100%, 80%, and 42.9% in the control, MTD, and MET groups, respectively. MET therapy significantly decreased expression of TIMP-1, MMP-2 and -9. For mediators of pro-MMP-2 activation, MET therapy induced significant suppression in the TIMP-2 and MMP-14 level. The survival in the MET group was significantly prolonged compared to the control and MTD groups. Long-term MET scheduling suppresses tumor growth and metastasis via its potent anti-angiogenic properties and a decrease in MMPs and TIMPs activities. These results provide a rationale for long-term MET dosing in future clinical trials of HCC treatment.
Animals ; Antineoplastic Agents/*administration & dosage/*pharmacology ; Carcinoma, Hepatocellular/chemically induced/*drug therapy/mortality/pathology ; Cell Proliferation/drug effects ; Cyclophosphamide/*administration & dosage/*pharmacology ; Diethylnitrosamine ; Disease Models, Animal ; Gene Expression Regulation, Neoplastic/*drug effects ; Liver Cirrhosis/chemically induced ; Liver Neoplasms/chemically induced/*drug therapy/mortality/pathology ; Lung Neoplasms/drug therapy/pathology/secondary ; Male ; Matrix Metalloproteinases/metabolism ; Neovascularization, Pathologic/enzymology/physiopathology ; Rats ; Rats, Sprague-Dawley ; Survival Analysis ; Tissue Inhibitor of Metalloproteinases/metabolism ; Tumor Burden/drug effects