[Show abstract][Hide abstract] ABSTRACT: Neoadjuvant epirubicin/docetaxel (ET) combination chemotherapy was administered to breast cancer patients in order to investigate their clinical and pathological response. Moreover, the breast-conserving surgery (BCS) rate, disease-free (DFS) and overall survival (OS), safety profile and the correlation of biological markers were investigated.
Out of the 46 enrolled patients, 45 patients were analyzed for clinical response, and 40 patients were examined for pathological response. Estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor type2 (HER2) expression were examined immunohistologically.
The median tumor size was 4.5 cm in diameter. Complete (CR) and partial responses were seen in 3 and 30 patients, respectively. A pathological CR was achieved in 4 patients and correlated with ER and PgR negativity. Moreover, BCS was performed on 16 patients. The 5-year cumulative DFS was 60.7% and OS was 91.8%.
ET therapy is clinically effective with a pathological CR rate of 10% for patients with a large tumor, and should be considered as a neoadjuvant treatment option.
No preview · Article · Aug 2012 · Anticancer research
[Show abstract][Hide abstract] ABSTRACT: This study examined the efficacy and tolerability of docetaxel(DOC)in combination with epirubicin(EPI)as the first-line treatment for patients with advanced and recurrent breast cancer. A total of 56 female patients with metastatic breast cancer not previously treated for metastatic disease received DOC(60mg/m²)and EPI(60mg/m2)on day 1 every 3 weeks. The patient characteristics included a median age of 53 years. Advanced disease was present in 86% of patients, and recurrent disease was found in 14%; 3 or more metastatic sites had been diagnosed in 38% of patients, and 59% patients were ER+. The median number of courses administered was 6. The median dose intensity was 18. 7mg/m²week for DOC and EPI, and the relative dose intensities were 93. 5%and 93. 3%, respectively. The clinical responses included a complete response in 5%, a partial response in 54%, and stable disease in 33% of patients, with a disease control rate of 92%. The progression-free survival was 78. 3%, and the overall survival was 91. 9% at 1 year. Grade 3/4 toxicities included neutropenia in 82%, leukopenia in 71%, febrile neutropenia in 16%, anorexia in 9%, and anemia in 7%of the patients. Neither congestive heart failure nor toxic death occurred. The D and E combination with doses of 60mg/m2 is an active and generally well-tolerated regimen that can be used as first-line chemotherapy for patients with metastatic breast cancer.
No preview · Article · May 2012 · Gan to kagaku ryoho. Cancer & chemotherapy
[Show abstract][Hide abstract] ABSTRACT: Anthracyclines and taxanes are major cytotoxic drugs against breast cancer. To develop a combination of epirubicin (EPI) and docetaxel (DTX) in Japan, dose escalation and pharmacokinetic studies were performed in patients with advanced or recurrent breast cancer.
Twenty patients received EPI (40, 50 or 60 mg/m(2)) as 5-min intravenous infusion, followed by DTX infusion (50 or 60 mg/m(2)) over 1 h in cohorts of 3-6 patients. The maximum tolerated dose (MTD) was defined during the first cycle when more than 2 of 3 or 3 of 6 patients suffered a dose-limiting toxicity (DLT). The DLT was based on febrile neutropenia (FN), prolonged neutropenia, thrombocytopenia and grade 3-4 nonhematological toxicity during the first cycle. Plasma sampling was performed to assess the pharmacokinetic study of these drugs.
The second level (EPI/DTX 50/50 mg/m(2)) was found to be a maximum tolerated dose because of a short duration of FN with no distress. Subsequently, the protocol was modified to permit a new DLT definition including FN lasting for more than 72 h. At the following levels of EPI/DTX 50/50, 50/60 or 60/60 mg/m(2), the dose escalation study revealed a high incidence of grade 4 neutropenia (100%) and FN (67%), which did not reach DLT. However, the safety committee decided not to go further because of too high an incidence of FN lasting 3 days, although a little less than 72 h. The pharmacokinetic study with a combination of EPI and DTX showed comparable blood levels of DTX and EPI in relation to those seen when given alone.
For further evaluation, the recommended dose and schedule of this combination is EPI 60 mg/m(2) and DTX 60 mg/m(2), given every 3 weeks to patients without prior chemotherapy and EPI 50 mg/m(2) and DTX 50 mg/m(2) given to patients with prior chemotherapy, respectively. The pharmacokinetic study indicates no interaction between EPI and DTX.
[Show abstract][Hide abstract] ABSTRACT: Paclitaxel has been approved for 3-weekly administration in Japan. Recent reports suggest that weekly paclitaxel can achieve a higher tumor response and lower toxicity.
This study was designed to investigate the usefulness and tolerability of weekly paclitaxel by 1-hour infusion in patients with metastatic breast cancer who were previously treated with docetaxel or other anticancer agents.
Thirty-five patients were enrolled. The overall response rate was 41.2% (14/34, 95% confidence interval: 24.6-59.3%). The median time to progression and the median survival time were 218.5 and 624 days, respectively. One patient developed dyspnea, probably induced by a hypersensitivity reaction. The most common hematological toxicities were leukopenia and neutropenia, although no patients developed grade 4 leukopenia or neutropenia and G-CSF support was not required.
Weekly paclitaxel could be safely administered and achieved a relatively high response rate. Weekly paclitaxel would be a good candidate second-line therapy for recurrent or advanced breast cancer.