Epirubicin and docetaxel as neoadjuvant treatment of locally advanced breast cancer: a phase II study.

AIMS AND BACKGROUND: Neoadjuvant chemotherapy is the standard treatment for locally advanced breast cancer. The combination of anthracyclines and taxanes is considered the first choice chemotherapy in advanced breast cancer. We report here the overall results of a phase II study of epirubicin and docetaxel as neoadjuvant chemotherapy in advanced breast cancer. PATIENTS AND METHODS: Forty-five patients with locally advanced, nonmetastatic breast carcinoma were treated with epirubicin, 90 mg/m2, docetaxel, 75 mg/m2, intravenously, every 3 weeks for 4 cycles before and 4 cycles after surgery, followed by tamoxifen for 5 years if estrogen receptor positive and radiation therapy if indicated. Patient characteristics included a median age of 45 years; pre Ipostmenopausal, 311/14 patients; T3-T4 in 33, N0/N1 in 12/33; ductal/lobular in 42/3; ER+ in 23; and HER2 overexpression in 23. RESULTS: Clinical response included complete remission in 7 patients and partial remission in 27 (response rate, 75%). All 45 patients underwent surgery (quadrantectomy in 7). Histological examination of the breast and lymph nodes revealed no signs of disease in 3 patients and ductal carcinoma in situ only in 2. Twenty-five patients completed the chemotherapy program. G3-G4 toxicity included neutropenia in 39 patients. No other G3-4 toxicity nor toxic deaths occurred. Median relapse-free and overall survival were 35 and 56 months, respectively. CONCLUSIONS: The neoadjuvant treatment was active and well tolerated, but the incidence of pathologic complete remissions was relatively low.

Long-term, weekly one-hour infusion of paclitaxel in patients with metastatic breast cancer: a phase II monoinstitutional study.

AIMS AND BACKGROUND: A dose-dense therapy with weekly paclitaxel given as a 1-hr infusion yielded a 53% overall response rate in breast cancer patients resistant to anthracyclines, with a remarkable lack of neutropenia (Seidman, 1998). We performed a monoinstitutional phase II trial in order to confirm these interesting results. PATIENTS AND METHODS: Eligibility criteria included advanced breast cancer and no taxane pretreatment. Paclitaxel was administered weekly at the dose of 90 mg/m2 (60 mg/m2 in patients at high risk of toxicity) by 1-hr i.v. infusion. Fifty-eight patients entered the trial. Median age was 54 years (range, 38-72). Performance status was good (median 1; range, 0-2). Fifty-two patients were pretreated with anthracyclines. RESULTS: A total of 1,004 weekly paclitaxel infusions were administered (median, 19 per patient; range, 4-43). The median delivered dose intensity was 67.4 mg/m2/week (range, 43-86). Twenty-eight of the 58 assessable patients obtained an objective response (48%), 15 had stable disease (26%) and 15 progressed (26%). The overall response rate was 48% (95% confidence interval, 35-61%) with 5 complete responses (8%). In anthracycline-pretreated patients, 23/52 (44%) responses were observed. Median duration of response was 5 months (range, 3-27). Toxicity was acceptable apart from a case of pulmonary embolism in a 70-year-old patient, 1 case of congestive heart failure in an anthracycline-pretreated patient aged 64, and 9 cases of G3 neutropenia. Peripheral neuropathy was observed in 38 patients (64%), usually of a mild grade; alopecia in 45 patients (78%) and onychopathy in 16 (28%), usually of a mild grade apart from 2 cases requiring treatment interruption. Tachycardia and atrial fibrillation occurred in a 55-year-old woman. CONCLUSIONS: Our data seem to confirm the activity and safety of this approach even in a heavily pretreated population of patients. Its combination with other active drugs needs to be further investigated in clinical trials.

Acceptance of external infusion pumps in patients with advanced breast cancer receiving continuous infusion fluorouracil.

BACKGROUND: We investigated the physical and psychological adaptation to a protracted continuous infusion system in a series of patients receiving protracted continuous infusion of 5-fluorouracil for advanced breast cancer. PATIENTS AND METHODS: The protracted continuous infusion of 5-fluorouracil was administered by means of a portable elastomeric pump (Baxter Seven-Day Infusor, 0.5 mL/hr) via an indwelling Groshong catheter. Patients were asked to complete a questionnaire exploring the impact of the continuous infusion system upon various aspects of daily life, the overall level of disturbance, the general judgement on its quality, and their willingness to resume the same kind of treatment in the future. All items were graded on a 4-point scale from 0 = not at all, to 4 = very much. RESULTS: Seventy-one patients were evaluated. All patients received 5-fluorouracil at the dose of 250 mg/m2/day as a protracted continuous infusion alone (n = 14) or in combination with vinorelbine (n = 45) or Taxol (n = 12). The median duration of the protracted continuous infusion before evaluation was 9 months (3-31). The mean level of disturbance to daily activities was 0.86 points. The activities most frequently disturbed by treatment included daily personal care (mean, 1.76 points) and sexual activity (mean, 1.20 points). Twenty-one patients required medical intervention because of problems related to the protracted continuous infusion system. The overall level of disturbance was rated at a mean level of 0.72 points, whereas the overall merits of the protracted continuous infusion system and the willingness of the patient to resume protracted continuous infusion in the future were rated at a mean level of 2.90 and 2.55 points, respectively. CONCLUSIONS: The system for the protracted continuous infusion of 5-fluorouracil was well tolerated by the patients, who were able in most cases to perform their daily activities with little or no disturbance, needing only occasional help, and were willing to resume the same treatment modality if necessary.

Breast cancer and pregnancy.

The diagnosis of breast cancer during pregnancy is a rare event, but the young age of the patient together with the emotional impact for both the family and the doctors make therapeutic choices usually very difficult. Until recently, the occurrence of pregnancy associated breast cancer was thought to hold a grave prognosis and therapeutic abortion was very often advised in common practice. The hormonal environment with the increase in estrogens and progesterone was the main factor for the fear of tumor stimulation. The course of breast cancer, however, does not appear to be adversely affected by continuation of pregnancy. In the last years it was realized that potentially curative therapies can be administered even when pregnancy is continued. Of course in the medical literature there is no randomized clinical trial helping in taking decision in this setting; however, a significant experience already exists in some institutions and can guide management in these difficult cases. The aim of our review is to give an answer to questions usually coming from various specialists who collaborate with the oncologists in treating these patients and furthermore to try and find some basic guidelines which can be used in the information of the patients regarding previous experience in this field. The problem of a pregnancy after treatment for breast cancer is also analyzed, as this aspect is an emerging issue in clinical oncology. The decision should be evaluated for each single patient, taking into account the prognosis of the patient and her desire of pregnancy.