The clinical impact of a cardiologic follow-up in breast cancer survivors: an observational study.

Anthracycline-containing chemotherapy (A-CHT) can induce late cardiotoxicity adding a considerable burden to cardiovascular risk. Irradiation of left breast cancer has also been associated to an increased risk of cardiovascular disease. The aim of this observational study is to prove the usefulness of an accurate cardiovascular evaluation in left breast cancer survivors treated with radiotherapy (RT) and A-CHT. Patients with left breast cancer, on follow-up after treatment with A-CHT plus RT in an adjuvant setting, were eligible for this observational study. Patients underwent cardiovascular assessment with myocardial perfusion imaging. Thirty patients were enrolled in the study: mean age at diagnosis 55.8 years; stage: I/III; Er and/or pgR status: positive in 24/30 pts; 3 patients in pre-menopausal status. Twenty-two patients (73.3 percent) had normal perfusion imaging, 1 patient (3.3 percent) had a fixed myocardial perfusion defect, 7 patients (23.3 percent) had reversible myocardial perfusion defects; 1 patient (3 percent) with normal perfusion scan showed depressed rest and stress LVEF. Only 1 patient had a large defect and underwent coronary angiography and percutaneous coronary intervention. Five patients with small defect showed normal coronary arteries at Multislice Computed Tomography. Cardiovascular followup may reveal signs of A-CHT or RT-induced cardiotoxicity. A stress test combined with MPI- and GATED-derived data of ventricular systolic performance after stress can give information on the coronary reserve and the contractile reserve and allow early appropriate treatment.

Should we continue to study high-dose chemotherapy in metastatic breast cancer patients? A critical review of the published data.

Data from eight randomised trials on high-dose chemotherapy (HDC) for metastatic breast cancer (MBC) have been published, but only seven studies are evaluable after the Bezwoda trial was discredited. Moreover, overall survival (OS) has been evaluated in only four out of seven studies since three had a crossover design. OS was similar for the HDC and standard-dose chemotherapy (SDC) group in the four evaluable trials, while disease-free survival (DFS) was improved in the HDC group in six of the seven trials. The delay in relapse for patients with metastatic disease represents an important clinical outcome; furthermore, since none of the reported studies randomised more than 220 patients, their statistical power may have been too limited to detect meaningful survival differences. Finally, preliminary experiences have shown that HDC seems to be the ideal platform upon which to build novel therapies. In conclusion, HDC remains an important field of clinical research for breast cancer patients with stage IV disease and, from the studies reported in this article, there is some evidence for offering this therapeutic modality to selected patients who are interested in a medically aggressive approach.

Salvage treatment with epirubicin and/or paclitaxel in metastatic breast cancer patients relapsed after high-dose chemotherapy with peripheral blood progenitor cells.

AIMS AND BACKGROUND: To evaluate feasibility and efficacy of paclitaxel as a single agent or in combination with epirubicin in breast cancer taxane-naive patients who have failed previous high-dose chemotherapy. METHODS: Since February 1995, we have treated 32 patients in first relapse or progression after high-dose chemotherapy. Nineteen patients had metastatic breast cancer, 12 more than 3 involved axillary lymph nodes, and 1 inflammatory breast cancer at inclusion to the program. The median time to relapse after high-dose chemotherapy was 12 months (range, 2-43). At relapse, 12 patients were treated with epirubicin (90 mg/m2) plus paclitaxel (175 mg/m2) administered on day 1 every 21 days. In 20 patients who had previously received more than 350 mg/m2 of a cumulative dose of epirubicin and in one patient pretreated with chemotherapy containing mitoxantrone, we employed paclitaxel (175 mg/m2) alone. A median number of five courses was administered (range, 2-10). RESULTS: The overall response rate after 3 courses (29 of 32 patients were assessable) was 55% and after 6 courses (21 of 32 patients were assessable) was 57%. The median time to progression was 7 months (95% CI, 5.7-9.2), and median survival was 27.5 months (95% CI, 17.8-37.0). Toxicity was recorded for 180 cycles (epirubicin + paclitaxel for 62 cycles and paclitaxel alone for 118 cycles). The main toxicity in both regimens was hematologic. We observed WHO grade 3-4 neutropenia (in 8 patients, 25%), for which G-CSF (5 microg/kg/day s.c.) was employed. WHO grade 3-4 thrombocytopenia occurred in 2 patients (6%) and WHO grade 3 anemia in 1 patient (3%). CONCLUSIONS: Our study showed that paclitaxel (alone or in combination with epirubicin) is feasible as salvage treatment in heavily pretreated patients.

Phase I - II study of oral idarubicin, tegafur and levo-folinate in patients with pretreated advanced breast cancer.

Thirty patients with pretreated advanced breast cancer were enrolled in a study aimed to establish the maximum tolerated dose and to evaluate the efficacy of oral idarubicin (12 mg/m2/day for 3 days every 4 weeks) with tegafur and levo-folinate (200 mg/m2/day and 50 mg/day, respectively, for a minimum of 6 days, increasing the dose and duration according to a modified Fibonacci scheme). The maximum tolerated doses identified were 200 mg/m2 days 1-30 for tegafur and 50 mg days 1-30 for levo-folinate. We obtained 2 partial remissions (7%) and 12 stable disease (45%) in 27 objectively evaluable patients. The main toxicity was gastrointestinal, with no hematologic toxicity. Median time to progression was 4 months (range 2-14), median survival was 10 months (3-30). A median number of 4 cycles (1-13) was administered. The results seem to support the use of this combination in elderly and pretreated patients.

[High-dose chemotherapy of metastatic breast carcinoma]. / Chemioterapia ad alte dosi del carcinoma metastatico della mammella.

PURPOSE: To evaluate efficacy and toxicity of high-dose chemotherapy (HDCT) in metastatic breast cancer (MBC) MATERIALS AND METHODS: A literature search from January 1988 until July 1998 about the treatment of metastatic breast cancer with high dose chemotherapy was conducted. RESULTS: After HDCT the overall response rate was about 80%, with 50% of complete remissions. The median survival was > 18 months. Approximately 20% of the patients experienced long-term progression-free survival. CONCLUSIONS: Although current results appear promising, randomised trials are required to determine the role of HDCT in the treatment of patients with MBC.

[High dose chemotherapy in metastatic carcinoma of the breast]. / Chemioterapia ad alte dosi del carcinoma della mammella metastatico.

PURPOSE: To verify tolerance and clinical efficacy of high-dose chemotherapy (HDCT) in metastatic breast cancer (MBC). PATIENTS AND METHODS: We submitted to HDCT with autologous peripheral blood cells transplant 66 patients, with MBC responding to induction chemotherapy. The condizioning regimen was ICE: iphosphamide 3.3 g/m2 dd. -8/-6, carboplatin 450 mg/m2 plus etoposide 400 mg/m2 dd. -5/-3 (21 patients = 78%); CTM: cyclophosphamide 100 mg/kg dd. -4/-3, tyothepa 500 mg:m2 d.-5, mytoxantrone 40 mg/m2 d. -6 (6 patients, 22%). RESULTS: Median number of aphereses was 2 (range 1-5), median amount of CD34+ cells/kg bw of 10 x 10E6 (range 3.5-38.2). Median recovery time was 10th day for PMN (range 8-37) while for platelets it was 9th day (range 8-37): total hospital stay was of 24 days (range 22-48). After induction therapy we had PR in 13/27 metastatic patients (48%) and CR in 14/27 (52%). After conditioning treatment we had PR in 12/27 (44%) and CR in 15/27 (56%). Median time to progression was 19 months (range 7-38) and median survival 52 months (range 7-59+), with 30% surviving beyond 4 years. CONCLUSIONS: Feasibility of HDCT in advanced breast cancer seems verified. The promising results need to be confirmed.