Doxorubicin-based chemotherapy in elderly patients with metastatic breast cancer. Tolerance and outcome

BACKGROUND: Metastatic breast cancer in elderly patients is less often treated with chemotherapy than in younger patients because of concerns related to toxic effects and tolerance. This is especially the case with doxorubicin-containing regimens. METHODS: We conducted a retrospective study of 1011 consecutive patients with metastatic breast cancer treated with doxorubicin-based chemotherapy protocols between July 1973 and July 1984. Age was not an exclusion criterion. Patient characteristics, dose intensity, hematologic-related toxic effects, and the cause of death were analyzed. The Kaplan-Meier survival curves were plotted and tested by the generalized Wilcoxon test. RESULTS: Seven hundred sixty-seven patients aged between 50 and 64 years were identified. While the response rate was higher in the younger group, the overall survival curves were similar for the two groups (P = .06), as well as the time to progression of the disease (P = .15). The dose intensity was comparable between the groups (P = .49), as was the median platelet and white blood cell nadirs. Neutropenic fever occurred in 16% of each group (P = 83), and fever in 12% and 17% of each group, respectively (P = .05). Death from infections occurred in 3.1% and 3.2% of patients in the two groups, respectively (P = .82). CONCLUSION: Patients with metastatic breast carcinoma who are older than 65 years tolerate the acute side effects of doxorubicin-based combination chemotherapy as well as the younger age group. Time to progression of disease and the overall survival are similar for both groups. Doxorubicin-based regimens are safe and effective for patients older than 65 years.     

Use of a 24-kilodalton Trypanosoma cruzi recombinant protein to monitor cure of human Chagas' disease

A 24-kDa recombinant protein from Trypanosoma cruzi (rTc24) was evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blot (immunoblot) tests to identify treated chagasic patients considered parasitologically cured on the basis of persistently negative tests of hemocultures and lytic antibodies. Some of these patients were termed dissociated because their sera, although negative by the complement-mediated lysis test, were positive by conventional serology. The negative lysis test indicates the absence of active infection after specific treatment, but this assay requires live and infectious parasites and cannot be used easily in a laboratory routine. Here we tested rTc24 by ELISA and Western blotting as an alternative for the complement-mediated lysis test. For the group of patients with active infection despite the treatment (uncured patients), all the sera tested recognized rTc24 in both tests. For the dissociated patients, approximately 80% of the sera did not react with rTc24 in the ELISA or in Western blots, in agreement with the negative complement-mediated lysis tests. Thus, the 24-kDa T. cruzi recombinant antigen, when used for initial trials to evaluate cure of chagasic patients submitted to specific treatment, will allow the identification of most, but not all, cases.     

Residual metastatic axillary lymph nodes following neoadjuvant chemotherapy predict disease-free survival in patients with locally advanced breast cancer

BACKGROUND: This study was performed to validate the prognostic significance of residual axillary lymph node metastases in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy and to analyze other clinicopathologic factors that might be independent predictors of disease-free survival (DFS) in an attempt to identify patients in whom axillary dissection might be omitted. METHODS: One hundred sixty-five assessable patients with LABC were treated in a prospective trial of neoadjuvant chemotherapy utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Responding patients were treated with segmental mastectomy and axillary dissection or modified radical mastectomy. Patients subsequently received additional chemotherapy followed by irradiation of the breast or chest wall and draining lymphatics. The median follow-up was 35 months. RESULTS: Clinical tumor response to neoadjuvant chemotherapy (P = 0.046) and the number of residual metastatic axillary lymph nodes found at axillary dissection (P = 0.05) were the only independent predictors of DFS. Patients with a complete clinical response had a predictably excellent DFS and those with no change or progressive disease had a poor DFS. In patients with a partial response, the number of residual metastatic lymph nodes further stratified patients with respect to DFS (P = 0.006). CONCLUSIONS: Clinical response and residual metastatic axillary lymph nodes following neoadjuvant chemotherapy are important predictors of DFS. Patients with a clinically positive axilla following neoadjuvant chemotherapy should undergo axillary dissection to ensure local control. However, the benefit of axillary dissection in patients with a clinically negative axilla may be minimal if the axilla will be irradiated, and histologic staging does not affect subsequent systemic treatment. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following neoadjuvant chemotherapy is presently under way to evaluate this hypothesis.