S. Pastorino

Effect of adjuvant chemotherapy with or without anthracyclines on the activity and efficacy of first-line cyclophosphamide, epidoxorubicin, and fluorouracil in patients with metastatic breast cancer.

PURPOSE To evaluate the effect of previous adjuvant chemotherapy with or without anthracyclines on overall survival (OS), progression-free survival (PFS), and objective response (OR) rates of metastatic breast cancer patients treated with cyclophosphamide, epidoxorubicin, and fluorouracil (CEF) as first-line chemotherapy. PATIENTS AND METHODS Three-hundred twenty-six assessable metastatic breast cancer patients entered onto four consecutive randomized trials performed in our Institution and North-West Oncology Group (GONO) cooperative centers from 1983 to 1994. Patients received CEF-based chemotherapy as first-line therapy and were then evaluated. One hundred forty-four patients (44%) did not receive previous adjuvant chemotherapy, and 143 (44%) and 39 (12%) patients received cyclophosphamide, methotrexate, and fluorouracil (CMF)-based and anthracycline-based adjuvant chemotherapy, respectively. RESULTS ORs to CEF chemotherapy were observed in 161 patients (49.4%). On univariate analysis, patients who had received prior adjuvant chemotherapy had a significantly lower probability of response than patients who did not: 43% versus 58% (P=.02). No difference between CMF-based (OR rate, 43%) and anthracycline-based (OR rate, 44%) adjuvant chemotherapy was observed. Stepwise logistic regression analysis indicated that adjuvant chemotherapy (P=.005), bone as dominant metastatic site (P=.02), and previous hormonotherapy for metastatic disease (P=.005) were the most important factors in predicting a poor OR rate. The median PFS and OS times of the whole group were 9.8 and 17.9 months, respectively. Patients who did not receive adjuvant chemotherapy had a longer survival time (21.1 months) compared with patients previously treated with CMF-based (15.3 months) or anthracycline-based (15.8 months) adjuvant chemotherapy. Multivariate analysis confirmed adjuvant chemotherapy to be among the strongest prognostic factors associated with both a poor PFS and OS. CONCLUSION Previous adjuvant chemotherapy adversely affects OR, PFS, and OS in metastatic breast cancer patients treated with the CEF regimen as first-line chemotherapy. No difference was observed between patients previously treated with CMF-based or anthracycline-based adjuvant chemotherapy.

Efficacy of Normal Saline Versus Heparinized Saline Solution for Locking Catheters of Totally Implantable Long-Term Central Vascular Access Devices in Adult Cancer Patients

Background:Heparin solution is routinely used to maintain the patency of infusion devices. Literature supports the alternative use of normal saline solution for flushing and locking intravenous infusion devices especially for pediatric patients. There is uncertainty regarding safety and efficacy of this policy for intermittent locking of implanted ports. Objective:This study evaluates efficacy and safety of normal saline solution for intermittent locking procedures of implanted ports. Methods:This is a retrospective observational cohort study of 610 implanted ports receiving 2 different locking solutions conducted at the National Institute for Cancer Research, IST Genova, Italy, from January 2007 to August 2009. Group A (n = 297) received heparinized solution (10 mL/500 U heparin), whereas group B (n = 313), 10 mL normal saline. Primary endpoint was irreversible port occlusion. Minimum follow-up was 12 months. The role of age, type of tumor, disease stage, access site, access body side, catheter tip position, and concomitant use of parenteral nutrition and chemotherapy was evaluated in secondary aim. Results:Results fail to show statistically significant differences in implanted ports survival free from failure for occlusive events between the use of heparinized solution and that of normal saline for the maintenance of port patency, both in univariate (P = .9) and in multivariate analyses (P = .7). Conclusion:Normal saline solution seems to be as effective as heparinized solution for keeping patent implanted ports in adult cancer patients. Implications for Practice:Switching from heparinized solution to normal saline for catheter intermittent lock of ports seems a safe procedure.

Concurrent vs Sequential Adjuvant Chemotherapy and Hormone Therapy in Breast Cancer: A Multicenter Randomized Phase III Trial

BACKGROUND The most appropriate timing of chemotherapy and hormone therapy administration is a critical issue in early breast cancer patients. The purpose of our study was to compare the efficacy of concurrent vs sequential administration of adjuvant chemotherapy and tamoxifen. METHODS Women with node-positive primary breast cancer were randomly assigned to receive tamoxifen (20 mg/d for 5 years) during (concurrent arm) or after (sequential arm) adjuvant chemotherapy. Chemotherapy consisted of alternating regimens of cyclophosphamide, epidoxorubicin, and 5-fluorouracil and cyclophosphamide, methotrexate, and 5-fluorouracil every 21 days for a total of 12 cycles. The primary endpoint was overall survival (OS), and secondary endpoints were toxic effects and disease-free survival (DFS). No provision for interim analyses was made in the original study protocol. Survival curves were estimated by the Kaplan-Meier method. Multivariable Cox regression models, adjusted for age, menopausal status, tumor stage, and lymph node and hormone receptor status, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS From 1985 to 1992, 431 patients were randomly assigned and studied according to the intention-to-treat principle. After a maximum of 15.4 years of follow-up (median 12.3 years), the estimated actuarial 10-year OS was equivalent for the two study arms (concurrent arm: 111 patients, 66%, 95% CI = 59% to 72%; sequential arm: 114 patients, 65%, 95% CI = 59% to 72%, P = .86). No differences in DFS and toxic effects were evident. Four interim analyses were performed, but no alpha error adjustment was necessary because of the largely negative results of this final analysis (sequential vs concurrent arm: HR of death = 1.06, 95% CI = 0.78 to 1.44, P = .76; HR of relapse = 1.16, 95% CI = 0.88 to 1.52, P = .36). CONCLUSIONS No statistically significant differences in OS, DFS, and toxic effects between concurrent and sequential adjuvant chemo- and hormone therapies were observed. Our study does not support the superiority of one schedule of chemo- and hormone-therapy administration over the other. However, because of the limited statistical power of the study, these results must be considered with caution.

Analysis and clinical relevance of human leukocyte antigen class I, heavy chain, and β2-microglobulin downregulation in breast cancer

Investigation is lacking regarding the clinical impact of human leukocyte antigen (HLA) class I downregulation in breast cancer and results are inconsistent. In this study, we investigated the expression of HLA class I, the heavy chain, and beta2-microglobulin (beta2-m) by immunohistochemistry in 67 breast carcinomas (BC) and correlated results with clinical-pathologic parameters and patient outcomes. Seventy-six percent of BC were downregulated for HLA class I, whereas downregulation of heavy chain and beta2-m was observed in 57 and 46% of BC, respectively. A significant association existed between the absence of tumor necrosis and downregulation of class I and beta2-m and between the absence of lymphovascular invasion and patients age and downregulated class I and heavy chain, respectively. Among the lymph node-positive BC patients, a significantly improved overall survival was observed in those showing beta2-m downregulation compared with patients with normal beta2-m. This result may correlate with the role of beta2-m in regulating cancer cell growth.