Preoperative treatment with capecitabine, cetuximab and radiotherapy for primary locally advanced rectal cancer--a phase II clinical trial.

BACKGROUND/AIM: To investigate the feasibility and safety of preoperative capecitabine, cetuximab and radiation in patients with MRI-defined locally advanced rectal cancer (LARC, cT3/T4). PATIENTS AND METHODS: 31 patients with LARC were treated with cetuximab and capecitabine concomitantly with 45 Gy radiotherapy and resected by total mesorectal excision. Histopathological response and association with KRAS status was evaluated. RESULTS: R0-resection was possible in 27 of 31 (86%) patients. No complete pathological remission was observed. Radiochemotherapy with capecitabine and cetuximab was safe to administer and diarrhea was the main toxicity. KRAS-status did not correlate to down-staging or pathological response concerning T- or N-stage. CONCLUSION: Neoadjuvant therapy with capecitabine and cetuximab in combination with radiotherapy did not lead to complete pathological remission. Treatment tolerability was excellent and toxicity remained low. KRAS status did not influence treatment outcomes. Capecitabine in combination with radiotherapy remains a standard therapy for locally advanced rectal cancer.

The potential risk of neoadjuvant chemotherapy in breast cancer patients--results from a prospective randomized trial of the Austrian Breast and Colorectal Cancer Study Group (ABCSG-07).

PURPOSE: To evaluate the impact that pre- and postoperatively administered chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF) and postoperative chemotherapy vs. postoperative chemotherapy alone have on long-term prognosis. PATIENTS AND METHODS: The ABCSG conducted a nationwide randomized phase III trial in high-risk endocrine non-responsive breast cancer patients comparing pre- and postoperative chemotherapy containing CMF as preoperative treatment vs. postoperative chemotherapy alone between 1991 and 1999. From 1996 the ABCSG-07 protocol was amended to also allow randomization of high-risk endocrine-responsive patients. Of 423 eligible patients with high-risk primary breast cancer, 203 patients were randomly assigned to preoperatively receive three cycles of CMF (cyclophosphamide, methotrexate, fluorouracil; 600/40/600 mg/m(2)) intravenously on day 1 and 8, while 195 patients received postoperative chemotherapy alone. In both groups, three cycles of CMF were given initially, and another three cycles of CMF were administered in node-negative patients, whereas node-positive patients received three cycles of EC (epirubicin, cyclophosphamide; 70/600 mg/m(2)). RESULTS: Overall response rate to preoperative chemotherapy with three cycles of CMF was 56.2%; complete pathological response was achieved in 12 patients (5.9%). Recurrence-free survival was significantly better in patients receiving chemotherapy postoperatively (HR 0.7, 0.515-0.955; P = 0.024). No survival difference was observed between the two therapy groups (HR 0.800, 0.563-1.136; P = 0.213). DISCUSSION: Preoperative chemotherapy with CMF has to be considered as insufficient in high-risk breast cancer patients. Delayed surgery and anthracycline-based chemotherapy result in shorter recurrence-free survival but not overall survival.

Impact of blood transfusions on recurrence and survival after rectal cancer surgery.

PURPOSE: This study was designed to determine whether type or number of blood units transfused affected short-term and long-term outcome in patients undergoing surgery for rectal cancer. The number of perioperative blood units is associated with postoperative mortality and overall survival by some authors. In addition, allogenic perioperative blood transfusion has been postulated to produce host immunosuppression and has been reported to result in adverse outcome in patients with colorectal cancer. Autologous blood transfusion might improve results compared with allogenic transfusion. METHODS: Clinical outcome for 597 patients undergoing surgery for rectal cancer was analyzed according to their transfusion status. Results for type (autologous or allogenic) and number of blood units transfused were recorded. RESULTS: Blood transfusion was associated with increased postoperative mortality at 60 days. Patients who received > 3 units had a postoperative mortality of 6 percent compared with 1 percent for patients who received 1 to 3 units and 0 percent for patients who did not require transfusions. No difference was found between patients who received autologous or allogenic blood. Blood transfusions were also associated with impaired overall survival in a univariate analysis, but this finding was not confirmed in the multivariate analysis. The number or type of blood units transfused did not influence oncologic results. Local recurrence rates, distant metastases rates, and disease-free survival were not influenced by transfusion in our patients. CONCLUSIONS: Increased numbers of blood units were associated with postoperative mortality. However, there is no reason, with respect to cancer recurrence or disease-free survival, to use a program of transfusion with autologous blood in patients undergoing surgery for rectal cancer.