Adjuvant therapy with edrecolomab versus observation in stage II colon cancer: a multicenter randomized phase III study.

BACKGROUND: In a phase III study recruiting patients with stage II colon cancer the effect of adjuvant therapy with edrecolomab, a murine monoclonal antibody to the cell-surface glycoprotein 17-1A, was compared to observation alone. PATIENTS AND METHODS: From January 1997 until July 2000 a total of 377 patients were postoperatively stratified according to tumor stage (T3 vs. T4) and center, and randomly allocated to either treatment with edrecolomab (cohort A, n = 183) or observation (cohort B, n = 194). Patients in cohort A received a total of 900 mg edrecolomab. The study was terminated prematurely because of discontinuation of drug supply in Germany. RESULTS: 305 patients were eligible for the primary endpoint of overall survival and 282 patients for disease-free survival. After a median follow-up of 42 months overall survival and disease-free survival were not significantly different. Toxicity was mild. CONCLUSIONS: In the present study, postoperative adjuvant treatment with edrecolomab in patients with resected stage II colon cancer did not improve overall or disease-free survival.

[Occlusion of central venous port catheters after simultaneous 24 h infusions of 5-FU and calcium-folinic acid in patients with gastrointestinal cancer]. / Hohe Verschlussrate von zentralen Venenkathetersystemen durch Calcit-Präzipitate unter 24 h-Mischinfusion aus 5-Fluorouracil und Calciumfolinat bei Patienten mit gastrointestinalen Tumoren.

Folinic acid-modulated 5-FU regimens are standard elements in several chemotherapy combinations like FOLFIRI, FOLFOX or AIO-regimen in the palliative treatment of patients with gastrointestinal cancer. When the simultaneous mixed infusion of 5-FU and calcium-folinic acid (Leucovorin) was authorized by the BfArM in 2002, we introduced this application regimen in the treatment of our cancer patients. 19 patients (AIO-regimen [5], FOLFIRI [12] and FOLFOX [2]) received a simultaneously mixed infusion of calcium-folinic acid and 5-FU over 24 hours with a total of 110 applications. 5-FU doses varied between 2000 and 2600 mg/m2, calcium-folinic acid was given with 500 mg/m2, infusion rate was 10 ml/hour using a 24 h pump. Central venous catheters employed included single Barth-Port in 18 cases, 1 patient had a Viggon-Port. In 3 out of the 19 patients catheter occlusion was noticed after 8-10 weekly applications of the mixed infusion. Heparine and subsequently urokinase were not successful in reversing the obstruction. All three catheters had to be explanted. Catheter tips in all cases showed a yellow cristalline precipitation. The crystallographic analysis exhibited calcium carbonate (CaCO3) in its polymorphic form (calcite). Thus, we confirmed calcite formation causing catheter occlusion as a frequent complication during a continuous 24 h-infusion of mixed high dose 5-FU and calcium-folinic acid. This reaction could not be avoided by increasing infusion volume and the application flow rate. As a result of our findings, recommending using calcium-folinic acid mixed with 5-FU has been withdrawn in the meantime.

Safety and cost effectiveness of a 10 x 10(9)/L trigger for prophylactic platelet transfusions compared with the traditional 20 x 10(9)/L trigger: a prospective comparative trial in 105 patients with acute myeloid leukemia.

In 105 consecutive patients with de novo acute myeloid leukemia (French-American-British M3 excluded), we compared prospectively the risk of bleeding complications, the number of platelet and red blood cell transfusions administered, and the costs of transfusions using two different prophylactic platelet transfusion protocols. Two hundred sixteen cycles of induction or consolidation chemotherapy and 3,843 days of thrombocytopenia less than 25 x 10(9)/L were evaluated. At the start of the study, each of the 17 participating centers decided whether they would use a 10 x 10(9)/L prophylactic platelet transfusion trigger (group A/8 centers) or a 20 x 10(9)/L trigger (group B/9 centers). Bleeding complications (World Health Organization grade 2-4) during treatment cycles were comparable in the two groups: 20 of 110 (18%) in group A and 18 of 106 (17%) in group B (P = .8). Serious bleeding events (grade 3-4) were generally not related to the patient's platelet count but were the consequence of local lesions and plasma coagulation factor deficiencies due to sepsis. Eighty-six percent of the serious bleeding episodes occurred during induction chemotherapy. No patient died of a bleeding complication. There were no significant differences in the number of red blood cell transfusions administered between the two groups, but there were significant differences in the number of platelet transfusions administered per treatment cycle: pooled random donor platelet concentrates averaged 15.4 versus 25.4 (P < .01) and apheresis platelets averaged 3.0 versus 4.8 (P < .05) for group A versus group B, respectively. This resulted in the cost of platelet therapy being one third lower in group A compared with group B without any associated increase in bleeding risk.

[Intensive post-remission therapy in acute myeloid leukemia. Results of a prospective comparative study by the South Germany Hemoblastosis Group]. / Intensive Postremissionstherapie bei akuter myeloischer Leukämie. Ergebnisse einer prospektiv vergleichenden Studie der Süddeutschen Hmoblastosegruppe (SHG).

BACKGROUND: To study intensive postremission therapy in adult patients with acute myeloid leukemia myeloablative therapy followed by allogeneic or unpurged autologous bone marrow transplantation (BMT) was compared with high-dose cytosine-arabinoside/daunorubicin (HDAC) consolidation. PATIENTS AND METHODS: 148 de novo AML patients of maximum 50 years (median 36 years, range 16 to 50) were enrolled in the trial. Following induction and early consolidation chemotherapy consisting of daunorubicin, cytosine-arabinoside and VP-16 (DAV), patients with an HLA-identical sibling underwent allogeneic BMT. The other patients received (by randomization or patient's decision) either HDAC or high-dose busulfan plus cyclophosphamide followed by autologous BMT. RESULTS: Hundred and five 105 (70.9%) patients achieved a complete remission. The event-free survival rates after intensive postremission therapy after 72 months were: after BMT (24 patients) 62% (95% confidence interval +/- 19%), after HDAC (44 patients) 36 +/- 16% and after autologous BMT (12 patients) 18 +/- 22%. Thus allogeneic BMT was superior to autologous BMT (p = 0.04), as was HDAC compared to autologous BMT, although not significantly so (p = 0.15). Patients receiving 2 cycles of HDAC had a better 6-year event-free survival rate (47%) and a lower relapse rate (50%) than patients who received only 1 course (29% and 70% respectively). CONCLUSIONS: High-dose busulfan/cyclophosphamide followed by unpurged autologous BMT early after achieving CR had no advantage over high-dose ara-c/daunorubicin. Two cycles of HDAC yielded better results than 1 cycle. The highest event-free survival rate was reached with myeloablative therapy followed by allogeneic BMT.

Reduction of metastatic carcinoma cells in bone marrow by intravenously administered monoclonal antibody: towards a novel surrogate test to monitor adjuvant therapies of solid tumours.

In a pilot, prospective randomised study, 40 patients with breast and colorectal cancer presenting with metastatic cytokeratin (CK)-positive tumour cells in bone marrow were treated either with six doses of 100 mg of a monoclonal Lewis Y antibody during 2 weeks or with a placebo regimen, consisting of six infusions of human serum albumin (HSA). CK-positive cells in marrow were monitored prior to and on days 15 and 60 after commencement of treatment. In 30 patients presenting with relatively low tumour cell numbers (1-11 per 4 x 10(5) bone marrow cells), a therapy-induced reduction of CK-positive cells could not be conclusively determined. More meaningful quantitative data were obtained in 10 breast cancer patients presenting with more than 20 tumour cells per 4 x 10(5) nucleated bone marrow cells. 7 of these patients had been randomised to the antibody arm, and 5 showed an eradication or a distinct reduction of CK-positive/Lewis Y-positive cells of at least one log unit, while 2 patients, presenting with Lewis Y-negative tumour cells, showed no corresponding decrease. Similarly, in all 3 patients randomised to the placebo arm, tumour cells were not reduced. Because the antibody exerted a marked cytotoxicity on tumour cell lines when tested ex vivo in serum taken from these patients after antibody infusion, we postulate that the observed, prompt reduction of individual tumour cells in bone marrow was due to the cytotoxic action of the injected antibody. Although monitoring micrometastatic cells in bone marrow of patients with high tumour cell counts appears to be feasible, the immunocytochemical assay needs to be improved for patients with lower cell numbers before it can be applied as a surrogate test for adjuvant therapies.