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Notes: Summary The diagnostic validity of serial CEA determinations in metastatic breast cancer was investigated. First, the CEA values within 8 weeks after start of therapy were correlated with the response to therapy. Second, the CEA levels were used to predict progression after remission or stable disease. These investigations were performed in 150 patients with advanced breast cancer who had clinical follow-ups and serial CEA determinations every one to three months. CEA was not useful for monitoring response to therapy (sensitivity 63%, specifity 58%) or prediction of relapse (sensitivity 61%, specifity 82%) if CEA levels were correlated with clinical course in all patients. However, diagnostic validity of CEA was achieved if the patients were selected and appropriate definitions of significant changes in CEA used. Thus, 83% of the responders (sensitivity) could be identified by a significant decrease of CEA titers in patients with CEA levels of ≧10 ng/ml. A decrease of more than 10% of pretreatment levels during the first 4–8 weeks after start of therapy proved to be the appropriate definition of a significant decrease of CEA titers. However, 32% of the non-responders were misclassified as responders (unspecifity) using these criteria. The positive predictive value of a significant decrease of CEA for response to therapy was 72% (prevalence 45%), the negative predictive value 82% (prevalence 55%). Rising CEA titers specifically predicted progression of disease in patients with remission or stable disease. However, an appropriate sensitivity (86%) was achieved only in patients with baseline CEA levels of ≧5 ng/ml. The selection criteria described applied to one-third of the patients in the present study. Prospective studies based on these results have to show whether the definitions used can be generalized and are to be recommended for clinical practice.

Notes: Abstract Purpose: The current study was initiated to assess the clinical efficacy and side effects of rituximab in patients with relapsed advanced stage follicular lymphoma. Patients and methods: The study was performed as an open-label non-randomized multicenter phase-II trial and included patients older than 18 years of age with relapsed advanced-stage follicular lymphomas (FL) grades I and II, according to the REAL classification, or with centroblastic/centrocytic (CB/CC lymphomas according to the Kiel classification. Four weekly doses of 375 mg/m2 rituximab were applied. Results: 38 patients from eight centers were included between January 1997 and January 1998 and were evaluable for response and toxicity on an intention to treat basis. The median age was 55 years (range 26–75 years). Thirteen patients (35%) were in first relapse, 11 patients (30%) in second, and 13 patients (35%) in third relapse. The median time between primary diagnosis and study entry was 4.6 years (range 0.9–14.7 years). Twenty-three patients tolerated the application of rituximab without adverse events; in 13 cases the infusion rate had to be reduced because of side effects; in two patients the application was stopped because of pharyngeal edema and anaphylactoid reaction. The most frequent side effects were fever (13 patients) and rigor (13 patients); 65% of the side effects were observed after the first infusion. Twenty grade-III/IV side effects were considered to be related to treatment: lymphocytopenia (3), granalocytopenia (1), thrombocytopenia (2), fever (1), hyperglycermia (1), venous thrombosis (1), syncope (1), plasmatic coagulation disorder (1), shortness of breath (2), photosensitivity (1), cardiac failure (1), chills (1), sepsis (1), tumor lysis (1), anemia (1), and pharyngeal edema (1). Eight patients were not eligible for assessment of response because of non-follicular subtypes of low-grade lymphomas (n=6) or early termination of therapy at the first infusion because of severe side effects (n=2). From the 30 evaluable cases with follicular lymphomas, five patients achieved a complete remission (CR) (17%), nine patients a partial remission (PR) (30%), and two patients a minor response (MR) (7%). The overall response rate was 47%. The median time to treatment progression (TTP) was 201 days (range 64–293 days), with five patients experiencing long-lasting remissions of 214–293 days duration. In three patients, the rituximab-induced remission exceeded the preceding progression-free interval substantially. Bulky disease (P=0.058) and/or bone-marrow involvement (P=0.046) were associated with poor response. Conclusion: This study confirms the moderate treatment-related toxicity and the high antilymphoma activity of rituximab in patients with relapsed follicular lymphoma. Further studies are needed to determine the role of rituximab in the first-line treatment of these disorders and its combination with conventional chemotherapy.

Notes: Summary The capability of breast cancer to secrete CEA might have biological significance. In 105 patients with metastatic breast cancer serial CEA determinations and clinical follow-up data were available during progression of disease up to death. In this series, 39 patients (37%) had constantly low CEA levels (〈10 ng/ml), whereas 66 patients (63%) showed CEA values exceeding 10 ng/ml with progression. The patients with low CEA levels had significantly shorter median survival times (P=0.001) after mastectomy (39 versus 65 months) and after recurrence (18 versus 28 months) than the patients with high CEA levels. This difference was due first to a poor-risk group of 13 patients with rapidly disseminating tumors, very short survival (〈12 months), and low CEA levels. Secondly, there were more patients with pulmonary involvement and unfavorable prognosis and fewer patients with osseous metastases and long survival in the low-CEA group. In conclusion, there might be a subtype of breast cancer with rapid progression and low CEA secretion. This clinical observation has to be confirmed by histological grading and CEA staining of these tumors.