c-erbB-2 in serum of patients receiving fractionated paclitaxel chemotherapy.
Humanized anti-c-erbB-2 antibodies (Herceptin) in a weekly schedule are a new therapeutic option for the treatment of c-erbB-2-positive, advanced breast cancer (ABC). Addition of Herceptin to first-line chemotherapy for c-erbB-2 overexpressing ABC increased anticancer activity in a randomized phase III trial. However, except from standard UICC response criteria, there are hitherto no recommendations as to how to monitor Herceptin therapy. In a therapy optimizing study with weekly dose-intensified paclitaxel monotherapy (schedule: 90 mg/m2 weekly x 6, q9w), we correlated the clinical course of stage IV breast cancer in UICC criteria with the course of the shed c-erbB-2 protein fragment and the CA 27.29 serum level. Serum samples were taken weekly from 35 patients to measure the serum c-erbB-2 and CA 27.29 protein levels over time. Up to now, 10 patients (28.5%) are c-erbB-2 positive (> 15 U/mL), with a median baseline protein expression of 65 U/mL. While the overall response rate in the study is 36%, the response rate among c-erbB-2-positive patients is 62%, indicating a high sensitivity of c-erbB-2 positive patients to dose-intense paclitaxel treatment. In all responders the c-erbB-2 serum level decreased below the detection limit either before the clinical diagnosis of response or by the end of the next cycle. However, the normalization of the c-erbB-2 serum level was not specific for responders as patients with stable or progressive disease presented normalized levels or a > 50% decrease of the baseline level, too. The courses of the c-erbB-2 protein levels correlated closely with the courses of CA 27.29. The decrease in the serum c-erbB-2 oncoprotein level might indicate a regression of c-erbB-2 positive tumor load. This may even happen in progressive disease according to UICC criteria when the c-erbB-2-negative tumor fraction progresses while the c-erbB-2-positive fraction is controlled. Another explanation would be that the mechanisms of c-erbB-2 shedding change under chemotherapy, with less of the c-erbB-2 protein fragment being released to the serum, which would make the c-erbB-2 positive tumor cells a better target for anti-c-erbB-2 antibody treatment.
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Medizinische Klinik, Humboldt-Universität Berlin, Germany. Diana.Lueftner@rz.hu-berlin.de
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D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*
D015295:Antigens, Tumor-Associated, Carbohydrate; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; C090797:CA 27-29 antigen