Continuous-Infusion Topotecan and Erlotinib: A Study in Topotecan-Pretreated Ovarian Cancer Assessing Shed Collagen Epitopes as a Marker of Invasiveness. (21st February 2014)

• Record Type: Journal Article
• Authors: Warner, Eiran; Liebes, Leonard; Levinson, Benjamin; Downey, Andrea; Tiersten, Amy; Muggia, Franco
• Is Part Of: Oncologist. Volume 19:Number 3(2014)
• Page Start: 250
• Page End: 250
• Publication Date: 2014-02-21
• Subjects: Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2013-0398
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract : Background: Continuous-infusion topotecan with erlotinib has the potential to reverse topotecan resistance due to drug efflux mechanisms. We assessed the activity of such a regimen in ovarian cancer patients previously failing bolus topotecan. Assay for shed collagen epitopes recognized by antibody HU177 during treatment explored its ability to reflect tumor invasion. Methods: Topotecan 0.4 mg/m 2 per day was administered by continuous infusion for 9–10 days every 3 weeks. Erlotinib, 150 mg orally, was administered on days 1–10 of each cycle. Cycles were repeated until progression or toxicity. Serum for shed HU177 collagen epitopes was collected weekly. This was a two-stage design to detect a CA-125 response rate of at least 20% in 30 patients after completing two treatment cycles. The trial would be terminated early if there were less than two CA-125 responses in 16 patients. Four or more CA-125 responses in 30 patients would justify further study of this regimen in prior topotecan treatment failures. Results: Six patients were enrolled, with four receiving three or more cycles and one achieving a partial response by cancer antigen 125 (CA-125) criteria. Shed epitope levels became undetectable on at least one measurement in all patients who received three or more cycles (Fig. 1A ) and reappeared concomitantly with rises in CA-125 and clinical progression (Fig. 1B ). After logistical delays, the trial was closed by the sponsor's decision to stop developing erlotinib in ovarian cancer. Conclusion: Continuous-infusion topotecan with erlotinib was found safe in six pretreated ovarian cancer patients; one met CA-125 criteria for partial response. Serial shed epitope levels to reflect invasiveness deserve further study.