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Continuous-infusion topotecan and erlotinib: a study in topotecan-pretreated ovarian cancer assessing shed collagen epitopes as a marker of invasiveness.

ABSTRACT: 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.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.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. FIGURE 1: Monitoring of combination treatment. A, B, C, D, and F refer to patients. (A):: Topotecan and erlotinib. (B):: CA-125 in units/mL.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.

SUBMITTER: Warner E

PROVIDER: S-EPMC3958467 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Continuous-infusion topotecan and erlotinib: a study in topotecan-pretreated ovarian cancer assessing shed collagen epitopes as a marker of invasiveness.

Warner Eiran E Liebes Leonard L Levinson Benjamin B Downey Andrea A Tiersten Amy A Muggia Franco F

The oncologist 20140221 3

<h4>Background</h4>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.<h4>Methods</h4>Topotecan 0.4 mg/m(2) per day was administered by continuous infusion for 9-10 days every 3 weeks. Erlotini ...[more]

PMID: 24563078

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Dataset Information

Continuous-infusion topotecan and erlotinib: a study in topotecan-pretreated ovarian cancer assessing shed collagen epitopes as a marker of invasiveness.

Publications

Continuous-infusion topotecan and erlotinib: a study in topotecan-pretreated ovarian cancer assessing shed collagen epitopes as a marker of invasiveness.

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