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A phase 1 trial of 2 dose schedules of ABT‐510, an antiangiogenic, thrombospondin‐1‐mimetic peptide, in patients with advanced cancer
Author(s) -
Gordon Michael S.,
Mendelson David,
Carr Robert,
Knight Raymond A.,
Humerickhouse Rod A.,
Ian Maria,
Stopeck Alison T.
Publication year - 2008
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23953
Subject(s) - medicine , nausea , adverse effect , chills , vomiting , dosing , bolus (digestion) , cancer , toxicity , pharmacokinetics , gastroenterology , anesthesia
BACKGROUND. ABT‐510 is a substituted nonapeptide that mimics the antiangiogenic activity of the endogenous protein thrombospondin‐1 (TSP‐1). The current study was designed to establish the safety of ABT‐510 in the treatment of patients with advanced malignancies on a once‐daily (QD) and twice‐daily dosing schedule. METHODS. Patients were randomly assigned to 1 of 6 dosing regimens: 20 mg, 50mg, or 100 mg QD or 10 mg, 25 mg, or 50 mg twice daily. ABT‐510 was administered by subcutaneous bolus injection in cycles of 28 days. Tumor response and disease progression were monitored at 8‐week intervals by computed tomography scan or magnetic resonance imaging. RESULTS. Thirty‐six patients were randomly assigned in equal numbers to the 6 study regimens, with an additional 13 patients randomized to the 10‐mg‐twice‐daily and 50‐mg‐twice‐daily ABT‐510 regimens. The expected pharmacokinetic target was achieved at all dose levels tested. The majority of adverse events were grade 1 or 2 (according to National Cancer Institute Common Toxicity Criteria [version 2]) and were not found to be dose related. The most frequently reported adverse events that were possibly related to ABT‐510 included injection site reactions, asthenia, headache, and nausea. Grade 3 events considered to possibly be related included nausea, dyspnea, bone pain, constipation, vomiting, asthenia, and chills and tremors. One partial response was observed in a patient with carcinosarcoma who received 20 mg QD. The 6‐month progression‐free survival rate was 6%. Approximately 42% of patients (21 of 50 patients) had stable disease for ≥3 months. CONCLUSIONS. ABT‐510 can be administered at doses of 20 mg/day to 100 mg/day without significant toxicity. In the current study, minimal antitumor activity was observed, which was similar to observations in other single‐agent antiangiogenic trials. Cancer 2008. © 2008 American Cancer Society.