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01.04.2011 | Original Article

A phase II study of the antisense oligonucleotide GTI-2040 plus docetaxel and prednisone as first-line treatment in castration-resistant prostate cancer

verfasst von: Srikala S. Sridhar, Christina M. Canil, Kim N. Chi, Sebastien J. Hotte, Scott Ernst, Lisa Wang, Eric X. Chen, Agnes Juhasz, Yun Yen, Peter Murray, James A. Zwiebel, Malcolm J. Moore

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2011

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Abstract

Purpose

GTI-2040 is a novel antisense oligonucleotide to the R2 subunit of ribonucleotide reductase. This phase II trial was conducted to determine the efficacy and tolerability of GTI-2040 when combined with docetaxel and prednisone for the treatment of patients with castration-resistant prostate cancer (CRPC).

Methods

Chemo-naïve CRPC patients with adequate performance status and organ function were treated with docetaxel 75 mg/m² IV on day 1 plus GTI-2040 5 mg/kg/day by continuous intravenous infusion day 1–14 on a 21 day cycle, with prednisone 5 mg orally twice daily. The primary endpoint was PSA response rate. Pharmacokinetic studies of GTI-2040 and pharmacodynamic studies on peripheral blood mononuclear cells (PBMC) were also performed.

Results

Twenty-two patients in total (19 from this study and 3 from a prior phase I/II study at this institution) were treated at the recommended phase II dose. A confirmed PSA response was seen in 9/22 patients (41%). Of 16 patients with measurable disease, there was 1 partial response (PR) and 12 stable disease (SD) lasting 3.6 months (median), as best response. The most common toxicities were anemia, fatigue, lymphopenia, leucopenia and neutropenia. Grade 3+ toxicities included neutropenia, lymphopenia, leucopenia, fatigue, febrile neutropenia and hypophosphatemia.

Conclusions

The PSA response rate of GTI-2040 in combination with docetaxel and prednisone just met the minimum phase II criteria for further enrollment. However, after evaluation of all the clinical data, further study of this dose and schedule of GTI-2040 in CRPC was not recommended.

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Titel: A phase II study of the antisense oligonucleotide GTI-2040 plus docetaxel and prednisone as first-line treatment in castration-resistant prostate cancer
verfasst von: Srikala S. Sridhar
Christina M. Canil
Kim N. Chi
Sebastien J. Hotte
Scott Ernst
Lisa Wang
Eric X. Chen
Agnes Juhasz
Yun Yen
Peter Murray
James A. Zwiebel
Malcolm J. Moore
Publikationsdatum: 01.04.2011
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2011
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-010-1389-7

Springer Medizin

A phase II study of the antisense oligonucleotide GTI-2040 plus docetaxel and prednisone as first-line treatment in castration-resistant prostate cancer