Back to Search
Start Over
An open-label, multicenter, phase I/II study of single-agent AT-101 in men with castrate-resistant prostate cancer.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2009 May 01; Vol. 15 (9), pp. 3172-6. Date of Electronic Publication: 2009 Apr 14. - Publication Year :
- 2009
-
Abstract
- Purpose: AT-101 binds and inhibits the antiapoptotic function of Bcl-2, Bcl-xL, Mcl-1, and Bcl-w and is a potent stimulator of proapoptotic proteins. In this multi-institution phase I/II trial, we evaluated the safety and efficacy of single-agent AT-101, in men with chemotherapy naïve, castrate-resistant prostate cancer (CRPC).<br />Experimental Design: Patients with progressive CRPC were to be treated with escalating doses of AT-101 on a continuous daily basis until the maximally tolerated dose was achieved. At the recommended phase 2 dose, an additional 21 patients were planned to assess for preliminary evidence of efficacy.<br />Results: Twenty-three patients were enrolled. The phase I starting dose was 30 mg/day on a continuous basis; however, ongoing trials with AT-101 showed increased gastrointestinal toxicity with this daily schedule when given for repetitive cycles. As a result, the phase II starting dose was chosen to be 30 mg/day for 21 of 28 days. The most frequent observed adverse events (any grade) were diarrhea (43.5%), fatigue (34.8%), nausea (21.7%), anorexia (21.7%), and small intestinal obstruction (21.7%). Due to the high incidence of grade 3 small intestinal obstruction (n = 5; 21.7%), a reduction in dose to 20 mg/day for 21 of 28 days was mandated for all patients. Two patients had a confirmed > or =50% posttherapy prostate-specific antigen decline. No objective responses (Response Evaluation Criteria in Solid Tumors) were observed.<br />Conclusion: AT-101 administered at 20 mg/day for 21 of 28 days was well-tolerated. Evidence of single-agent clinical activity was observed with prostate-specific antigen declines in some patients. Further investigation of AT-101 in prostate cancer is warranted and trials combining AT-101 with androgen deprivation, as well as with docetaxel chemotherapy are ongoing.
- Subjects :
- Adenocarcinoma blood
Adenocarcinoma secondary
Administration, Oral
Aged
Aged, 80 and over
Cohort Studies
Drug Administration Schedule
Gossypol therapeutic use
Humans
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Staging
Neoplasms, Hormone-Dependent blood
Neoplasms, Hormone-Dependent pathology
Prognosis
Prostate-Specific Antigen blood
Prostatic Neoplasms blood
Prostatic Neoplasms pathology
Treatment Outcome
Adenocarcinoma drug therapy
Antineoplastic Agents, Phytogenic therapeutic use
Gossypol analogs & derivatives
Neoplasms, Hormone-Dependent drug therapy
Orchiectomy
Prostatic Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0432
- Volume :
- 15
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 19366825
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-08-2985