Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2010 Jun 1;16(11):3028-34.
doi: 10.1158/1078-0432.CCR-09-3122. Epub 2010 May 18.

Clinical and correlative results of SWOG S0354: a phase II trial of CNTO328 (siltuximab), a monoclonal antibody against interleukin-6, in chemotherapy-pretreated patients with castration-resistant prostate cancer

Tanya B Dorff  1 , Bryan Goldman, Jacek K Pinski, Philip C Mack, Primo N Lara Jr, Peter J Van Veldhuizen Jr, David I Quinn, Nicholas J Vogelzang, Ian M Thompson Jr, Maha H A Hussain
Affiliations
Clinical Trial

Clinical and correlative results of SWOG S0354: a phase II trial of CNTO328 (siltuximab), a monoclonal antibody against interleukin-6, in chemotherapy-pretreated patients with castration-resistant prostate cancer

Tanya B Dorff et al. Clin Cancer Res. .

Abstract

Purpose: Interleukin-6 (IL-6) facilitates cancer cell survival via pleotrophic effects. We conducted a multicenter phase II study of CNTO328 (siltuximab) as second-line therapy for men with castration-resistant prostate cancer.

Experimental design: Eligible men had castration-resistant prostate cancer treated with one prior chemotherapy. Subjects were treated with 6 mg/kg CNTO328 i.v. every 2 weeks for 12 cycles. Response was assessed after every three cycles. Primary end point was prostate-specific antigen (PSA) response rate defined as a 50% reduction. Accrual was planned in two stages, with 20 eligible patients in the first stage and 40 overall. Plasma cytokines and growth factors were measured by Luminex.

Results: Fifty-three eligible subjects had all received prior taxane therapy. Two (3.8%; 95% CI, 0.5-13.0%) had PSA response. None of the 31 patients with measurable disease had a RECIST (Response Evaluation Criteria in Solid Tumors) response but 7 (23%) had stable disease. With median follow-up of 14.8 months, median progression-free survival was 1.6 months (95% CI, 1.6-1.7) and median overall survival was 11.6 months (95% CI, 7.5-19.0). Grade 3/4 toxicities included disseminated intravascular coagulation (1), central nervous system ischemia (1), elevated aspartate aminotransferase (1), gastritis/esophagitis (2), thrombocytopenia (2), pain (2), leukopenia (1), and neuropathy (2). Median baseline IL-6 levels were 12.5 pg/mL (interquartile range, 2.5-41.5). Patients with IL-6 >12.5 pg/mL had worse survival than those with levels <12.5 pg/mL (53% versus 94%; P = 0.02). After treatment, IL-6 levels were >250-fold higher. Thirty-two of 38 patients had a decline in C-reactive protein plasma levels at 6 weeks.

Conclusions: CNTO328 resulted in a PSA response rate of 3.8% and a RECIST stable disease rate of 23%. Declining C-reactive protein levels during treatment may reflect biological activity. Despite evidence of CNTO-mediated IL-6 inhibition, elevated baseline IL-6 levels portended a poor prognosis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The Kaplan-Meier curve for progression-free survival in chemotherapy pre-treated patients with castration-resistant prostate cancer treated with monoclonal antibody, CNTO328
Figure 2
Figure 2
The Kaplan-Meier curve for overall survival in chemotherapy pre-treated patients with castration-resistant prostate cancer treated with monoclonal antibody, CNTO328
Figure 3
Figure 3
Survival curves by baseline marker levels in chemotherapy pre-treated patients with castration-resistant prostate cancer treated with monoclonal antibody, CNTO328
See this image and copyright information in PMC

References

    1. A Jemal RS, Ward E, et al. Cancer Statistics. CA Cancer J Clin. 2007;57:43–66. - PubMed
    1. Petrylak DPTC, Hussain MH, Lara PN, Jr, Jones JA, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513–1520. - PubMed
    1. Tannock IF dWR, Berry WR, Horti J, Pluzanska A, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. New Engl J Med. 2004;351(15):1502–1512. - PubMed
    1. Berry DLMC, Jiang CS, Ankerst DP, Petrylak DP, et al. Quality of life and pain in advanced stage prostate cancer: results of a Southwest Oncology Group randomized trial comparing docetaxel and estramustine to mitoxantrone and prednisone. J Clin Oncol. 2006;24(18):2828–2835. - PubMed
    1. Rosenberg JEWV, Kelly WK, Michaelson D, Hussain MH, et al. Activity of second-line chemotherapy in docetaxel-refractory hormone-refractory prostate cancer patients: randomized phase 2 study of ixabepilone or mitoxantrone and prednisone. Cancer. 2007;110(3):556–563. - PubMed

Publication types

Grants and funding