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, Bryan Goldman, Jacek K. Pinski, Philip C. Mack, Primo N. Lara, Peter J. Van Veldhuizen, David I. Quinn, Nicholas J. Vogelzang, Ian M. Thompson, Maha H.A. Hussain

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139 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3028-3034
Number of pages7
JournalClinical Cancer Research
Volume16
Issue number11
DOIs
StatePublished - Jun 1 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Dorff, T. B., Goldman, B., Pinski, J. K., Mack, P. C., Lara, P. N., Van Veldhuizen, P. J., Quinn, D. I., Vogelzang, N. J., Thompson, I. M., & Hussain, M. H. A. (2010). 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. Clinical Cancer Research, 16(11), 3028-3034. https://doi.org/10.1158/1078-0432.CCR-09-3122