Intermittent chemotherapy in patients with metastatic androgen-independent prostate cancer

Results from ASCENT, a double-blinded, randomized comparison of high-dose calcitriol plus docetaxel with placebo plus docetaxel


  • The Oregon Health and Science University (OHSU) and Dr. Beer have a significant financial interest in Novacea, Inc, a company that may have a commercial interest in the results of this research and technology. This potential conflict was reviewed and a management plan approved by the OHSU Conflict of Interest in Research Committee and the Integrity Program Oversight Council was implemented.

    The following were participating investigators who are not included among the authors. Canada (Investigators of the Canadian Urologic Oncology Group): Scott Berry (Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario), Piotr Czaykowski (CancerCare Manitoba, Winnipeg, Manitoba), D. Scott Ernst (London Regional Cancer Centre, London, Ontario), Malcolm Moore (Princess Margaret Hospital-University Health Network, Toronto, Ontario), and Fred Saad (Centre Hospitalier de I'Université de Montréal Hôpital Notre-Dame, Montréal, Qué bec). U.S.: Frederick R. Ahmann (University of Arizona Cancer Center, Tucson, AZ), Ari D. Baron (California Pacific Medical Center, San Francisco, CA), William R. Berry (Raleigh Hematology Oncology Clinic, Cary, NC), Maria B. Bishop (Southern Arizona VA Health Care Sustek, Tucson, AZ), James A. Brown (Associates in Oncology/Hematology, Rockville, MD), Michael A. Carducci (The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD), Tarek A. Chidiac (Mid-Ohio Oncology/Hematology, Inc, Columbus, OH), Luis Chu (Oncology Hematology Consultants, Sarasota, FL), Steven L. Davidson (Montgomery Cancer Center, Montgomery, AL), Robert Dreicer (The Cleveland Clinic Foundation, Cleveland, OH), David M. Ellison (Charleston Hematology Oncology, Charleston, SC), Louis Fehrenbacher (Kaiser Permanente Medical Center, Vallejo, CA), Patrick J. Flynn (Metro-Minnesota CCOP, St. Louis Park, MN), Michael S. Gordon (Arizona Cancer Center, Scottsdale, AZ), Leland M. Green (Tower Cancer Research Foundation, Beverly Hills, CA), Ralph J. Hauke (University of Nebraska Medical Center, Omaha, NE), Celestia S. Higano (Seattle Cancer Care Alliance, Seattle, WA), David H. Irwin (Alta Bates Comprehensive Cancer Center, Berkeley, CA), Vahan S. Kassabian (Georgia Oncology, Atlanta, GA), Manish Kohli (Central Arkansas Veterans Healthcare System, Little Rock, AR), Primo N. Lara, Jr (University of California, Davis Cancer Center, Sacramento, CA), Ellis G. Levine (Roswell Park Cancer Institute, Buffalo, NY), Timothy M. Lopez (New Mexico Cancer Center Associates, Santa Fe, NM), Joseph J. Muscato (Missouri Cancer Associates, Columbia, MO), Ira A. Oliff (Midwest Cancer Research Group, Skokie, IL), Ray D. Page (Texas Cancer Care, Fort Worth, TX), Jonathan A. Polikoff (Southern California Permanente Medical Group, San Diego, CA), Mark U. Rarick (Kaiser Permanente Northwest, Portland, OR), Charles H. Redfern (Sharp Health- Care, San Diego, CA), Donald A. Richards (Tyler Cancer Center, Tyler, TX), Mansoor N. Saleh (Georgia Cancer Specialists, Tucker, GA), Michael A. Savin (Texas Cancer Center at Medical City, Dallas, TX), Mark C. Scholz (Prostate Oncology Specialists, Marina Del Rey, CA), Rakesh Singal (University of Miami Hospital and Clinics, Miami, FL), Daniel Vicario (San Diego Cancer Center, Vista, CA), David M. Waterhouse (Oncology Hematology Care, Cincinnati, OH), and Furhan Yunus (University of Tennessee Cancer Institute, Memphis, TN).



Survival in patients with metastatic, chemotherapy-naive, androgen-independent prostate cancer (AIPC) is improved with 10 to 12 cycles of docetaxel-containing chemotherapy but further management is undefined. In the current study, the authors examined retreatment with the same regimen after a treatment holiday.


Patients treated with docetaxel at a dose of 36 mg/m2 plus either high-dose calcitriol (DN-101; 45 μg) or placebo administered weekly for 3 of every 4 weeks could suspend treatment if their serum prostate-specific antigen (PSA) level was reduced ≥50% and reached a level ≤4 ng/mL. PSA was monitored every 4 weeks (computed tomography scans were administered every 8 weeks in patients with measurable disease) during the treatment holiday. Treatment was resumed when the serum PSA rose by ≥50% and was ≥2 ng/mL or when there was other evidence of disease progression. The study was not powered to compare treatment holiday outcomes between the 2 arms.


A total of 250 patients were randomized 1:1. Overall, 18% of patients (20% in the high-dose calcitriol group and 16% in the placebo group) entered the intermittent chemotherapy arm. The median duration of the first chemotherapy holiday was 18 weeks (range, 4%70 weeks). On resumption of treatment after the first holiday, 45.5% of evaluable patients responded with a ≥50% reduction in serum PSA from their postholiday baseline, 45.5% met the criteria for stable PSA for at least 12 weeks, and 9.1% of patients developed disease progression.


To the authors' knowledge, the current study is the first report of intermittent chemotherapy in patients with AIPC who were prospectively tested in a large multi-institutional trial. This strategy results in a clinically significant duration of chemotherapy holidays and can be offered to a minority of patients. At the time of retreatment, the majority of patients again respond to treatment or their PSA levels stabilized. Additional studies of intermittent chemotherapy are needed to better characterize the optimal patient population and the optimal approach. Cancer 2008. © 2007 American Cancer Society.