Hormone Therapy in Treating Patients With Rising PSA Levels Following Radiation Therapy for Prostate Cancer

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate, recurrent prostate cancer

Brief summary

RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. It is not yet known which androgen suppression regimen is more effective for prostate cancer. PURPOSE: This randomized phase III trial is studying two hormone therapy regimens and comparing them to see how well they work in treating patients with rising PSA levels following radiation therapy for prostate cancer.

Detailed description

OBJECTIVES: * Compare the survival of prostate cancer patients with prostate-specific antigen progression in the clinical absence of distant metastases after prior radical radiotherapy treated with intermittent androgen suppression (IAS) vs continuous androgen deprivation (CAD). * Compare the time to the development of hormone resistance in patients treated with these regimens. * Compare the quality of life of patients treated with these regimens. * Compare the serum cholesterol and HDL/LDL levels at 3 years with those at baseline and compare them annually in patients treated with these regimens. * Evaluate the duration of treatment and non-treatment intervals, time to testosterone recovery (return to pre-therapy levels), and time to recover potency in patients treated with IAS. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior radical prostatectomy (yes vs no), time since completion of prior radical radiotherapy (1 to 3 years vs 3 years or more), baseline prostate-specific antigen (PSA) value (3-15 ng/mL vs greater than 15 ng/mL), and prior hormonal therapy (neo-adjuvant, concurrent, or adjuvant cytoreduction in association with the radical radiotherapy treatment or prostatectomy for a maximum duration of 12 months and completed at least 12 months prior to randomization) (yes vs no). Patients are randomized to one of two treatment arms. * Arm I: Patients undergo intermittent androgen suppression (IAS). Patients receive luteinizing hormone-releasing hormone (LHRH) analog (buserelin \[BSRL\], goserelin \[ZDX\], or leuprolide \[LEUP\]) and an antiandrogen (nilutamide \[ANAN\], flutamide \[FLUT\], bicalutamide \[CDX\], or cyproterone acetate \[CPTR\]) for 8 months. Patients receive LHRH analog by subcutaneous (SC) or intramuscular (IM) implant every 1-4 months beginning within 5 days of randomization and oral antiandrogen 1-3 times daily, depending on the actual LHRH analog and antiandrogen. PSA levels are monitored every 2 months. If PSA falls to normal during the 8-month treatment period, therapy stops until levels rise to 10 ng/mL, at which time IAS resumes for another 8-month period. IAS continues as long as PSA levels are controlled. At the time of disease progression, patients begin continuous hormonal treatment similar to arm II. * Arm II: Patients undergo continuous androgen deprivation without scheduled interruptions. Patients receive LHRH analog (BSRL, ZDX, or LEUP) with an antiandrogen (ANAN, FLUT, CDX, or CPTR) OR undergo bilateral orchiectomy within 5 days of randomization and receive an antiandrogen. Patients receive LHRH analog by SC or IM implant every 1-4 months beginning within 5 days of randomization and oral antiandrogen 1-3 times daily, depending on the actual LHRH analog and antiandrogen. PSA levels are monitored every 2 months. Treatment continues until hormone resistance develops. Patients receiving LHRH analog may begin antiandrogen therapy either prior to or simultaneously with LHRH analog and must continue antiandrogen therapy for at least 4 weeks to block tumor flare. Quality of life is assessed at randomization, every 4 months for 2 years, every 8 months until development of hormone resistance, at the time of hormone resistance, and then annually thereafter. Patients are followed annually for survival. PROJECTED ACCRUAL: A total of 1,386 patients will be accrued for this study within 7 years.

Hamilton RJ, Ding K, Crook JM, O'Callaghan CJ, Higano CS, Dearnaley DP, Horwitz EM, Goldenberg SL, Gospodarowicz MK, Klotz L.

2020-12-3128 citations

10.1016/j.eururo.2020.12.031

MP53-11 COMPARATIVE EFFICACY OF LOCAL VERSUS SYSTEMIC SALVAGE THERAPIES FOR RADIO-RECURRENT PROSTATE CANCER: A SUB-ANALYSIS OF CCTG PR-7

Glenn Bauman, Keyue Ding, Joseph Chin, Shiva M. Nair, Alessandra Iaboni et al. (10 authors)

The Journal of Urology2020-04-01

10.1097/ju.0000000000000915.011

Comparative efficacy of local versus systemic salvage therapies for recurrent prostate cancer after primary radiotherapy.

Glenn Bauman, Keyue Ding, Joseph L. Chin, Alessandra Iaboni, Laurence Klotz et al. (9 authors)

Journal of Clinical Oncology2020-02-19

10.1200/jco.2020.38.6_suppl.221

MP73-04 THE ASSOCIATION BETWEEN STATIN USE AND OUTCOMES IN PATIENTS INITIATING ANDROGEN DEPRIVATION THERAPY

Robert G. Hamilton, Keyue Ding, Juanita Crook, Christopher O’Callaghan, Celestia S. Higano et al. (10 authors)

The Journal of Urology2015-03-312 citations

10.1016/j.juro.2015.02.2680

The association between statin use and outcomes in patients initiating androgen deprivation therapy.

Robert J. Hamilton, Keyue Ding, Juanita Crook, Christopher J. O’Callaghan, Celestia S. Higano et al. (10 authors)

Journal of Clinical Oncology2015-03-015 citations

10.1200/jco.2015.33.7_suppl.145

Intermittent androgen suppression for rising PSA level after radiotherapy.

Crook JM, O'Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, Frymire E, Malone S, Chin J, Nabid A, Warde P, Corbett T, Angyalfi S, Goldenberg SL, Gospodarowicz MK, Saad F, Logue JP, Hall E, Schellhammer PF, Ding K, Klotz L.

2012-09-01349 citations

10.1056/nejmoa1201546

Interventions

DRUGbicalutamide

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

DRUGbuserelin

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

DRUGcyproterone acetate

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

DRUGflutamide

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

DRUGgoserelin

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

DRUGleuprolide acetate

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

DRUGnilutamide

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

16 Years to 120 Years

Healthy volunteers

No

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically or cytologically proven adenocarcinoma of the prostate prior to the initiation of radiotherapy * Prior pelvic radiotherapy for prostate cancer, either post-radical prostatectomy or as primary management * More than 30 months since prior brachytherapy with curative intent * Prostate-specific antigen must be rising and greater than 3 ng/mL and higher than the lowest level recorded previously since the end of radiotherapy (i.e., higher than the post-radiotherapy nadir) * Total testosterone greater than 5 nmol/L * No definite evidence of metastatic disease * Chest x-ray and bone scan negative for metastases * Radiological changes compatible with nonmalignant diseases allowed * Clinical evidence of local disease allowed PATIENT CHARACTERISTICS: Age: * 16 and over (18 and over for participating centers in the United Kingdom) Performance status: * ECOG 0-1 Life expectancy: * More than 5 years Hematopoietic: * Not specified Hepatic: * Bilirubin no greater than 1.5 times upper limit of normal (ULN) * AST/ALT no greater than 1.5 times ULN * LDH no greater than 1.5 times ULN * No chronic liver disease Renal: * Creatinine no greater than 1.5 times ULN Other: * Sufficiently fluent and willing to complete the quality of life questionnaire in either English or French * Fertile patients must use effective contraception * No other malignancy within the past 5 years except curatively treated basal or squamous cell skin cancer or superficial bladder cancer PRIOR CONCURRENT THERAPY: Biologic therapy: * No prior or concurrent biologic therapy Chemotherapy: * No prior or concurrent chemotherapy Endocrine therapy: * Prior hormonal therapy administered prior to, during, or immediately after radical radiotherapy or prostatectomy allowed provided duration was no longer than 12 months * At least 12 months since prior hormonal therapy Radiotherapy: * See Disease Characteristics * At least 12 months since prior radiotherapy * No concurrent palliative radiotherapy Surgery: * See Disease Characteristics * See Endocrine therapy Other: * No concurrent bisphosphonates

Design outcomes

Primary

Measure	Time frame
Overall survival	2 years

Secondary

Measure	Time frame
Quality of life by European Organization for Research of the Treatment of Cancer Quality of Life Questionnaire-C30+ (EORTC QLQ-C30+) trial specific checklist	2 years
Serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels	2 years
Time to hormone resistance	2 years
Time to testosterone recovery during intermittent androgen suppression arm only	2 years
Time to recovery of potency during intermittent androgen suppression arm only	2 years
Duration of treatment and non-treatment interval during intermittent androgen suppression arm only	2 years

Countries

Canada

Outcome results

None listed