NCT00002597 · CITED IN SOURCE DOCUMENTS

Radiation Therapy With or Without Antiandrogen Therapy in Treating Patients With Stage I or Stage II Prostate Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2018-06-14

RATIONALE: Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using flutamide, goserelin, and leuprolide may fight prostate cancer by reducing the production of androgens. It is not yet known which regimen of antiandrogen therapy is most effective for prostate cancer. PURPOSE: Randomized phase III trial to study the effectiveness of radiation therapy with or without antiandrogen therapy in treating patients who have stage I or stage II prostate cancer.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival Rate (10-year)

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outcome · POSTED

Disease-specific Survival Rate (10 Years)

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outcome · POSTED

Local Progression Rate (10 Years)

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outcome · POSTED

Distant Failure Rate (10 Years)

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outcome · POSTED

Biochemical Failure Rate (10 Years)

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outcome · POSTED

Clinical Relapse Rate (10 Years)

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outcome · POSTED

Second Biochemical Relapse Rate (10 Years)

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outcome · POSTED

Disease-free Survival Rate (10 Years)

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outcome · POSTED

Positive Re-biopsy Rate at Two Years

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion criteria: * Histologically confirmed locally confined adenocarcinoma of the prostate with primary tumors confined to the prostate, clinical stage T1b,1c, 2a or 2b. * Negative nodes evaluated by imaging methods (classified in the study as NX) or by surgical sampling (classified in the study as N0). * Karnofsky performance status ≥ 70. * PSA is mandatory, must be ≤ 20) * No prior hormonal therapy, radiation or chemotherapy. * Prior finasteride for prostate hypertrophy allowed if discontinued at least 60 days prior to randomization. * Prior testosterone administration allowed if at least 90 days elapsed since last administration. * No evidence of distant metastasis or other synchronous primary. Patients with prior invasive malignancy who were disease free for at least 5 years could be eligible with pre-randomization approval by the study chairman. * Treatment begins within 21 days after randomization. * Patients signs a study-specific informed consent form. * Alanine Aminotransferase (ALT) within 2x upper normal limits. Exclusion criteria: * Stage T1a or ≥ T2c disease. * Lymph node involvement (N1 - N3). * Evidence of distant metastasis. (M1) * PSA \> 20. * Radical surgery or cryosurgery for carcinoma of the prostate, previous irradiation, antiandrogen therapy or chemotherapy. * Previous or concurrent cancers other than basal cell or squamous cell skin carcinoma. Patients with squamous cell carcinomas required to be NED (no evidence of disease) for a minimum of two years prior to study entry. * Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow-up. * Karnofsky performance status of \< 70.
healthy Volunteers: false
minimum Age: 18 Years
sex: MALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
intervention Names
Drug: flutamide
Drug: Zoladex
Drug: Lupron
Radiation: radiation therapy
label
Neoadjuvant TAS + RT
type
EXPERIMENTAL
description
Radiation therapy alone
intervention Names
Radiation: radiation therapy
label
Radiation therapy alone
type
OTHER

interventions

arm Group Labels
Neoadjuvant TAS + RT
description
Two 125 mg capsules (t.i.d., p.o.) beginning two months before RT and continuing until RT is completed.
name
flutamide
other Names
Eulexin
type
DRUG
arm Group Labels
Neoadjuvant TAS + RT
description
3.6 mg s.c. monthly x 4 beginning two months before RT and continuing until RT is completed. The 3-month preparation may be used instead of three separate monthly injections.
name
Zoladex
other Names
goserelin acetate
type
DRUG
arm Group Labels
Neoadjuvant TAS + RT
description
7.5 mg IM (intramuscular) monthly x 4 beginning two months before RT and continuing until RT is completed. The 3-month preparation may be used instead of three separate monthly injections.
name
Lupron
other Names
leuprolide acetate
type
DRUG
arm Group Labels
Neoadjuvant TAS + RT
Radiation therapy alone
description
46.8 Gy (1.8 Gy/day four to five times a week \[26 fx\]) to regional lymphatics followed by 19.8 Gy (1.8 Gy/day x 11 fx) for a total of 66.6 Gy to the prostate. Prostate only may be treated in defined circumstances.
name
radiation therapy
type
RADIATION

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 2028
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Overall survival (OS) was calculated from randomization to the date of death from any cause and overall survival rates were estimated by the Kaplan-Meier method.
measure
Overall Survival Rate (10-year)
time Frame
From date of randomization to 10 years

secondary Outcomes

description
Disease-specific failure is defined as death certified as due to prostate cancer (by central review), death due to complications of treatment (irrespective of malignancy status), death from unknown causes with active malignancy, or death from unknown causes with previously documented relapse (either clinical or biochemical). Survival rates were estimated by means of cumulative incidence functions.
measure
Disease-specific Survival Rate (10 Years)
time Frame
From registration to 10 years
description
Local progression defined as documented local progression as determined by clinical exam . Failure rates were estimated by means of cumulative incidence functions.
measure
Local Progression Rate (10 Years)
time Frame
From registration to 10 years
description
Failure is defined as documented metastatic disease. Failure rates were estimated by means of cumulative incidence functions.
measure
Distant Failure Rate (10 Years)
time Frame
From registration to 10 years
description
The Phoenix definition of biochemical failure was used - an increase in the prostate-specific antigen (PSA) level of \>2 ng per milliliter above the nadir. Failure rates were estimated by means of cumulative incidence functions.
measure
Biochemical Failure Rate (10 Years)
time Frame
From registration to 10 years
description
Clinical relapse is defined as local progression or distant metastases. Failure rates were estimated by means of cumulative incidence functions.
measure
Clinical Relapse Rate (10 Years)
time Frame
From registration to 10 years
description
Second biochemical relapse is as defined as follows (after initiation of salvage hormone therapy): A rise in PSA on at least two consecutive cases above the nadir (after initiation of salvage hormone therapy), with the rises in PSA exceeding 1 ng/ml above the nadir; or failure to reach 4 ng/L or less at 18 months. The rates of second biochemical relapse were estimated by means of cumulative incidence functions.
measure
Second Biochemical Relapse Rate (10 Years)
time Frame
From registration to 10 years
description
Disease-free failure is defined as documentation of progression (local progression, distant failure, and biochemical failure) or death from any cause. Disease-free survival rates were estimated by the Kaplan-Meier method.
measure
Disease-free Survival Rate (10 Years)
time Frame
From registration to 10 years
description
The rate of prostate rebiopsy at two years is defined as the proportion of patients whose results are positive among all eligible patients who had a repeat biopsy at two years. The rate was estimated separately in each arm.
measure
Positive Re-biopsy Rate at Two Years
time Frame
From registration to two years

Full study description

brief Summary: RATIONALE: Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using flutamide, goserelin, and leuprolide may fight prostate cancer by reducing the production of androgens. It is not yet known which regimen of antiandrogen therapy is most effective for prostate cancer. PURPOSE: Randomized phase III trial to study the effectiveness of radiation therapy with or without antiandrogen therapy in treating patients who have stage I or stage II prostate cancer.
detailed Description: OBJECTIVES: Primary: To evaluate whether a combination of Zoladex and flutamide used as cytoreductive agents prior to and during definitive radiation therapy improves overall survival over radiation therapy alone in locally confined carcinomas of the prostate; Secondary: To compare the rates of disease-specific survival, clinical relapse (local progression and/or distant failure), freedom from prostate-specific antigen (PSA) failure, freedom from second clinical relapse, freedom from second PSA relapse, and disease-free survival; To compare the prostate re-biopsy at two years; To measure the effect on sexual function. OUTLINE: This is a randomized, multicenter study. Patients were stratified by PSA level (less than 4 vs 4-20), tumor differentiation (well vs moderate vs poor), nodal status (N0 \[nodes evaluated by surgical sampling\] vs NX \[nodes evaluated negative by imaging methods only\]), and participating center. Patients are randomized to one of two treatment arms. Arm I: Patients receive oral flutamide 3 times a day and goserelin subcutaneously once every 4 weeks, or once as a time release injection (intramuscular leuprolide may be substituted for goserelin), beginning 2 months prior to radiotherapy and continuing until completion of radiotherapy. Patients undergo radiotherapy daily 4-5 days per week for almost 8 weeks. Arm II: Patients undergo radiotherapy only, as in arm I. Patients are followed every 3 months for the remainder of the first year, every 4 months for the second year, every 6 months for the third through fifth years, and then annually thereafter. PROJECTED ACCRUAL: A total of 1980 patients within 5 years.

Source references

references

citation
Bruner D, Scott C, McGowan D, et al.: Factors influencing sexual outcomes in prostate cancer patients enrolled on radiation therapy oncology group studies 90-20 and 94-08. [Abstract] Proceedings of the International Society for Quality of Life Research 7: 575, 1998.
type
BACKGROUND
citation
Bruner DW, Scott CB, McGowan D, et al.: Validation of the sexual adjustment questionnaire (SAQ) in prostate cancer patients enrolled on Radiation Therapy Oncology Group studies 90-20 and 94-08. [Abstract] Int J Radiat Oncol Biol Phys 42 (suppl 1): A-156, 202, 1998.
type
BACKGROUND
citation
Johnke RM, Edwards JM, Evans MJ, Nangami GN, Bakken NT, Kilburn JM, Lee TK, Allison RR, Karlsson UL, Arastu HH. Circulating cytokine levels in prostate cancer patients undergoing radiation therapy: influence of neoadjuvant total androgen suppression. In Vivo. 2009 Sep-Oct;23(5):827-33.
pmid
19779119
type
BACKGROUND
citation
Jones CU, Hunt D, McGowan DG, Amin MB, Chetner MP, Bruner DW, Leibenhaut MH, Husain SM, Rotman M, Souhami L, Sandler HM, Shipley WU. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011 Jul 14;365(2):107-18. doi: 10.1056/NEJMoa1012348.
pmid
21751904
type
RESULT
citation
McGowan D, Hunt D, Jones C, et al.: Effect of short-term endocrine therapy prior to and during radiation therapy on overall survival in patients with T1b-T2b adenocarcinoma of the prostate and PSA equal to or less than 20: initial results of RTOG 94-08. [Abstract] 2010 Genitourinary Cancers Symposium, March 5-7, 2010, San Francisco, California. A-6, 2010.
type
RESULT
citation
Spratt DE, Tang S, Sun Y, Huang HC, Chen E, Mohamad O, Armstrong AJ, Tward JD, Nguyen PL, Lang JM, Zhang J, Mitani A, Simko JP, DeVries S, van der Wal D, Pinckaers H, Monson JM, Campbell HA, Wallace J, Ferguson MJ, Bahary JP, Schaeffer EM, Sandler HM, Tran PT, Rodgers JP, Esteva A, Yamashita R, Feng FY. Artificial Intelligence Predictive Model for Hormone Therapy Use in Prostate Cancer. NEJM Evid. 2023 Aug;2(8):EVIDoa2300023. doi: 10.1056/EVIDoa2300023. Epub 2023 Jun 29.
pmid
38320143
type
DERIVED
citation
Jones CU, Pugh SL, Sandler HM, Chetner MP, Amin MB, Bruner DW, Zietman AL, Den RB, Leibenhaut MH, Longo JM, Bahary JP, Rosenthal SA, Souhami L, Michalski JM, Hartford AC, Amin PP, Roach M 3rd, Yee D, Efstathiou JA, Rodgers JP, Feng FY, Shipley WU. Adding Short-Term Androgen Deprivation Therapy to Radiation Therapy in Men With Localized Prostate Cancer: Long-Term Update of the NRG/RTOG 9408 Randomized Clinical Trial. Int J Radiat Oncol Biol Phys. 2022 Feb 1;112(2):294-303. doi: 10.1016/j.ijrobp.2021.08.031. Epub 2021 Sep 1.
pmid
34481017
type
DERIVED

Source notices and limitations

Discovery and provenance

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ion therapy has shown benefit in at least some patients with clinically localized prostate cancer. In an open-label, randomized trial (<a href="/clinicaltrials/NCT00002597">RTOG-9408 </a> [NCT00002597]), 1,979 men with nonmetastatic stage T1b–c, T2a, or T2b tumors and a PSA level of 20 ng/mL or less were randomly assigned
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n at least some patients with clinically localized prostate cancer. In an open-label, randomized trial (<a href="/clinicaltrials/NCT00002597">RTOG-9408 </a> [NCT00002597]), 1,979 men with nonmetastatic stage T1b–c, T2a, or T2b tumors and a PSA level of 20 ng/mL or less were randomly assigned to receive radiation therapy (
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Prostate Cancer Treatment (PDQ®)–Health Professional Version
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Updated: May 14, 2025
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Preserved source evidence · Not medical advice