Clinical Trials of Adjuvant Androgen Deprivation in Localized Prostate Cancer (AADLPC)

• ClinicalTrials.gov Identifier: NCT02175212
• Recruitment Status: Completed
• First Posted: June 26, 2014
• Results First Posted: November 4, 2016
• Last Update Posted: November 20, 2020
• Sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• Information provided by (Responsible Party): Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Adenocarcinoma
• Interventions: Drug: Short term androgen deprivation; Drug: Long term androgen deprivation; Radiation: Short term androgen deprivation; Radiation: Long term androgen deprivation
• Enrollment: 362

Participant Flow

Recruitment Details	Between Nov 7, 2005, and Dec 20, 2010, 362 were registered. Of these, seven did not meet the inclusion criteria. The final trial population thus consisted of 355 men, of whom 178 were randomly assigned to the short-term androgen deprivation group and 177 to the long-term androgen deprivation group.
Pre-assignment Details

Arm/Group Title	Long Term Androgen Deprivation	Short Term Androgen Deprivation
Arm/Group Description	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy Short term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months) - Bicalutamide 50 mg tablet every day for 2 months Short term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)
Period Title: Overall Study
Started	177	178
Completed	14	31
Not Completed	163	147

Baseline Characteristics

Arm/Group Title		Long Term Androgen Deprivation	Short Term Androgen Deprivation	Total
Arm/Group Description		Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy Short term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months) - Bicalutamide 50 mg tablet every day for 2 months Short term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)	Total of all reporting groups
Overall Number of Baseline Participants		177	178	355
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	177 participants	178 participants	355 participants
		71; (56 to 82)	72; (54 to 85)	71; (54 to 85)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	177 participants	178 participants	355 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	177 100.0%	178 100.0%	355 100.0%
Risk subgroup (intermediate vs. high); Measure Type: Number; Unit of measure: Participants	Number Analyzed	177 participants	178 participants	355 participants
Intermediate		85	81	166
High		92	97	189
T stage (categorical) [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	177 participants	178 participants	355 participants
T1: tumor neither palpable not visible by imaging		38	42	80
T2: Tumor confinent whitin prostate		100	103	203
T3: Tumor extends through the prostate capsule		39	33	72
		[1] Measure Description: Patients were staged according to the AJCC Cancer Staging criteria, 6th edition. Intermediate-risk and high-risk factors were defined following the 2005 guidelines of the National Comprehensive Cancer Network.
PSA (continous); Median (Full Range); Unit of measure: Nanogrames per milliliter (ng/mL)
	Number Analyzed	177 participants	178 participants	355 participants
		11.1; (3.1 to 72.0)	11.0; (3.4 to 66.0)	11; (3.1 to 72.0)
PSA (categorical); Measure Type: Number; Unit of measure: Participants	Number Analyzed	177 participants	178 participants	355 participants
<10 ng/mL		80	74	154
10-20 ng/mL		61	64	125
>20 ng/mL		36	40	76
Gleason score (categorical) [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	177 participants	178 participants	355 participants
<=6		21	30	51
7		110	103	213
8-10		46	45	91
		[1] Measure Description: Gleason classification for prostate cancer were used considering Gleason 6 as less aggressive and Gleason 10 most aggressive
Positive biopsy samples (continous); Median (Full Range); Unit of measure: Number of cylindres
	Number Analyzed	177 participants	178 participants	355 participants
		4; (1 to 13)	4; (1 to 16)	4; (1 to 16)
Prostate radiotherapy dose (continous); Median (Full Range); Unit of measure: Grays (Gy)
	Number Analyzed	177 participants	178 participants	355 participants
		78.0; (30.6 to 88.4)	78.0; (64.0 to 82.2)	78.0; (30.6 to 88.4)
Prostate radiotherapy dose (categorical) [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	177 participants	178 participants	355 participants
<78 Gy		43	51	94
>= 78 Gy		128	122	250
		[1] Measure Description: 173 evaluable patients in short term group and 171 in the long term group
Pelvic radiotherapy (categorical) [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	177 participants	178 participants	355 participants
Yes		20	28	48
No		148	145	293
Missing		3	0	3
		[1] Measure Description: 173 evaluable patients in short term group and 171 in the long term group

Outcome Measures

1. Primary Outcome

Title	Biochemical Disease Free Survival: Estimated Percentage of Participants With Biochemical Disease-free Survival at 5 Years
Description	Biochemical relapse was defined as the time from inclusion in the study (randomization) until the patient meets criteria for Biochemical failure (Phoenix criteria: PSA nadir plus 2 ng/ml).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Long Term Androgen Deprivation	Short Term Androgen Deprivation
Arm/Group Description:	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy Short term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months) - Bicalutamide 50 mg tablet every day for 2 months Short term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)
Overall Number of Participants Analyzed	177	178
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	90; (87 to 92)	81; (78 to 81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Long Term Androgen Deprivation, Short Term Androgen Deprivation
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.01
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.88
	Confidence Interval	(2-Sided) 95%; 1.12 to 3.15
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Metastasis Free Survival: Estimated Percentage of Participants With Metastasis-free Survival at 5 Years
Description	Metastasis free survival: defined as the time from inclusion in the study (randomization) until the appearance of distant metastases: a positive result in any of the tests performed (scintigraphy, chest radiography, thorax, abdominal and pelvic CT and MRI).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Long Term Androgen Deprivation	Short Term Androgen Deprivation
Arm/Group Description:	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy Short term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months) - Bicalutamide 50 mg tablet every day for 2 months Short term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)
Overall Number of Participants Analyzed	177	178
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	94; (92 to 96)	83; (80 to 86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Long Term Androgen Deprivation, Short Term Androgen Deprivation
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.01
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.31
	Confidence Interval	(2-Sided) 95%; 1.23 to 3.85
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Survival: Estimated Percentage of Participants Alive at 5 Years
Description	Overall Survival: defined as the time that elapses from the patient enters the study until the patient dies from any cause.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Long Term Androgen Deprivation	Short Term Androgen Deprivation
Arm/Group Description:	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy Short term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months) - Bicalutamide 50 mg tablet every day for 2 months Short term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)
Overall Number of Participants Analyzed	177	178
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	95; (93 to 97)	86; (83 to 89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Long Term Androgen Deprivation, Short Term Androgen Deprivation
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.009
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.48
	Confidence Interval	(2-Sided) 95%; 1.31 to 4.68
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Cause-specific Survival
Description	Cause-specific survival included all deaths from prostate cancer or treatment complications, and deaths from unknown causes in patients with either active cancer or a previously documented relapse
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Long Term Androgen Deprivation	Short Term Androgen Deprivation
Arm/Group Description:	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy Short term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months) - Bicalutamide 50 mg tablet every day for 2 months Short term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)
Overall Number of Participants Analyzed	177	178
Measure Type: Number; Unit of Measure: participants
	177	173

5. Secondary Outcome

Title	Late Toxicity
Description	Defined as the maximal rectal, urinary and cardiovascular (CV) toxicity per patient more than 90 days after completion of RT. Scoring scales used were the radiation morbidity scoring criteria of the European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group (EORTC/RTOG) and the Common Terminology Criteria for Adverse Events (CTCAEs) v 3.0 for the remained toxicity. CV events were defined according to the World Health Organization criteria
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Long Term Androgen Deprivation	Short Term Androgen Deprivation
Arm/Group Description:	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy Short term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months) - Bicalutamide 50 mg tablet every day for 2 months Short term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)
Overall Number of Participants Analyzed	177	178
Measure Type: Number; Unit of Measure: percentage of patients
Grade 2 of more rectal toxicity	11.1	7.6
Grade 2 of more urinary toxicity	8.2	7.3
Cardiovascular	17.6	7.2

Adverse Events

Time Frame	63 months (IQR 50-82)
Adverse Event Reporting Description	Maximum toxicity per patient
Arm/Group Title	Long Term Androgen Deprivation		Short Term Androgen Deprivation
Arm/Group Description	Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy Long term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)		Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months); Bicalutamide 50 mg tablet every day for 2 months; High dose conformal radiotherapy Short term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months) - Bicalutamide 50 mg tablet every day for 2 months Short term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy)
All-Cause Mortality
	Long Term Androgen Deprivation		Short Term Androgen Deprivation
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Long Term Androgen Deprivation		Short Term Androgen Deprivation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/177 (20.34%)		29/178 (16.29%)
Cardiac disorders
Miocardial Infarction/Ischemic disease † 1	11/177 (6.21%)	11	4/178 (2.25%)	4
Infections and infestations
Sepsis † 1	2/177 (1.13%)	2	4/178 (2.25%)	4
Musculoskeletal and connective tissue disorders
Osteoporotic fracture † 1	2/177 (1.13%)	2	0/178 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Second malignancies † 1	12/177 (6.78%)	12	14/178 (7.87%)	15
Vascular disorders
Tromboembolic disease † 1	4/177 (2.26%)	4	4/178 (2.25%)	4
Cerebrovascular accident (CVA) † 1	5/177 (2.82%)	5	3/178 (1.69%)	3
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (Unspecified)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Long Term Androgen Deprivation		Short Term Androgen Deprivation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	62/177 (35.03%)		40/178 (22.47%)
Gastrointestinal disorders
Rectal bleeding † 1 [1]	12/177 (6.78%)	12	14/178 (7.87%)	14
General disorders
Asthenia † 1	13/177 (7.34%)	13	3/178 (1.69%)	3
Metabolism and nutrition disorders
Hot flashes † 1 [1]	28/177 (15.82%)	28	13/178 (7.30%)	13
Renal and urinary disorders
Urinary toxicity † 1 [1]	9/177 (5.08%)	9	10/178 (5.62%)	10
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (Unspecified); [1] Grade 2 or more according EORTC/RTOG and CTCAE v 3.0

Limitations and Caveats

• Relatively short follow-up and low number of events.
• The lack of patient-reported outcomes.
• Our decision to include vascular events other than strictly cardiac events (e.g. the presence of CVA or thromboembolic disease).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Almudena Zapatero
• Organization: Hospital Universitario de la Princesa; Health Research Institute IIS from Hospital Universitario de la Princesa
• Phone: +34 91 520 23 15
• EMail: almudena.zapatero@salud.madrid.org

Publications of Results:

Zapatero A, Valcarcel F, Calvo FA, Algas R, Bejar A, Maldonado J, Villa S. Risk-adapted androgen deprivation and escalated three-dimensional conformal radiotherapy for prostate cancer: Does radiation dose influence outcome of patients treated with adjuvant androgen deprivation? A GICOR study. J Clin Oncol. 2005 Sep 20;23(27):6561-8. doi: 10.1200/JCO.2005.09.662.

Other Publications:

Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, von Eschenbach AC, Kuban DA, Rosen I. Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002 Aug 1;53(5):1097-105. doi: 10.1016/s0360-3016(02)02829-8.

Zelefsky MJ, Leibel SA, Gaudin PB, Kutcher GJ, Fleshner NE, Venkatramen ES, Reuter VE, Fair WR, Ling CC, Fuks Z. Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys. 1998 Jun 1;41(3):491-500. doi: 10.1016/s0360-3016(98)00091-1.

Zelefsky MJ, Fuks Z, Hunt M, Lee HJ, Lombardi D, Ling CC, Reuter VE, Venkatraman ES, Leibel SA. High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer. J Urol. 2001 Sep;166(3):876-81. Erratum In: J Urol 2001 Nov;166(5):1839.

Vicini FA, Abner A, Baglan KL, Kestin LL, Martinez AA. Defining a dose-response relationship with radiotherapy for prostate cancer: is more really better? Int J Radiat Oncol Biol Phys. 2001 Dec 1;51(5):1200-8. doi: 10.1016/s0360-3016(01)01799-0.

Hanks GE, Hanlon AL, Epstein B, Horwitz EM. Dose response in prostate cancer with 8-12 years' follow-up. Int J Radiat Oncol Biol Phys. 2002 Oct 1;54(2):427-35. doi: 10.1016/s0360-3016(02)02954-1.

Leibel SA, Fuks Z, Zelefsky MJ, Hunt M, Burman CM, Mageras GS, Chui CS, Jackson A, Amols HI, Ling CC. Technological advances in external-beam radiation therapy for the treatment of localized prostate cancer. Semin Oncol. 2003 Oct;30(5):596-615. doi: 10.1016/s0093-7754(03)00354-3.

Joon DL, Hasegawa M, Sikes C, Khoo VS, Terry NH, Zagars GK, Meistrich ML, Pollack A. Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation. Int J Radiat Oncol Biol Phys. 1997 Jul 15;38(5):1071-7. doi: 10.1016/s0360-3016(97)00303-9.

Zietman AL, Prince EA, Nakfoor BM, Shipley WU. Neoadjuvant androgen suppression with radiation in the management of locally advanced adenocarcinoma of the prostate: experimental and clinical results. Urology. 1997 Mar;49(3A Suppl):74-83. doi: 10.1016/s0090-4295(97)00173-8.

Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Lino Cutajar C, Zurlo A, Pierart M. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002 Jul 13;360(9327):103-6. doi: 10.1016/s0140-6736(02)09408-4.

Pilepich MV, Winter K, John MJ, Mesic JB, Sause W, Rubin P, Lawton C, Machtay M, Grignon D. Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2001 Aug 1;50(5):1243-52. doi: 10.1016/s0360-3016(01)01579-6.

Lawton CA, Winter K, Murray K, Machtay M, Mesic JB, Hanks GE, Coughlin CT, Pilepich MV. Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85-31 evaluating the potential benefit of androgen suppression following standard radiation therapy for unfavorable prognosis carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2001 Mar 15;49(4):937-46. doi: 10.1016/s0360-3016(00)01516-9.

Granfors T, Modig H, Damber JE, Tomic R. Combined orchiectomy and external radiotherapy versus radiotherapy alone for nonmetastatic prostate cancer with or without pelvic lymph node involvement: a prospective randomized study. J Urol. 1998 Jun;159(6):2030-4. doi: 10.1016/S0022-5347(01)63235-X.

Zagars GK, Johnson DE, von Eschenbach AC, Hussey DH. Adjuvant estrogen following radiation therapy for stage C adenocarcinoma of the prostate: long-term results of a prospective randomized study. Int J Radiat Oncol Biol Phys. 1988 Jun;14(6):1085-91. doi: 10.1016/0360-3016(88)90383-5.

Pilepich MV, Winter K, Lawton CA, Krisch RE, Wolkov HB, Movsas B, Hug EB, Asbell SO, Grignon D. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1285-90. doi: 10.1016/j.ijrobp.2004.08.047.

Jani AB, Basu A, Abdalla I, Connell PP, Krauz L, Vijayakumar S. Impact of hormone therapy when combined with external beam radiotherapy for early-stage, intermediate-, or high-risk prostate cancer. Am J Clin Oncol. 2003 Aug;26(4):382-5. doi: 10.1097/01.COC.0000026483.80660.94.

Nguyen KH, Horwitz EM, Hanlon AL, Uzzo RG, Pollack A. Does short-term androgen deprivation substitute for radiation dose in the treatment of high-risk prostate cancer? Int J Radiat Oncol Biol Phys. 2003 Oct 1;57(2):377-83. doi: 10.1016/s0360-3016(03)00573-x.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zapatero A, Guerrero A, Maldonado X, Alvarez A, San-Segundo CG, Rodriguez MAC, Sole JM, Olive AP, Casas F, Boladeras A, de Vidales CM, de la Torre MLV, Vara S, Sanz JL, Calvo FA. High-dose radiotherapy and risk-adapted androgen deprivation in localised prostate cancer (DART 01/05): 10-year results of a phase 3 randomised, controlled trial. Lancet Oncol. 2022 May;23(5):671-681. doi: 10.1016/S1470-2045(22)00190-5. Epub 2022 Apr 12.

Zapatero A, Guerrero A, Maldonado X, Alvarez A, Gonzalez-San Segundo C, Cabeza Rodriguez MA, Macias V, Pedro Olive A, Casas F, Boladeras A, Martin de Vidales C, Vazquez de la Torre ML, Calvo FA. Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial. Int J Radiat Oncol Biol Phys. 2016 Oct 1;96(2):341-348. doi: 10.1016/j.ijrobp.2016.06.2445. Epub 2016 Jun 22.

Zapatero A, Guerrero A, Maldonado X, Alvarez A, Gonzalez San Segundo C, Cabeza Rodriguez MA, Macias V, Pedro Olive A, Casas F, Boladeras A, de Vidales CM, Vazquez de la Torre ML, Villa S, Perez de la Haza A, Calvo FA. High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Mar;16(3):320-7. doi: 10.1016/S1470-2045(15)70045-8. Epub 2015 Feb 19. Erratum In: Lancet Oncol. 2015 Jun;16(6):e262.

• Responsible Party: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• ClinicalTrials.gov Identifier: NCT02175212
• Other Study ID Numbers: DART01/05
• First Submitted: June 23, 2014
• First Posted: June 26, 2014
• Results First Submitted: May 4, 2016
• Results First Posted: November 4, 2016
• Last Update Posted: November 20, 2020