S9921, Hormone Therapy With or Without Mitoxantrone and Prednisone in Patients Who Have Undergone Radical Prostatectomy for Prostate Cancer

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00004124
• Collaborator: National Cancer Institute (NCI) (NIH), Cancer and Leukemia Group B (Other)
• Enrollment: 983
• Locations: 234
• Arms: 2
• Duration (Months): 212
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Hormones can stimulate the production of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy plus mitoxantrone and prednisone is more effective than hormone therapy alone for prostate cancer.

PURPOSE: This randomized phase III trial is studying hormone therapy, mitoxantrone, and prednisone to see how well they work compared to hormone therapy alone in treating patients who have undergone radical prostatectomy for prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: bicalutamide; Drug: goserelin; Drug: mitoxantrone hydrochloride; Drug: prednisone	Phase 3

Detailed Description

OBJECTIVES:

• Compare the overall and disease-free survival of patients with high-risk adenocarcinoma of the prostate treated with adjuvant androgen deprivation therapy with or without mitoxantrone and prednisone after radical prostatectomy.

• Compare the qualitative and quantitative toxic effects of these regimens in this patient population.

• Compare the prostate-specific antigen (PSA) progression-free survival rate in patient treated with these regimens.

• Determine whether PSA progression is a surrogate endpoint for survival or disease-free survival in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to surgical extent of disease (organ confined vs not organ confined, but N0 vs N1), Gleason's sum (less than 7 vs 7 vs greater than 7), and planned radiotherapy (yes vs no). Patients are randomized to one of two treatment arms.

• Arm I:Patients receive goserelin subcutaneously once every 13 weeks (8 injections total) and oral bicalutamide once daily for 2 years in the absence of disease progression or unacceptable toxicity.

• Arm II:Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hormonal therapy as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone.

Patients may undergo radiotherapy 5 days a week for 6.5-7.8 weeks beginning anytime (arm I) or after completion of chemotherapy (arm II), at the discretion of the physician, in the absence of disease progression or unacceptable toxicity.

Patients are offered the possibility to participate in biomarker research by allowing their tissue/blood to be studied.

Patients are followed every 6 months for 2 years and then annually for up to 13 years.

PROJECTED ACCRUAL: A total of 1,360 patients (680 per treatment arm) will be accrued for this study within 9.5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 983 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone Plus Androgen Deprivation in Selected High-Risk Prostate Cancer Patients Following Radical Prostatectomy
• Study Start Date: Oct 1, 1999
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: bicalutamide, goserelin androgen deprivation	Drug: bicalutamide; Other Names: Casodex ; Drug: goserelin; Other Names: Zoladex
Experimental: bicalutamide, goserelin, mitoxantrone, prednisone androgen deprivation plus mitoxantrone, prednisone	Drug: bicalutamide; Other Names: Casodex ; Drug: goserelin; Other Names: Zoladex ; Drug: mitoxantrone hydrochloride; Drug: prednisone

Outcome Measures

Primary Outcome Measures

1. Overall Survival [at 10 Years]

   Measured from date of randomization to date of death from any cause. Patient known to be alive are censored at date of last contact.

2. Disease Free Survival [at 10 Years]

   Measured from date of randomization to date of first observation of recurrence or death due to any cause. Patients without recurrence are censored at date of last contact.

Secondary Outcome Measures

1. Compare Qualitative and Quantitative Toxicities of These Regimens in These Patients [Up to 22 months from registration]

   Number of patients with adverse events that are related to study drug

2. PSA Progression Free Survival [Up to 10 Years]

   Measured from date of randomization to date of PSA progression or death due to any cause. PSA progression is defined as a serum PSA level of > 0.2 ng/mL measured on 3 consecutive occasions or in the absence of increasing PSA, a positive bone scan result or other radiographic or histologic evidence of progression will be used. Date of progression will be the date that the first measure of increasing PSA is noted in the series of 3.

3. PSA Progression as Surrogate Endpoint for Overall Survival or Disease Free Survival [Up to 10 Years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed stage T1-T3 adenocarcinoma of the prostate before radical prostatectomy and lymph node dissection

• Must have undergone prostatectomy within the past 120 days

• Must meet at least 1 of the following pathologic criteria:

• Gleason sum at least 8

• pT3b (seminal vesicle), pT4, or N1

• Gleason sum of 7 and positive margin

• Preoperative PSA greater than 15 ng/mL, Gleason score greater than 7, or PSA level greater than 10 ng/mL and Gleason score greater than 6

• Must have an undetectable PSA (no greater than 0.2 ng/mL) documented after surgery or prior to adjuvant hormonal therapy (for patients initiating adjuvant hormonal therapy prior to study)

• No evidence of metastatic disease on bone scan if PSA is 20 ng/mL or greater at clinical diagnosis

• No distant metastatic disease

PATIENT CHARACTERISTICS:

Performance status:

• SWOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No uncontrolled congestive heart failure

• If history of cardiac disease, LVEF at least 50% by MUGA scan or 2-D echocardiogram

Other:

• No HIV positivity

• No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer that is currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Prior neoadjuvant hormonal therapy of no more than 4 months duration before radical prostatectomy allowed

• Other concurrent adjuvant hormonal therapy allowed if initiated prior to study

• Concurrent low-dose megestrol (less than 40 mg/day) for hot flashes allowed

Radiotherapy:

• No prior radiotherapy

• No concurrent whole pelvis irradiation

• Concurrent radiotherapy allowed at the discretion of the physician

Surgery:

• See Disease Characteristics

• See Endocrine therapy

• Recovered from prior surgery

Other:

• No other prior or concurrent therapy for adenocarcinoma of the prostate

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Regional Hospital Cancer Center	Anchorage	Alaska	United States	99508
2	Providence Cancer Center	Anchorage	Alaska	United States	99508
3	Banner Thunderbird Medical Center	Glendale	Arizona	United States	85306
4	Banner Good Samaritan Medical Center	Phoenix	Arizona	United States	85006
5	CCOP - Western Regional, Arizona	Phoenix	Arizona	United States	85006
6	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
7	Highlands Oncology Group - Springdale	Springdale	Arkansas	United States	72764
8	Alta Bates Comprehensive Cancer Center	Berkeley	California	United States	94704
9	Peninsula Medical Center	Burlingame	California	United States	94010
10	California Cancer Care, Incorporated	Greenbrae	California	United States	94904
11	Marin Cancer Institute at Marin General Hospital	Greenbrae	California	United States	94904
12	Sutter Health - Western Division Cancer Research Group	Greenbrae	California	United States	94904
13	Naval Medical Center - San Diego	San Diego	California	United States	92134
14	San Francisco General Hospital Medical Center	San Francisco	California	United States	94110
15	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
16	California Pacific Medical Center - California Campus	San Francisco	California	United States	94118
17	Veterans Affairs Medical Center - San Francisco	San Francisco	California	United States	94121
18	Cancer Center of Santa Barbara	Santa Barbara	California	United States	93105
19	Sansum Medical Clinic	Santa Barbara	California	United States	93105
20	Santa Barbara Hematology Oncology Medical Group at Cancer Center of Santa Barbara	Santa Barbara	California	United States	93105
21	Santa Barbara Hematology Oncology - Solvang	Solvang	California	United States	93463
22	Sutter Solano Medical Center	Vallejo	California	United States	94589
23	Memorial Hospital	Colorado Springs	Colorado	United States	80909
24	North Colorado Medical Center	Greeley	Colorado	United States	80631
25	McKee Medical Center	Loveland	Colorado	United States	80539
26	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
27	Carl and Dorothy Bennett Cancer Center at Stamford Hospital	Stamford	Connecticut	United States	06904
28	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
29	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912
30	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
31	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
32	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
33	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60507
34	Good Shepherd Hospital	Barrington	Illinois	United States	60010
35	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
36	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
37	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois	United States	60611
38	University of Illinois Cancer Center	Chicago	Illinois	United States	60612-7243
39	Veterans Affairs Medical Center - Chicago Westside Hospital	Chicago	Illinois	United States	60612
40	Mercy Hospital and Medical Center	Chicago	Illinois	United States	60616
41	Swedish Covenant Hospital	Chicago	Illinois	United States	60625
42	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
43	Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Chicago	Illinois	United States	60657
44	Advocate Good Samaritan Hospital	Downers Grove	Illinois	United States	60515
45	Evanston Northwestern Healthcare - Evanston Hospital	Evanston	Illinois	United States	60201-1781
46	Veterans Affairs Medical Center - Hines	Hines	Illinois	United States	60141
47	Midwest Center for Hematology/Oncology	Joliet	Illinois	United States	60432
48	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
49	La Grange Memorial Hospital	La Grange	Illinois	United States	60525
50	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois	United States	60048
51	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
52	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
53	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois	United States	60714
54	Mid-Illinois Hematology-Oncology Associates at Community Cancer Center	Normal	Illinois	United States	61761
55	Cancer Care Center at Advocate Lutheran Hospital	Park Ridge	Illinois	United States	60068
56	Hematology Oncology Associates - Skokie	Skokie	Illinois	United States	60076
57	Hematology/Oncology of the North Shore at Gross Point Medical Center	Skokie	Illinois	United States	60076
58	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
59	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
60	Oncology/Hematology Associates of Southwest Indiana at St. Mary's Cancer Center	Evansville	Indiana	United States	47714
61	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5289
62	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
63	McFarland Clinic, PC	Ames	Iowa	United States	50010
64	St. Luke's Hospital	Cedar Rapids	Iowa	United States	52402
65	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
66	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
67	Cedar Valley Medical Specialists, PC - West Ridgeway Avenue	Waterloo	Iowa	United States	50702
68	Covenant Cancer Treatment Center	Waterloo	Iowa	United States	50702
69	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
70	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
71	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
72	Veterans Affairs Medical Center - Kansas City	Kansas City	Kansas	United States	64128
73	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
74	Southwest Medical Center	Liberal	Kansas	United States	67901
75	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
76	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
77	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
78	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
79	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
80	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67203
81	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
82	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
83	CCOP - Wichita	Wichita	Kansas	United States	67214
84	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
85	Wesley Medical Center	Wichita	Kansas	United States	67214
86	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
87	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0293
88	Louisiana State University Health Sciences Center - Monroe	Monroe	Louisiana	United States	71210
89	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana	United States	71101
90	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana	United States	71130-3932
91	Cancer Research Center at Boston Medical Center	Boston	Massachusetts	United States	02118
92	Lahey Clinic Medical Center - Burlington	Burlington	Massachusetts	United States	01805
93	Commonwealth Hematology-Oncology P.C. - Worcester	Worcester	Massachusetts	United States	01605
94	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
95	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
96	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
97	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
98	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
99	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
100	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
101	Hurley Medical Center	Flint	Michigan	United States	48503
102	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
103	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
104	Spectrum Health Hospital - Butterworth Campus	Grand Rapids	Michigan	United States	49503
105	Metro Health Hospital	Grand Rapids	Michigan	United States	49506
106	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
107	Holland Community Hospital	Holland	Michigan	United States	49423
108	Green Bay Oncology, Limited - Iron Mountain	Iron Mountain	Michigan	United States	49801
109	Foote Hospital	Jackson	Michigan	United States	49201
110	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48909
111	Hackley Hospital	Muskegon	Michigan	United States	49442
112	Northern Michigan Hospital	Petoskey	Michigan	United States	49770
113	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
114	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
115	Seton Cancer Institute - Saginaw	Saginaw	Michigan	United States	48601
116	Munson Medical Center	Traverse City	Michigan	United States	49684
117	St. John Macomb Hospital	Warren	Michigan	United States	48093
118		Alexandria	Minnesota	United States	56308
119	Brainerd Medical Center	Brainerd	Minnesota	United States	56401
120	St. Joseph's Medical Center	Brainerd	Minnesota	United States	56401
121		Fergus Falls	Minnesota	United States	56537
122	Chippewa County - Montevideo Hospital	Montevideo	Minnesota	United States	56265
123	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
124	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
125	Adult and Pediatric Urology, P.L.L.P.	Sartell	Minnesota	United States	56377
126	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63701
127	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Cape Girardeau	Missouri	United States	63701
128	Saint Luke's Hospital	Chesterfield	Missouri	United States	63017
129	CCOP - Kansas City	Kansas City	Missouri	United States	64131
130	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
131	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
132	Arch Medical Services, Incorporated at Center for Cancer Care Research	Saint Louis	Missouri	United States	63141
133	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
134	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
135	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
136	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
137	St. Vincent Healthcare	Billings	Montana	United States	59101
138	Billings Clinic Cancer Center	Billings	Montana	United States	59107-5100
139	Deaconess Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
140	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
141	St. James Community Hospital	Butte	Montana	United States	59701
142	Great Falls Clinic	Great Falls	Montana	United States	59405
143	Sletten Regional Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
144		Great Falls	Montana	United States	59405
145	St. Peter's Hospital	Helena	Montana	United States	59601
146	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
147	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
148	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
149	Community Medical Center	Missoula	Montana	United States	59801
150	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
151	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
152	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
153	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska	United States	68848-1990
154	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
155	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
156	Kingsbury Center for Cancer Care at Cheshire Medical Center	Keene	New Hampshire	United States	03431
157	Lakes Region General Hospital	Laconia	New Hampshire	United States	03246
158	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
159	Elliot Regional Cancer Center at Elliot Hospital	Manchester	New Hampshire	United States	03103
160	Frisbie Memorial Hospital	Rochester	New Hampshire	United States	03867
161	Cancer Institute of New Jersey at Hamilton	Hamilton	New Jersey	United States	08690
162	Mountainside Hospital Cancer Center	Montclair	New Jersey	United States	07042
163	Carol G. Simon Cancer Center at Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
164	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
165	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico	United States	87131-5636
166	Veterans Affairs Medical Center - Brooklyn	Brooklyn	New York	United States	11209
167	Veterans Affairs Medical Center - Buffalo	Buffalo	New York	United States	14215
168	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
169	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
170	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
171	Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
172	Lenoir Memorial Cancer Center	Kinston	North Carolina	United States	28501
173	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
174	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
175	Cancer Care Center at Medcenter One Hospital	Bismarck	North Dakota	United States	58501
176	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
177	St. Alexius Medical Center	Bismarck	North Dakota	United States	58502
178	Akron City Hospital	Akron	Ohio	United States	44309-2090
179	Community Hospitals and Wellness Centers - Bryan	Bryan	Ohio	United States	43506
180	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
181	Community Oncology Group at Cleveland Clinic Cancer Center	Independence	Ohio	United States	44131
182	St. Rita's Medical Center	Lima	Ohio	United States	45801
183	Cleveland Clinic - Wooster	Wooster	Ohio	United States	44691
184	Tod Children's Hospital - Forum Health	Youngstown	Ohio	United States	44501
185	OU Cancer Institute	Oklahoma City	Oklahoma	United States	73104
186	St. Charles Medical Center - Bend	Bend	Oregon	United States	97701
187	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
188	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
189	Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center	Portland	Oregon	United States	97210
190	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
191	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
192	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
193	Legacy Emanuel Hospital and Health Center & Children's Hospital	Portland	Oregon	United States	97227
194	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
195	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
196	PinnacleHealth Regional Cancer Center at Polyclinic Hospital	Harrisburg	Pennsylvania	United States	17105
197	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
198	Cancer Care Institute of Carolina at Aiken Regional Medical Centers	Aiken	South Carolina	United States	29801
199	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
200	Roper St. Francis Cancer Center at Roper Hospital	Charleston	South Carolina	United States	29401
201	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
202	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
203	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
204	Mountainview Medical	Berlin	Vermont	United States	05602
205	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
206	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
207	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
208	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington	United States	98273
209	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98104
210	Harborview Medical Center	Seattle	Washington	United States	98104
211	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
212	Group Health Central Hospital	Seattle	Washington	United States	98112
213	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
214	Polyclinic First Hill	Seattle	Washington	United States	98122
215	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043
216	North Puget Oncology at United General Hospital	Sedro-Woolley	Washington	United States	98284
217	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
218	Rockwood Clinic Cancer Treatment Center	Spokane	Washington	United States	99204-2967
219	Madigan Army Medical Center - Tacoma	Tacoma	Washington	United States	98431
220	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
221	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028
222	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
223	Fox Valley Hematology and Oncology - East Grant Street	Appleton	Wisconsin	United States	54911-3496
224	Green Bay Oncology, Limited at St. Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
225	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
226	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
227	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
228	Dean Medical Center - Madison	Madison	Wisconsin	United States	53717
229	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
230	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
231	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
232	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
233	University of Wisconcin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin	United States	54401
234	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)
• Cancer and Leukemia Group B

Investigators

• Study Chair: L. Michael Glode, MD, University of Colorado, Denver
• Study Chair: Nancy A. Dawson, MD, University of Maryland Greenebaum Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 15, 2015

More Information

Additional Information:

• SWOG Cancer Research Network website

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00004124
• Other Study ID Numbers: CDR0000067352; S9921; CALGB-99904; U10CA032102
• First Posted: Jan 27, 2003
• Last Update Posted: Jun 14, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Southwest Oncology Group: adenocarcinoma of the prostate; stage I prostate cancer; stage II prostate cancer; stage III prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Prednisone; Goserelin; Mitoxantrone; Bicalutamide

Study Results

Participant Flow

Recruitment Details	983 patients consented and were enrolled to the trial. 22 patients were found to be ineligible per eligibility criteria, and were thus excluded from final analysis.

Arm/Group Title	Arm I: Bicalutamide + Goserelin	Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin
Arm/Group Description	Patients receive goserelin subcutaneously once every 13 weeks (8 injections total) and oral bicalutamide once daily for 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hormonal therapy as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone.
Period Title: Overall Study
STARTED	481	480
COMPLETED	469	460
NOT COMPLETED	12	20

Baseline Characteristics

Arm/Group Title	Arm I: Bicalutamide + Goserelin	Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin	Total
Arm/Group Description	Patients receive goserelin subcutaneously once every 13 weeks (8 injections total) and oral bicalutamide once daily for 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hormonal therapy as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone.	Total of all reporting groups
Overall Participants	481	480	961
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60	60	60
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	481 100%	480 100%	961 100%
Race/Ethnicity, Customized (Count of Participants)
White	399 83%	411 85.6%	810 84.3%
Black	66 13.7%	50 10.4%	116 12.1%
Asian	6 1.2%	11 2.3%	17 1.8%
Other	10 2.1%	8 1.7%	18 1.9%
PSA at Prostatectomy (ng/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ng/mL]	7.9	7.4	7.7
Hispanic (Count of Participants)
Count of Participants [Participants]	25 5.2%	30 6.3%	55 5.7%
Disease Extent (Count of Participants)
N1	79 16.4%	83 17.3%	162 16.9%
>= T3 but N0	293 60.9%	306 63.8%	599 62.3%
Organ Confined	109 22.7%	91 19%	200 20.8%
Positive Margins from Prostatectomy (Count of Participants)
Count of Participants [Participants]	316 65.7%	293 61%	609 63.4%
Intent to Receive Adjuvant RT (Count of Participants)
Count of Participants [Participants]	130 27%	127 26.5%	257 26.7%
Gleason Score (Count of Participants)
<= 6	10 2.1%	12 2.5%	22 2.3%
7	215 44.7%	220 45.8%	435 45.3%
8 - 10	256 53.2%	248 51.7%	504 52.4%
Risk Groups (Count of Participants)
Node Positive	79 16.4%	83 17.3%	162 16.9%
Gleason Score >= 8 or pT3b	276 57.4%	296 61.7%	572 59.5%
Gleason Score<8 w/Positive Margins or PSA>10 ng/mL	126 26.2%	101 21%	227 23.6%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Measured from date of randomization to date of death from any cause. Patient known to be alive are censored at date of last contact.
Time Frame	at 10 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I: Bicalutamide + Goserelin	Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin
Arm/Group Description	Patients receive goserelin subcutaneously once every 13 weeks (8 injections total) and oral bicalutamide once daily for 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hormonal therapy as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone.
Measure Participants	481	480
Number [percentage of probability of survival]	87	86

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: Bicalutamide + Goserelin, Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Disease Free Survival
Description	Measured from date of randomization to date of first observation of recurrence or death due to any cause. Patients without recurrence are censored at date of last contact.
Time Frame	at 10 Years

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Arm I: Bicalutamide + Goserelin	Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin
Arm/Group Description	Patients receive goserelin subcutaneously once every 13 weeks (8 injections total) and oral bicalutamide once daily for 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hormonal therapy as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone.
Measure Participants	480	481
Number [percentage of probability of survival]	72	72

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: Bicalutamide + Goserelin, Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Compare Qualitative and Quantitative Toxicities of These Regimens in These Patients
Description	Number of patients with adverse events that are related to study drug
Time Frame	Up to 22 months from registration

Outcome Measure Data

Analysis Population Description

All eligible patients who received protocol therapy

Arm/Group Title	Arm I: Bicalutamide + Goserelin	Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin
Arm/Group Description	Patients receive goserelin subcutaneously once every 13 weeks (8 injections total) and oral bicalutamide once daily for 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hormonal therapy as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone.
Measure Participants	469	460
Abdominal pain/cramping	19 4%	41 8.5%
Abscess	0 0%	1 0.2%
Alkaline phosphatase increase	11 2.3%	11 2.3%
Allergic reaction	1 0.2%	5 1%
Allergic rhinitis	2 0.4%	16 3.3%
Alopecia	91 18.9%	131 27.3%
Anal incontinence	2 0.4%	2 0.4%
Anemia	52 10.8%	141 29.4%
Anorexia	7 1.5%	41 8.5%
Anxiety/agitation	52 10.8%	62 12.9%
Apnea	1 0.2%	1 0.2%
Arrhythmia, NOS	0 0%	1 0.2%
Arthralgia	43 8.9%	64 13.3%
Arthritis	17 3.5%	17 3.5%
Ataxia (incoordination)	1 0.2%	1 0.2%
Bilirubin increase	5 1%	20 4.2%
Blurred vision	3 0.6%	6 1.3%
Bone pain	19 4%	34 7.1%
Bruising	1 0.2%	14 2.9%
CPK increase	0 0%	2 0.4%
Cardiac ischemia/infarction	1 0.2%	1 0.2%
Cardiovascular-other	0 0%	5 1%
Cataract	5 1%	6 1.3%
Cerebrovascular ischemia	1 0.2%	0 0%
Chest pain,not cardio or pleur	11 2.3%	19 4%
Conduction abnormality/block	1 0.2%	0 0%
Confusion	6 1.2%	14 2.9%
Conjunctivitis	0 0%	4 0.8%
Constipation/bowel obstruction	57 11.9%	117 24.4%
Cough	10 2.1%	34 7.1%
Creatinine increase	7 1.5%	17 3.5%
Cushingoid appearance	0 0%	8 1.7%
Dehydration	0 0%	6 1.3%
Depression	80 16.6%	85 17.7%
Diarrhea without colostomy	55 11.4%	75 15.6%
Dizziness/light headedness	33 6.9%	71 14.8%
Dry eye	1 0.2%	5 1%
Dry skin	11 2.3%	28 5.8%
Dysmenorrhea	0 0%	1 0.2%
Dyspepsia/heartburn	7 1.5%	44 9.2%
Dyspnea	21 4.4%	49 10.2%
Dysuria	14 2.9%	11 2.3%
Ear-other	0 0%	2 0.4%
Edema	40 8.3%	56 11.7%
Endocrine-other	3 0.6%	2 0.4%
Epistaxis	0 0%	2 0.4%
Erectile impotence	181 37.6%	146 30.4%
Eryth/rash/eruption/desq, NOS	0 0%	2 0.4%
Esophagitis/dysphagia	2 0.4%	13 2.7%
Eye-other	1 0.2%	6 1.3%
Fatigue/malaise/lethargy	258 53.6%	357 74.4%
Febrile neutropenia	0 0%	2 0.4%
Feminization of male	1 0.2%	0 0%
Fever without neutropenia	0 0%	9 1.9%
Fever, NOS	1 0.2%	6 1.3%
Flatulence	2 0.4%	3 0.6%
Flu-like symptoms-other	2 0.4%	6 1.3%
Flushing	5 1%	4 0.8%
GGT increase	1 0.2%	0 0%
GI Mucositis, NOS	0 0%	10 2.1%
GI-other	12 2.5%	20 4.2%
GU-other	9 1.9%	9 1.9%
Gastritis	2 0.4%	0 0%
Gastritis/ulcer, NOS	0 0%	1 0.2%
Glaucoma	2 0.4%	0 0%
Gynecomastia	140 29.1%	100 20.8%
Headache	37 7.7%	82 17.1%
Hematologic-other	1 0.2%	1 0.2%
Hematuria	9 1.9%	13 2.7%
Hemolysis	0 0%	1 0.2%
Hemoptysis	0 0%	1 0.2%
Hemorrhage-other	1 0.2%	4 0.8%
Hiccoughs	0 0%	4 0.8%
Hot flashes	439 91.3%	422 87.9%
Hypercalcemia	4 0.8%	5 1%
Hypercholesterolemia	5 1%	2 0.4%
Hyperglycemia	44 9.1%	78 16.3%
Hyperkalemia	0 0%	4 0.8%
Hypermagnesemia	0 0%	1 0.2%
Hypernatremia	0 0%	4 0.8%
Hypertension	38 7.9%	38 7.9%
Hypertriglyceridemia	2 0.4%	0 0%
Hypoalbuminemia	1 0.2%	6 1.3%
Hypocalcemia	1 0.2%	7 1.5%
Hypoglycemia	0 0%	1 0.2%
Hypokalemia	8 1.7%	11 2.3%
Hypomagnesemia	1 0.2%	1 0.2%
Hyponatremia	3 0.6%	2 0.4%
Hypotension	3 0.6%	11 2.3%
Hypothyroidism	2 0.4%	0 0%
Hypoxia	0 0%	4 0.8%
Incontinence	88 18.3%	71 14.8%
Infection w/o 3-4 neutropenia	5 1%	10 2.1%
Infection with 3-4 neutropenia	0 0%	2 0.4%
Infection, unk ANC	1 0.2%	4 0.8%
Inner ear-hearing loss	3 0.6%	2 0.4%
Insomnia	79 16.4%	92 19.2%
Invol. movement/restlessness	2 0.4%	2 0.4%
Joint,muscle,bone-other	11 2.3%	27 5.6%
LVEF decrease/CHF	0 0%	8 1.7%
Leukopenia	14 2.9%	317 66%
Libido loss	163 33.9%	133 27.7%
Local injection site reaction	11 2.3%	17 3.5%
Lung-other	0 0%	2 0.4%
Lymphopenia	4 0.8%	49 10.2%
Male infertility	2 0.4%	3 0.6%
Melena/ GI bleeding	0 0%	2 0.4%
Memory loss	15 3.1%	12 2.5%
Metabolic-other	0 0%	1 0.2%
Middle ear-hearing loss/otitis	0 0%	1 0.2%
Mood/consciousness change, NOS	2 0.4%	3 0.6%
Mouth dryness	10 2.1%	13 2.7%
Muscle weakness (not neuro)	55 11.4%	77 16%
Myalgia	26 5.4%	45 9.4%
Myalgia/arthralgia, NOS	1 0.2%	12 2.5%
Myocarditis	0 0%	1 0.2%
Nail changes	4 0.8%	57 11.9%
Nausea	26 5.4%	205 42.7%
Neuro-other	5 1%	4 0.8%
Neuropathic pain	0 0%	1 0.2%
Neutropenia/granulocytopenia	11 2.3%	239 49.8%
PRBC transfusion	0 0%	3 0.6%
Pain-other	112 23.3%	127 26.5%
Palpitations	1 0.2%	6 1.3%
Pelvic pain	9 1.9%	11 2.3%
Pericar. effusion/pericarditis	0 0%	1 0.2%
Personality/behavioral change	12 2.5%	11 2.3%
Phlebitis	0 0%	5 1%
Pigmentation changes/yellowing	0 0%	3 0.6%
Pleural effusions	0 0%	1 0.2%
Pneumonitis/infiltrates	0 0%	1 0.2%
Proctitis	4 0.8%	4 0.8%
Proteinuria	3 0.6%	1 0.2%
Pruritus	13 2.7%	23 4.8%
RT-GI mucositis, NOS	0 0%	1 0.2%
RT-focal dermatitis, NOS	3 0.6%	1 0.2%
RT-late bladder morbidity	1 0.2%	0 0%
RT-late intestinal morbidity	2 0.4%	1 0.2%
RT-pain	1 0.2%	0 0%
Rash/desquamation	46 9.6%	63 13.1%
Rectal bleeding/hematochezia	12 2.5%	10 2.1%
Rectal/perirectal pain	7 1.5%	5 1%
Respiratory infect w/o neutrop	1 0.2%	7 1.5%
Respiratory infection, unk ANC	1 0.2%	8 1.7%
Rigors/chills	7 1.5%	24 5%
SGOT (AST) increase	42 8.7%	42 8.8%
SGPT (ALT) increase	22 4.6%	26 5.4%
Salivary change, NOS	0 0%	1 0.2%
Second primary	0 0%	6 1.3%
Seizures	1 0.2%	1 0.2%
Sensory neuropathy	37 7.7%	57 11.9%
Sexual/reproductive-other	2 0.4%	1 0.2%
Sinus bradycardia	0 0%	4 0.8%
Skin-other	11 2.3%	11 2.3%
Speech impairment	0 0%	1 0.2%
Stomatitis/pharyngitis	5 1%	49 10.2%
Supraventricular arrhythmia	0 0%	2 0.4%
Surgery-wound infection	0 0%	1 0.2%
Sweating	138 28.7%	129 26.9%
Syncope	0 0%	3 0.6%
Taste disturbance	1 0.2%	46 9.6%
Tearing	0 0%	6 1.3%
Thrombocytopenia	3 0.6%	35 7.3%
Thrombosis/embolism	2 0.4%	5 1%
Tremor	0 0%	2 0.4%
Troponin T (cTnT) increase	0 0%	1 0.2%
Urinary frequency/urgency	86 17.9%	101 21%
Urinary retention	13 2.7%	7 1.5%
Urinary tr infect w/ neutrop	0 0%	1 0.2%
Urinary tr infect w/o neutrop	1 0.2%	2 0.4%
Urinary tr infection, unk ANC	3 0.6%	2 0.4%
Urine color change	3 0.6%	44 9.2%
Urticaria	3 0.6%	4 0.8%
Ventricular arrhythmia	1 0.2%	0 0%
Vertigo	1 0.2%	1 0.2%
Vision,NOS	0 0%	1 0.2%
Voice change/stridor/larynx	0 0%	6 1.3%
Vomiting	10 2.1%	51 10.6%
Weakness (motor neuropathy)	3 0.6%	6 1.3%
Weight gain	179 37.2%	151 31.5%
Weight loss	12 2.5%	29 6%

4. Secondary Outcome

Title	PSA Progression Free Survival
Description	Measured from date of randomization to date of PSA progression or death due to any cause. PSA progression is defined as a serum PSA level of > 0.2 ng/mL measured on 3 consecutive occasions or in the absence of increasing PSA, a positive bone scan result or other radiographic or histologic evidence of progression will be used. Date of progression will be the date that the first measure of increasing PSA is noted in the series of 3.
Time Frame	Up to 10 Years

Outcome Measure Data

Analysis Population Description

Data for trial not collected for analysis.

Arm/Group Title	Arm I: Bicalutamide + Goserelin	Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin
Arm/Group Description	Patients receive goserelin subcutaneously once every 13 weeks (8 injections total) and oral bicalutamide once daily for 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hormonal therapy as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone.
Measure Participants	0	0

5. Secondary Outcome

Title	PSA Progression as Surrogate Endpoint for Overall Survival or Disease Free Survival
Time Frame	Up to 10 Years

Outcome Measure Data

Analysis Population Description

Data not collected for analysis.

Arm/Group Title	Arm I: Bicalutamide + Goserelin	Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin
Arm/Group Description	Patients receive goserelin subcutaneously once every 13 weeks (8 injections total) and oral bicalutamide once daily for 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hormonal therapy as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone.
Measure Participants	0	0

Adverse Events

Time Frame	Arm 1 assessed every 3 months up through 22 months; Arm 2 assessed every 21 days through first four months, and then every 3 months through 22 months
Adverse Event Reporting Description	Patients on Arm 1 were monitored for toxicity every 3 months while on hormonal therapy. Patients on Arm 2 were monitored every 21 days while receiving chemotherapy in first 4 months of study, and then every 3 months through hormonal therapy. Patients on either arm maybe have had more frequent monitoring at discretion of the treating physician.
Arm/Group Title	Arm I: Bicalutamide + Goserelin		Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin
Arm/Group Description	Patients receive goserelin subcutaneously once every 13 weeks (8 injections total) and oral bicalutamide once daily for 2 years in the absence of disease progression or unacceptable toxicity.		Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hormonal therapy as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone.
All Cause Mortality
	Arm I: Bicalutamide + Goserelin		Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/469 (18.1%)		91/460 (19.8%)
Serious Adverse Events
	Arm I: Bicalutamide + Goserelin		Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/469 (0.6%)		11/460 (2.4%)
Cardiac disorders
Cardiac ischemia/infarction	0/469 (0%)		1/460 (0.2%)
General disorders
Reportable adverse event, NOS	1/469 (0.2%)		0/460 (0%)
Flu-like symptoms-other	1/469 (0.2%)		2/460 (0.4%)
Pain-other	0/469 (0%)		1/460 (0.2%)
Infections and infestations
Infection with 3-4 neutropenia	0/469 (0%)		2/460 (0.4%)
Metabolism and nutrition disorders
Hyperglycemia	0/469 (0%)		1/460 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Second primary	1/469 (0.2%)		5/460 (1.1%)
Vascular disorders
Thrombosis/embolism	0/469 (0%)		1/460 (0.2%)
Other (Not Including Serious) Adverse Events
	Arm I: Bicalutamide + Goserelin		Arm II: Mitoxantrone + Prednisone + Bivalutamid + Goserelin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	461/469 (98.3%)		457/460 (99.3%)
Blood and lymphatic system disorders
Anemia	71/469 (15.1%)		152/460 (33%)
Cardiac disorders
Edema	50/469 (10.7%)		65/460 (14.1%)
Hypertension	58/469 (12.4%)		51/460 (11.1%)
Endocrine disorders
Gynecomastia	140/469 (29.9%)		100/460 (21.7%)
Hot flashes	440/469 (93.8%)		422/460 (91.7%)
Gastrointestinal disorders
Constipation/bowel obstruction	69/469 (14.7%)		133/460 (28.9%)
Diarrhea without colostomy	62/469 (13.2%)		87/460 (18.9%)
Dyspepsia/heartburn	11/469 (2.3%)		44/460 (9.6%)
GI-other	17/469 (3.6%)		25/460 (5.4%)
Nausea	31/469 (6.6%)		210/460 (45.7%)
Stomatitis/pharyngitis	7/469 (1.5%)		49/460 (10.7%)
Taste disturbance	1/469 (0.2%)		46/460 (10%)
Vomiting	16/469 (3.4%)		54/460 (11.7%)
Abdominal pain/cramping	30/469 (6.4%)		53/460 (11.5%)
General disorders
Fatigue/malaise/lethargy	268/469 (57.1%)		365/460 (79.3%)
Rigors/chills	9/469 (1.9%)		24/460 (5.2%)
Sweating	139/469 (29.6%)		133/460 (28.9%)
Chest pain,not cardio or pleur	16/469 (3.4%)		23/460 (5%)
Pain-other	162/469 (34.5%)		173/460 (37.6%)
Investigations
Leukopenia	20/469 (4.3%)		319/460 (69.3%)
Lymphopenia	8/469 (1.7%)		51/460 (11.1%)
Neutropenia/granulocytopenia	13/469 (2.8%)		240/460 (52.2%)
Thrombocytopenia	7/469 (1.5%)		36/460 (7.8%)
Weight gain	186/469 (39.7%)		153/460 (33.3%)
Weight loss	17/469 (3.6%)		30/460 (6.5%)
SGOT (AST) increase	43/469 (9.2%)		51/460 (11.1%)
SGPT (ALT) increase	24/469 (5.1%)		33/460 (7.2%)
Creatinine increase	10/469 (2.1%)		24/460 (5.2%)
Metabolism and nutrition disorders
Anorexia	9/469 (1.9%)		44/460 (9.6%)
Hyperglycemia	61/469 (13%)		102/460 (22.2%)
Musculoskeletal and connective tissue disorders
Arthritis	30/469 (6.4%)		32/460 (7%)
Joint,muscle,bone-other	17/469 (3.6%)		34/460 (7.4%)
Muscle weakness (not neuro)	58/469 (12.4%)		83/460 (18%)
Arthralgia	57/469 (12.2%)		77/460 (16.7%)
Bone pain	24/469 (5.1%)		34/460 (7.4%)
Myalgia	29/469 (6.2%)		49/460 (10.7%)
Nervous system disorders
Dizziness/light headedness	42/469 (9%)		78/460 (17%)
Sensory neuropathy	59/469 (12.6%)		72/460 (15.7%)
Headache	45/469 (9.6%)		88/460 (19.1%)
Psychiatric disorders
Anxiety/agitation	59/469 (12.6%)		70/460 (15.2%)
Depression	95/469 (20.3%)		99/460 (21.5%)
Insomnia	93/469 (19.8%)		105/460 (22.8%)
Renal and urinary disorders
Incontinence	137/469 (29.2%)		117/460 (25.4%)
Urinary frequency/urgency	131/469 (27.9%)		130/460 (28.3%)
Urine color change	4/469 (0.9%)		44/460 (9.6%)
Reproductive system and breast disorders
Erectile impotence	217/469 (46.3%)		171/460 (37.2%)
Libido loss	168/469 (35.8%)		134/460 (29.1%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	6/469 (1.3%)		23/460 (5%)
Cough	24/469 (5.1%)		46/460 (10%)
Dyspnea	35/469 (7.5%)		59/460 (12.8%)
Skin and subcutaneous tissue disorders
Alopecia	93/469 (19.8%)		133/460 (28.9%)
Dry skin	17/469 (3.6%)		32/460 (7%)
Nail changes	4/469 (0.9%)		59/460 (12.8%)
Pruritus	19/469 (4.1%)		27/460 (5.9%)
Rash/desquamation	59/469 (12.6%)		73/460 (15.9%)

Limitations/Caveats

[Not Specified]

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.