`
`Urol Int 2002;68:10–15
`
`Received: September 19, 2000
`Accepted: April 20, 2001
`
`Prostate-Specific Antigen Levels and Prognosis
`in Patients with Hormone-Refractory Prostate
`Cancer Treated with Low-Dose Dexamethasone
`
`Masaaki Morioka Tatsuya Kobayashi Yoji Furukawa Yoshimasa Jo
`Masanori Shinkai Takakazu Matsuki Tokunori Yamamoto
`Hiroyoshi Tanaka
`
`Department of Urology, Kawasaki Medical School, Kurashiki, Japan
`
`173.72.4.37 - 1/4/2017 6:35:02 PM
`Downloaded by: B. Hare - 405798
`
`Key Words
`Hormone-refractory prostate cancer W Dexamethasone W
`Prostate-specific antigen response W Palliative effect
`
`Abstract
`Objective: The efficacy of low-dose dexamethasone
`(DXM) therapy in patients with hormone-refractory pros-
`tate cancer (HRPC) was evaluated. Patients and Meth-
`ods: Prostate-specific antigen (PSA) response and sur-
`vival following DXM therapy were analyzed in 27 Japa-
`nese patients exhibiting HRPC. Concurrent therapies and
`antiandrogen withdrawal syndrome, which may affect
`PSA levels and palliative effects, were excluded from the
`study. A dose of 1.5 mg of DXM was administered, and
`androgen deprivation therapy was maintained during
`DXM therapy. A decline in PSA levels of at least 50%
`from baseline was considered a significant PSA re-
`sponse. Prognostic factors for PSA response and surviv-
`al were examined by univariate and multivariate analy-
`ses. Results: A significant PSA response was observed in
`16 of the 27 cases (59.3%). Median survival period of
`patients exhibiting significant PSA response was 15.9
`months and was significantly longer than that of patients
`demonstrating a decline in PSA of less than 50% (median
`7.7 months, p ! 0.0001). Effect on pain control also corre-
`
`lated with the significant PSA response. No meaningful
`prognostic factors for PSA response were detected; how-
`ever, a PSA decline of greater than 50% was the prog-
`nostic factor for survival. Conclusion: DXM therapy re-
`mains one of the most beneficial treatment modalities in
`patients with HRPC.
`
`Copyright © 2002 S. Karger AG, Basel
`
`Introduction
`
`Hormone-refractory prostate cancer (HRPC) com-
`prises a heterogeneous group of patients. Clinical re-
`sponses to second-line hormonal manipulations usually
`vary in this group of patients [1, 2]. Combined androgen
`blockade (CAB), antiandrogen withdrawal syndrome
`(AWS), estramustine phosphate (EMP), adrenal androgen
`inhibitors and glucocorticoids are indicated in patients
`with HRPC as second-line hormonal therapies [1, 2]. In
`recent years, new regimens, such as the combination of
`glucocorticoid and mitoxantrone [3, 4] and of EMP and
`docetaxel [5, 6], have been evaluated. Among these treat-
`ment options, glucocorticoid therapy has been shown to
`be an advantageous treatment modality due to its consid-
`erable prostate-specific antigen (PSA) response and pal-
`liative effects. Several reports have been published de-
`
`ABC
`
`Fax + 41 61 306 12 34
`E-Mail karger@karger.ch
`www.karger.com
`
`© 2002 S. Karger AG, Basel
`0042–1138/02/0681–0010$18.50/0
`
`Accessible online at:
`www.karger.com/journals/uin
`
`Masaaki Morioka, MD
`Department of Urology, Kawasaki Medical School
`577 Matsushima
`Kurashiki 701-0192 (Japan)
`Tel. +81 86 462 1111, Fax +81 86 462 1199, E-Mail moriokam@med.kawasaki-m.ac.jp
`
`Amerigen Exhibit 1122
`Amerigen v. Janssen IPR2016-00286
`
`
`
`scribing the clinical effects of hydrocortisone, prednisone
`and dexamethasone (DXM) [7–11]. However, there have
`been few studies in which complicating factors, including
`AWS or external beam radiotherapy (EBR) that may
`potentially affect serum PSA levels and/or palliative ef-
`fects, were excluded. In the present study, the effects of
`low-dose DXM in patients with HRPC were examined in
`terms of PSA decline, survival and improvement of pain
`scale as end points.
`
`Patients and Methods
`
`Between August 1997 and November 1999, 34 patients who had
`failed to prior hormonal therapies, such as androgen deprivation
`therapy using LHRH agonist (goserelin acetate), CAB (goserelin plus
`flutamide) or EMP, were treated with low-dose DXM in our insti-
`tute. Twenty-seven of the 34 cases met the following criteria and were
`
`included in the study: (1) patients presenting with hormone-refracto-
`ry metastatic prostate cancer which had failed to respond to prior
`hormonal therapies; (2) concurrent therapies, including whole pel-
`vis radiation or systemic chemotherapy were not performed, and
`(3) AWS influences were excluded at the initiation of DXM therapy.
`In order to confirm AWS, DXM therapy was initiated following the
`repeated measurements of serum PSA after the discontinuation of
`flutamide. At least two measurements were made, separated by at
`least 2 weeks. AWS was observed in 1 of the 27 cases displaying a
`PSA decline of greater than 50% over 3 months. Serum PSA levels
`were measured by the Tandem-R assay. DXM was administered at a
`total dose of 1.5 mg/day (1 mg morning, 0.5 mg evening). The dosage
`was decreased to 1 mg/day over the 3 months following initiation of
`the therapy. Androgen deprivation therapy (ADT), utilizing gosere-
`lin acetate, was maintained during DXM administration. Serum
`PSA levels and Eastern Cooperative Oncology Group (ECOG) pain
`scale [12] were evaluated every 4–8 weeks. PSA responses were calcu-
`lated as maximum decrease from baseline, and decreases in serum
`PSA levels of greater than 50% were considered as significant
`responses. Biochemical (PSA) failure to DXM therapy was defined as
`
`Table 1. Prior treatments and background
`factors in patients treated with DXM
`
`Background
`
`Age at initial diagnosis, years old
`PSA at initial diagnosis, ng/ml
`Gleason sum
`Time-to-PSA failure in first-line hormone
`therapy, months
`Time-to-initiating DXM therapy from
`initial diagnosis, months
`
`Prior treatments
`
`Range (median), n = 27
`
`56–88 (71)
`18.0–3,100 (388.0)
`5–9 (7)
`2.7–48.9 (11.7), average 14.9
`(95% CI, 10.7–19.1)
`6.6–66.0 (22.4), average 28.0
`(95% CI, 21.8–34.1)
`
`first-line
`
`second-line
`
`third-line
`
`fourth-line
`
`LHRH
`
`10
`
`CAB
`CAB+EBR
`EMP
`EMP+EBR
`DXM
`CTb+EBR
`
`CAB
`
`15
`
`EMP
`
`EMP+EBR
`DXM
`EBR
`
`LHRH + CTa
`
`2
`
`CAB
`
`3 (2)
`1 (1)
`2 (2)
`1 (0)
`2 (2)
`1 (1)
`
`9 (3)
`
`1 (0)
`4 (3)
`1 (0)
`
`2 (1)
`
`DXM
`DXM
`DXM
`DXM
`
`EMP
`
`DXM
`CTb
`DXM
`
`3 (3)
`1 (0)
`2 (1)
`1 (0)
`
`1 (0)
`
`8 (4)
`1 (1)
`1 (0)
`
`DXM
`
`1 (0)
`
`DXM
`EMP+EBR
`
`1 (1)
`1 (0)
`
`DXM 1 (0)
`
`DXM 1 (1)
`
`DXM 1 (1)
`
`LHRH = LHRH agonist (goserelin); CAB = combined androgen blockade (goserelin +
`flutamide); CTa = systemic chemotherapy using vincristine, ifosphamide, peplomycin; CTb =
`CDDP, ifosphamide, epirubicin; EMP = estramustine phosphate; DXM = dexamethasone;
`EBR = external beam radiotherapy for whole pelvis (54–63 Gy).
`Numbers in parentheses show patients in whom PSA decline of greater than 50% was
`observed.
`
`173.72.4.37 - 1/4/2017 6:35:02 PM
`Downloaded by: B. Hare - 405798
`
`Dexamethasone Therapy in Patients with
`Hormone-Refractory Prostate Cancer
`
`Urol Int 2002;68:10–15
`
`11
`
`
`
`was used as second-, third- or fourth-line hormone thera-
`py in 6, 18 and 3 cases, respectively. Eight of 27 patients
`underwent combined endocrine treatment or systemic
`chemotherapy and EBR. However, these therapies were
`not concurrently performed during DXM therapy (ta-
`ble 1).
`At initiation of DXM therapy, median PSA level was
`75 ng/ml (range 5.5–639 ng/ml) and median extent of dis-
`ease (EOD) score was 3 (range 1–4). Maximum PSA
`decline from baseline varied from 0 to 98.7%. Average
`PSA decline was 52.2% (95% CI, 37.1–67.3%). Of the 27
`cases, 16 (59.3%) exhibited a PSA decline of at least 50%.
`Eleven of the 16 cases achieved a PSA decline of at least
`80%. No PSA decline was observed in 6 cases (22.2%)
`whereas 4 patients (14.8%) achieved a PSA decline of less
`than 25%. The remaining patient displayed a PSA decline
`of between 25 and 50%. Nadir PSA levels ranged from 0.1
`to 639 ng/ml (median 28.8). Normal levels were restored
`(!4 ng/ml) in 7 of the 27 cases (25.9%). Median period to
`PSA nadir was 14 weeks (range 2–76), and median
`response duration to DXM evaluated by PSA levels was
`5.4 months. Median survival after DXM therapy was 13.1
`months (average 14.3, 95% CI 11.4–17.2 months). Over-
`all follow-up period from the initial diagnosis was 13.6–
`94.7 months (median 40) (table 2). The correlation be-
`tween PSA response and survival period after DXM ther-
`apy was apparent. That is, median survival of patients
`displaying a PSA decline of at least 50% was 15.9 months
`(n = 16, average 17.9, 95% CI 14.4–21.4 months). In con-
`trast, the median survival of patients achieving a PSA
`decline of less than 50% was 7.7 months (n = 11, average
`9.1, 95% CI 5.9–12.3 months). A significant difference
`was observed between the two groups of patients (p !
`0.0001, log-rank). However, there were no significant dif-
`ferences between the patient groups exhibiting PSA de-
`cline of greater than or less than 80% (p = 0.0728, log-
`rank) (fig. 1).
`Analgesic medication was required in 21 of the 27
`patients (77.8%). Narcotic analgesics (morphine sulfate)
`and non-steroidal anti-inflammatory drugs (NSAIDs)
`were administered in 9 and 12 patients, respectively,
`prior to DXM therapy. Five of the 9 cases became free
`from narcotics for a median period of 10.6 months. Six of
`the 12 cases became free from analgesic medication for a
`median period of 14 months. A close correlation between
`significant PSA response and pain improvement was
`observed. That is, 8 of the 11 cases (72.7%) with favorable
`pain control demonstrated a PSA decline of greater than
`50% (p = 0.0299, ¯2).
`
`Fig. 1. Cause-specific survival rate following DXM therapy. Median
`survival period in patients who achieved a PSA decline of greater
`than 50% was 15.9 months. On the other hand, that in patients with a
`PSA decline of less than 50% was only 7.7 months. Two-year survival
`rate in these groups was 66 and 0%, respectively. The significant dif-
`ference was seen between the two groups by log-rank test.
`
`an increase in PSA levels of greater than 50% from nadir PSA levels
`on repeated measurements [13, 14]. Palliative effects were evaluated
`by ECOG pain scale [12]. An improvement of greater than one grade
`was considered meaningful. The correlation between significant PSA
`response, survival and background factors, including Gleason sum,
`response duration to first-line hormonal therapies and prior treat-
`ments, were analyzed by univariate (¯2 test) and multivariate (Cox
`proportional hazards model) analyses.
`
`Results
`
`Twenty-seven patients were included in this evalua-
`tion. Patient characteristics and prior treatments are sum-
`marized in table 1. LHRH agonist, CAB and LHRH ago-
`nist plus systemic chemotherapy were employed as first-
`line therapies in 10, 15 and 2 cases, respectively. Time-
`to-PSA failure in first-line therapy ranged from 2.7 to 48.9
`months (median 11.7). Time-to-initiation of DXM thera-
`py from initial diagnosis ranged from 6.6 to 66.0 months
`(median 22.4). CAB, EMP or DXM was used as second-
`line therapies in 9 patients failing to respond to ADT. One
`patient underwent the combination of chemotherapy and
`EBR to whole pelvis. PSA response (greater than 50%
`decline) to second-line hormonal treatments was ob-
`served in 7 of the 9 cases (77.8%). In 10 of 15 cases dis-
`playing failure of first-line CAB therapy, EMP was em-
`ployed as a second-line treatment. However, PSA re-
`sponse was observed in only 3 of 10 cases (30%). DXM
`
`173.72.4.37 - 1/4/2017 6:35:02 PM
`Downloaded by: B. Hare - 405798
`
`12
`
`Urol Int 2002;68:10–15
`
`Morioka/Kobayashi/Furukawa/Jo/Shinkai/
`Matsuki/Yamamoto/Tanaka
`
`
`
`173.72.4.37 - 1/4/2017 6:35:02 PM
`Downloaded by: B. Hare - 405798
`
`Table 2. Patient characteristics and PSA
`response after initiating DXM therapy
`(n = 27)
`
`Parameters
`
`Range (median)
`
`Average, 95% CI
`
`Age at initiation of DXM
`Bone scan positive
`EOD score at initiation of DXM
`CT scan positive (soft tissue)
`PSA at initiation of DXM, ng/ml
`PSA nadir during DXM, ng/ml
`Time-to-PSA nadir, weeks (n = 21)
`Maximum PSA decline, %
`! 25%
`25 &25 ! 50%
`50& ! 80%
`780%
`Time-to-PSA failure after DXM, months
`Survival period after DXM, months
`All (n = 27)
`PSA decline 7 50% (n = 16)
`PSA decline ! 50% (n = 11)
`Overall follow-up period, months
`
`60–91 (72)
`27
`1–4 (3)
`4
`5.5–639 (75.0)
`0.1–639 (28.8)
`2–76 (14)
`0–98.7 (56.6)
`10 (37.0%)
`1 (3.7%)
`5 (18.5%)
`11 (40.7%)
`1.0–21.5 (5.4)
`
`3.8–28.7 (13.1)
`8.1–28.7 (15.9)
`3.8–21.4 (7.7)
`13.6–94.7 (40.0)
`
`125.5, 74.5–176.5
`79.1, 29.1–129.1
`18.8, 7.5–45.1
`52.2, 37.1–67.3
`
`6.4, 4.6–8.3
`
`14.3, 11.4–17.2
`17.9, 14.4–21.4
`9.1, 5.9–12.3
`42.3, 35.6–49.0
`
`Table 3. Prognostic factors for significant
`PSA response (750% decline) and survival
`after initiating DXM therapy
`
`Parameters
`
`PSA decline
`750%
`
`univariate
`analysisa
`p value
`
`Survival period after DXM
`
`univariate
`analysisb
`p value
`
`multivariate analysisc
`hazards ratio
`p value
`
`Prior EBR, + vs. –
`Prior EMP, + vs. –
`Gleason sum, & 6 vs. 77
`Response duration to first-line
`therapy, ! 352 vs. 7352 days
`PSA at DXM start, ! 75 vs. 775 ng/ml
`PSA decline, ! 50% vs. 750%
`
`0.0535
`0.2388
`0.2321
`
`0.0540
`0.3095
`–
`
`0.0003
`0.9699
`0.0912
`
`0.0639
`0.7499
`!0.0001
`
`2.81, 0.5642
`2.13, 0.1007
`2.09, 0.4970
`
`1.80, 0.7155
`2.24, 0.4214
`2.70, 0.0055
`
`EBR = External beam radiotherapy, EMP = estramustine phosphate, DXM = dexametha-
`sone.
`a Univariate analysis: ¯2 test, PSA decline ! 50% vs. 750%.
`b Univariate analysis: log-rank test.
`c Multivariate analysis: Cox proportional hazards model.
`
`Main adverse effects of DXM therapy include weight
`gain and steroid face. However, only 2 patients were
`forced to discontinue DXM therapy despite significant
`PSA responses at 12 and 15 months, respectively. One
`patient was excused as a result of progressive congestive
`heart failure. The second case presented with exacerba-
`tion of diabetes mellitus.
`Background factors, which may affect PSA response
`and survival following DXM therapy, were analyzed by
`
`univariate and multivariate analyses. By univariate analy-
`sis, no meaningful factors for PSA decline of greater than
`50% were detected. Significant factors impacting survival
`period following DXM therapy were prior history of EBR
`(p = 0.003, log-rank) and PSA decline of greater than 50%
`(p ! 0.0001, log-rank). By multivariate analysis, PSA
`decline of greater than 50% was the sole meaningful prog-
`nostic factor for survival period (p = 0.0055, Cox propor-
`tional hazards model) (table 3).
`
`Dexamethasone Therapy in Patients with
`Hormone-Refractory Prostate Cancer
`
`Urol Int 2002;68:10–15
`
`13
`
`
`
`173.72.4.37 - 1/4/2017 6:35:02 PM
`Downloaded by: B. Hare - 405798
`
`Table 4. PSA response rate to glucocorticoid (GC) therapy in the literature
`
`Group (first author)
`
`Types of GC,
`doses (per day)
`
`PSA decline
`750%
`
`Harland, 1992 [10]
`Kelly, 1995 [7]
`Kantoff, 1999 [4]
`Tannock, 1996 [3]
`Sartor, 1998 [9]
`
`Hydrocortisone, 40 mg
`Hydrocortisone, 40 mg
`Hydrocortisone, 40 mg
`Prednisone, 10 mg
`Prednisone, 20 mg
`
`Storlie, 1995 [8]
`Nishiyama, 1998 [15]
`Small, 2000 [11]
`Present study
`
`Dexamethasone, 1.5 mg
`Dexamethasone, 1.5 mg
`Hydrocortisone, 40 mg
`Dexamethasone, 1.5 mg
`
`8/15 (53%)
`6/30 (20%)
`25/116 (22%)
`12/54 (22%)
`10/29 (34%)
`
`23/38 (61%)
`4/7 (57%)
`37/230 (16%)
`16/27 (59%)
`
`a PSA responder = PSA decline of at least 50%; b ND = not described.
`
`Response
`duration
`months
`
`Mean 6.0
`Median 4.0
`Median 2.3
`NDb
`Median 2.0,
`Mean 2.8
`Mean 8.1
`Range 3–11
`ND
`Median 5.4,
`Mean 6.4
`
`Median survival
`after GC, months
`all, PSA respondera
`
`ND
`ND
`12.6, 20.5
`50% at 10 months
`12.8, 17.4
`
`ND
`ND
`9.3, ND
`13.1, 15.9
`
`Discussion
`
`As second-line treatment for HRPC, antiandrogen
`(flutamide or bicalutamide) is indicated in patients who
`have failed to respond to first-line ADT. Otherwise EMP
`may be indicated for such patients. In cases in which CAB
`therapy has failed, AWS should be considered initially.
`Thereafter, second- or third-line hormonal therapies, such
`as adrenal blocking agents or glucocorticoids, should be
`considered. The efficacy of glucocorticoid therapy in
`HRPC patients involving hydrocortisone [4, 7, 10, 11],
`prednisone [3, 9] or DXM [8, 15] has been examined. In
`those reports, PSA response rate (decline of at least 50%)
`varied from 16 to 60%, and time-to-progression or time-
`to-PSA failure ranged from 2 to 8 months. Sartor et al. [9]
`noted that PSA response rate (decline of greater than
`50%) was elevated in patients treated with higher doses of
`glucocorticoids; that is, treatment with prednisone at
`20 mg/day versus prednisone at 10 mg/day, or hydrocorti-
`sone at 30 mg/day. PSA response rate was higher in
`patients treated with DXM (57–61%) than in those
`treated with prednisone or hydrocortisone (table 4). How-
`ever, all studies employing DXM, including the present
`study, are of a retrospective nature. On the other hand,
`PSA response rates in prospective trials involving hydro-
`cortisone or prednisone were 16–22% [3, 4, 11]. In the
`present study, PSA response was correlated to survival
`following DMX therapy. Significant differences were ob-
`served between patients displaying PSA decline of greater
`than 50% and those exhibiting PSA decline of less than
`
`50%. In contrast, no meaningful differences were ob-
`served for patients displaying PSA decline of greater than
`80% versus less than 80%. It is well known that PSA
`decline does not correlate with tumor regression or longer
`survival in all cases of HRPC. Given this inconsistency, it
`is appropriate to evaluate both PSA changes and pallia-
`tive effects in clinical trials involving HRPC patients [3,
`4, 11]. Evidence exists, however, which suggests that
`patients exhibiting a PSA decline of greater than 50%
`demonstrate longer survival than those displaying no sig-
`nificant PSA response. The present study is such an exam-
`ple [4, 9]. As a result, it is important to predict which
`patients are most likely to benefit from glucocorticoid
`therapy. Petrylak et al. [16] reported that prior history of
`chemotherapy and/or whole pelvis radiation affected PSA
`response in trials employing EMP plus docetaxel. Prior
`history of EBR and response duration to first-line hor-
`monal therapy may be important factors; however, they
`did not reach the significance as prognostic factors for
`PSA response in the present study. Patients with no prior
`EBR and longer response duration to first-line hormonal
`therapy may benefit from DXM therapy. However, due to
`the retrospective nature of the present study, it is inappro-
`priate to draw definite conclusions when attempting to
`predict PSA response.
`Glucocorticoid therapy for patients presenting with
`HRPC has been shifting from monotherapy to combina-
`tion therapy with mitoxantrone [3, 4]. This combination
`therapy has become the standard modality for symptom-
`atic HRPC patients; however, no significant effect on sur-
`
`14
`
`Urol Int 2002;68:10–15
`
`Morioka/Kobayashi/Furukawa/Jo/Shinkai/
`Matsuki/Yamamoto/Tanaka
`
`
`
`vival duration was observed when compared to glucocor-
`ticoid monotherapy. The efficacy of EMP plus docetaxel
`and mitoxantrone plus glucocorticoid is being studied
`where response duration and survival are utilized as end
`points [5]. Mitoxantrone has not yet been approved for
`
`clinical use for prostate cancer in Japan. As a result, DXM
`therapy remains one of the most beneficial treatment
`modalities in HRPC patients. The advantage of DXM is
`due to its considerable clinical effect as well as its low
`morbidity and economical cost.
`
`References
`
`1 Scher HI, Steineck G, Kelly WK: Hormone-
`refractory (D3) prostate cancer: Refining the
`concept. Urology 1995;46:142–148.
`2 Reese DM, Small EJ: Secondary hormonal ma-
`nipulations in hormone refractory prostate
`cancer. Urol Clin North Am 1999;26:311–
`321.
`3 Tannock IF, Osaba D, Stockler MR, Ernst DS,
`Neville AJ, Moore MJ, Armitage GR, Wilson
`JJ, Venner PM, Coppin CML, Murphy KC:
`Chemotherapy with mitoxantrone plus predni-
`sone or prednisone alone for symptomatic hor-
`mone-resistant prostate cancer: A Canadian
`randomized trial with palliative end points. J
`Clin Oncol 1996;14:1756–1764.
`4 Kantoff PW, Halabi S, Conaway M, Picus J,
`Kirshner J, Hars D, Trump D, Winer EP,
`Vogelzang NJ: Hydrocortisone with or without
`mitoxantrone in men with hormone-refractory
`prostate cancer: Results of the cancer and leu-
`kemia group B 9182 study. J Clin Oncol 1999;
`17:2506–2512.
`5 Hussain M, Petrylak D, Fisher E, Tangen C,
`Crawford D: Docetaxel (Taxotere) and estra-
`mustine versus mitoxantrone and prednisone
`for hormone-refractory prostate cancer: scien-
`tific basis and design of Southwest Oncology
`Group Study 9916. Semin Oncol 1999;
`26(suppl 17):55–60.
`
`6 Kreis W, Budman DR, Fetten J, Gonzales AL,
`Barile B, Vinciguerra V: Phase I trial of the
`combination of daily estramustine phosphate
`and intermittent docetaxel in patients with
`metastatic hormone refractory prostate cancer.
`Ann Oncol 1999;10:33–38.
`7 Kelly WK, Curley T, Leibretz C, Dnistrian A,
`Schwarz M, Scher HI: Prospective evaluation
`of hydrocortisone and suramin in patients with
`androgen-independent prostate cancer. J Clin
`Oncol 1995;13:2208–2213.
`8 Storlie JA, Buckner JC, Wiseman GA, Burch
`PA, Hartman LC, Richardson RL: Prostate-
`specific antigen levels and clinical response to
`low-dose dexamethasone for hormone-refrac-
`tory metastatic prostate carcinoma. Cancer
`1995;76:96–100.
`9 Sartor O, Weinberger M, Moore A, Li A, Figg
`WD: Effect of prednisone on prostate-specific
`antigen in patients with hormone-refractory
`prostate cancer. Urology 1998;52:252–256.
`10 Harland SJ, Duchesne GM: Suramin and pros-
`tate cancer: The role of hydrocortisone. Eur J
`Cancer 1992;28A:1295.
`
`11 Small EJ, Meyer M, Marshall ME, Reyno LM,
`Meyers FJ, Natale RB, Lenehan PF, Chen L,
`Slichenmyer WJ, Eisenberger M: Suramin ther-
`apy for patients with symptomatic hormone-
`refractory prostate cancer: Results of a ran-
`domised phase III trial comparing suramin
`plus hydrocortisone to placebo plus hydrocorti-
`sone. J Clin Oncol 2000;18:1440–1450.
`12 Hahn EA, Webster KA, Cella D, Fairclough
`DL: Missing data in quality of life research in
`Eastern Cooperative Oncology Group (ECOG)
`clinical trials: Problems and solutions. Stat
`Med 1998;17:547–559.
`13 Waselenko JK, Dawson NA: Management of
`progressive metastatic prostate cancer. Oncolo-
`gy 1997;11:1551–1560.
`14 Oh WK, Kantoff PW: Management of hor-
`mone refractory prostate cancer: Current stan-
`dards and future prospects. J Urol 1998;160:
`1220–1229.
`15 Nishiyama T, Terunuma M: Hormone/anti-
`hormone withdrawal and dexamethasone for
`hormone-refractory prostate cancer. Int J Urol
`1998;5:44–47.
`16 Petrylak DP, Macarthur RB, O’Connor J, Shel-
`ton G, Judge T, Balog J, Pfaff C, Bagiella E,
`Heitjan D, Fine R, Zuech N, Sawezuk I, Ben-
`son M, Olsson CA: Phase I trial of docetaxel
`with estramustine in androgen-independent
`prostate cancer. J Clin Oncol 1999;17:958–
`967.
`
`173.72.4.37 - 1/4/2017 6:35:02 PM
`
`Dexamethasone Therapy in Patients with
`Hormone-Refractory Prostate Cancer
`
`Urol Int 2002;68:10–15
`
`15