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`
`original article
`
`Annals of Oncology 21: 319–324, 2010
`doi:10.1093/annonc/mdp323
`Published online 24 July 2009
`
`Sunitinib malate for metastatic castration-resistant
`prostate cancer following docetaxel-based
`chemotherapy
`G. Sonpavde1,2*, P. O. Periman1,3, D. Bernold1,4, D. Weckstein1,5, M. T. Fleming1,6,
`M. D. Galsky1,7, W. R. Berry1,8, F. Zhan1, K. A. Boehm1, L. Asmar1 & T. E. Hutson1,9
`1US Oncology Research, Inc., Houston, TX; 2Texas Oncology PA, Webster, TX; 3Texas Oncology PA, Amarillo, TX; 4Interlakes Oncology Hematology, Rochester, NY;
`5New Hampshire Hematology-Oncology, P.A., Hooksett, NH; 6Virginia Oncology Associates, Hampton, VA; 7Comprehensive Cancer Centers of Nevada, Las Vegas,
`NV; 8Cancer Centers of North Carolina, Raleigh, NC and 9Baylor Sammons Cancer Center, Dallas, TX, USA
`
`Received 22 January 2009; revised 7 April 2009; accepted 12 May 2009
`
`Background: Systemic therapy options are limited for metastatic castration-resistant prostate cancer (CRPC)
`patients who progress following docetaxel (Taxotere). This phase II trial evaluated sunitinib malate in patients with
`progressing metastatic CRPC following prior docetaxel.
`Patients and methods: Patients with metastatic CRPC progressing following one to two chemotherapy regimens
`including docetaxel were included. The primary end point was progression-free survival (PFS) per radiographic and
`clinical evaluations. Oral sunitinib was administered 50 mg/day 4-weeks on followed by 2-weeks off per cycle up to
`a maximum of eight cycles or until clinical progression or intolerable toxicity.
`Results: Thirty-six patients with a median age of 69.5 years were accrued. The median PFS was 19.4 weeks with
`a 12-week PFS of 75.8%. Four patients (12.1%) had a ‡50% prostate-specific antigen (PSA) decline and seven
`(21.2%) had a ‡30% PSA decline. Two of 18 patients (11.1%) with measurable disease demonstrated 30% declines
`by RECIST and eight (44.4%) displayed some shrinkage. A decline in pain score ‡2 points occurred in 13.6% of 22
`assessable patients. Drug discontinuation due to toxic effects occurred in 52.8% of patients.
`Conclusion: Sunitinib malate demonstrated promising activity in metastatic CRPC progressing after prior docetaxel.
`Key words: castration-resistant prostate cancer, sunitinib malate
`
`introduction
`
`Docetaxel-based chemotherapy has a palliative role in patients
`with metastatic castration-resistant prostate cancer (CRPC)
`with a median overall survival (OS) of 19 months and a median
`progression-free survival (PFS) of 6 months [1–3]. Following
`docetaxel, effective salvage options are lacking [4, 5]. Sunitinib
`malate is an orally administered multitargeted tyrosine kinase
`inhibitor (TKI) that is approved for metastatic renal cell cancer
`and gastrointestinal stromal tumors and displays selectivity for
`platelet-derived growth factor (PDGF) receptors, vascular
`endothelial growth factor (VEGF) receptors, Flt3, and Kit
`[6–8]. Given the preclinical evidence for the role of VEGF and
`PDGF receptor signaling in promoting prostate cancer growth,
`a rationale can be made to evaluate sunitinib for patients with
`progressive metastatic CRPC following docetaxel [9–12].
`Advanced prostate cancer is characterized by a poor ability to
`measure response due to immeasurable bone-only metastases or
`prostate-specific antigen (PSA)-only disease. Although a ‡30%
`
`*Correspondence to: Dr G. Sonpavde, Texas Oncology Cancer Center, 501 Medical
`Center Boulevard, Webster, TX 77598, USA. Tel: +1-281-332-7505;
`Fax: +1-281-332-8429; E-mail: Guru.Sonpavde@USOncology.com
`
`PSA decline in 3 months may be a useful surrogate for outcomes
`with chemotherapeutic agents, its validity with biological agents
`is unknown [13–15]. In addition, discordant PSA and clinical
`responses have been observed with sorafenib [16]. Other useful
`intermediate surrogates such as circulating tumor cells require
`further validation [17]. Time-to-event end points may be
`clinically useful surrogates and are currently recommended by
`the Prostate Cancer Working Group-2 guidelines [15]. In
`particular, PFS defined as a composite end point constituted by
`symptomatic or radiological progression may be a relevant end
`point that dictates clinical decision making and appears to be
`a useful intermediate surrogate for survival [18].
`
`patients and methods
`
`patients
`Key inclusion criteria included histologically confirmed adenocarcinoma of
`the prostate with radiographic metastatic disease who had received one to
`two prior chemotherapy regimens including docetaxel (Taxotere; Sanofi-
`Aventis, Bridgewater, New Jersey). Progressive disease by PSA or clinical
`criteria was required. PSA progression was defined as a baseline increase
`followed by any serial increase after 2 weeks, with the last confirmatory PSA
`
`ª The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
`All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
`
`AVENTIS EXHIBIT 2107
`Mylan v. Aventis, IPR2016-00712
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`original article
`
`being ‡10 ng/ml. The Eastern Cooperative Oncology Group (ECOG)
`performance status was required to be zero to two. Androgen ablation
`therapy (luteinizing hormone-releasing hormone agonist or orchiectomy)
`with testosterone level <50 ng/dl was required. Adequate cardiac function
`by investigator judgment was required with no uncontrolled arrhythmia or
`hypertension, with radiological cardiac evaluation as per investigator
`discretion. Adequate renal, hepatic, and hematological function was also
`required. Patients who had received prior radionuclides or radiation to
`>50% of the bone marrow were excluded. Significant bleeding in the
`previous 4 weeks and significant acute cardiovascular morbidities in the
`previous 6 months were exclusion criteria. Additionally, previous radiation
`therapy, surgery and systemic therapy were required to be completed >4
`weeks before therapy.
`
`study design
`This was an open label, phase II trial conducted at 10 community cancer
`centers in the US Oncology Network. Patients were treated with sunitinib
`until progressive disease or intolerable toxicity and for a maximum of eight
`6-week cycles. The composite PFS primary end point was similar to the
`definition of progression employed in the large phase III Satraplatin and
`Prednisone against Refractory Cancer salvage trial [5]. PSA increases were
`not used to determine progression. Progression was defined as the first
`occurrence of any of the following: two distinct new lesions on bone scan,
`progression of measurable disease by RECIST criteria, worsening of pain by
`‡2 points on the six-point present pain intensity (PPI) scale, urinary tract
`obstruction, bone-related events (pathological fracture, spinal cord
`compression, need for palliative radiation, surgery or kyphoplasty to any
`neoplastic bone lesion) or a deterioration of performance status to an
`ECOG score of three or four [19, 20]. The secondary end points were PSA
`declines (‡30% and ‡50%), PSA-doubling time (DT), measurable disease
`response rate by RECIST, quality of life (QoL) by Functional Assessment of
`Cancer Therapy-prostate (FACT-P), PPI, safety and survival [19–22]. The
`protocol was approved by a central Institutional Review Board.
`
`administration of study therapy
`Patients received sunitinib 50 mg/day orally on days 1–28 of each 6-week
`cycle for up to a maximum of eight cycles or until progression,
`unacceptable toxicity or withdrawal of consent. Up to two dose reductions
`were allowed with the dose adjusted to 37.5 mg/day and then to 25 mg/day
`in the event of toxic effects. For grade 3 or 4 toxic effects, the treatment was
`withheld until the patient recovered completely or to grade 1 toxicity,
`followed by resumption at a first level dose reduction. Patients who were off
`therapy for >3 weeks were removed from therapy.
`
`assessments
`Safety assessments were carried out every cycle (6 weeks) or earlier if
`clinically indicated and up to 30 days following the last dose of sunitinib.
`The severity of toxic effects was graded using the National Cancer
`Institute—Clinical Trial Criteria for Adverse Events version 3 [22]. The
`PSA-DT was assessed at baseline and on therapy. The PPI was self-assessed
`daily during treatment. After baseline radiological work-up, subsequent
`radiological evaluations were carried out every two cycles (12 weeks) or
`earlier if clinically indicated. Cardiac function evaluation was carried out
`according to the investigator discretion. Laboratory evaluations (complete
`blood cell counts and comprehensive metabolic panel), PSA, and FACT-P
`QoL assessments were repeated every 6 weeks. Generalized trends in use of
`pain medication were calculated based on reports by the patient as stable,
`increased, or decreased in each cycle compared with the prior 6-week cycle.
`
`statistical methods
`The median PFS with similar end points with other agents in the second-
`line setting after docetaxel has been 2.5 months [4, 5]. Given the
`
`Annals of Oncology
`
`convenience of oral administration of sunitinib, modest activity was
`considered clinically meaningful in this relatively heavily pretreated
`population that had received one to two prior chemotherapy regimens. The
`null hypothesis for this trial was that the 12-week PFS was <15% (not
`clinically meaningful) with the alternative hypothesis being that the true
`PFS was 30%. Thirty-four patients were deemed to be required according to
`the STPlan (M.D. Anderson Cancer Center) with a level of 5% and 80%
`power. Kaplan–Meier techniques in SASÒ were employed on the intention-
`to-treat population to assess time-to-event analyses such as PFS and OS
`[23]. If no major toxic effects (six or more patients with grade 4
`hematological and/or grade 3 or higher non-hematological toxic effects)
`related to sunitinib occurred among the first 20 patients during cycle 1, the
`study would keep accruing. The PSA-DT was calculated by linear
`regression.
`
`results
`
`patient characteristics
`
`Thirty-six patients with metastatic CRPC were enrolled in the
`trial (Table 1). The median age was 69.5 years and the median
`PSA was 215 ng/ml. All patients had received prior docetaxel
`chemotherapy, four patients (11.1%) had received prior
`
`Table 1. Patient characteristics at baseline
`
`Characteristic
`
`Age (years)
`Median
`Range
`Race, n (%)
`White
`Black
`Hispanic
`ECOG performance status, n (%)
`0
`1
`2
`Prior therapy, n (%)
`Chemotherapya
`Docetaxel
`Mitoxantrone
`Otherb
`Bevacizumab
`Radiotherapyc
`Surgery
`Prostatectomy
`Site of metastasis, n (%)
`Bone
`Soft tissue/lymph node
`Visceral
`PSA, n (%)
`Median
`Range
`
`N = 36
`
`69.5
`52.6–86.5
`
`32 (88.9)
`3 (8.3)
`1 (2.8)
`
`12 (33.3)
`21 (58.3)
`3 (8.3)
`
`36 (100)
`36 (100)
`2 (5.6)
`11 (30.6)
`4 (11.1)
`21 (58.3)
`26 (72.2)
`17 (65.4)
`
`32 (88.9)
`8 (22.2)
`6 (16.7)
`
`215
`4.1–4033.0
`
`aSubjects may have had one to two prior agents.
`bOther included carboplatin (n = 3), cyclophosphamide (n = 3), paclitaxel
`(n = 3), estramustine (n = 1), and gemcitabine (n = 1).
`cSites of radiation included bone (n = 16), prostate (n = 9), pelvic (n = 4),
`and breast (n = 1).
`ECOG, Eastern Cooperative Oncology Group; PSA, prostate-specific
`antigen.
`
`320 | Sonpavde et al.
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`Annals of Oncology
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`bevacizumab, two (5.6%) had received mitoxantrone, and 11
`(30.6%) had received other agents (Table 1). The most
`common site of metastatic disease was bone (88.9%).
`
`activity of sunitinib
`
`The median PFS was 19.4 weeks with a PFS at 12 weeks of
`75.8%, and a PFS of 6.2% at 48 weeks. The median survival
`was 43.7 weeks (range 2.6–72.7 weeks). Four patients (12.1%)
`had a ‡50% PSA decline and seven (21.2%) had a ‡30% PSA
`decline compared with baseline (Figure 1A). Of the four
`patients previously treated with bevacizumab, one patient
`displayed a ‡50% PSA decline and another displayed a ‡30%
`PSA decline. When examining ‡30% PSA declines stratified by
`best response to prior chemotherapy, 5 of 18 patients with
`prior response or stable disease (employing conventional
`clinical, PSA and RECIST) responded and 1 of 14 with prior
`progressive disease responded, and these data were not
`statistically different. Overall, 10 patients (30.3%) exhibited
`some decline of PSA compared with baseline, while 15
`patients (45.5%) exhibited some decline of PSA compared
`with the previous PSA value (Table 2). The median PSA-DT
`was prolonged on therapy (3.1 months) compared with
`pretherapy (1.4 months). Two of 18 patients (11.1%) with
`measurable disease at baseline demonstrated unconfirmed
`‡30% declines in size by RECIST and eight patients (44.4%)
`displayed some reduction in size compared with baseline
`(Figure 1B). Of the two patients with 30% RECIST declines in
`size, one patient experienced a ‡50% PSA decline and pain
`score decline ‡2 points, while the other patient had a <30%
`PSA decline. Declines in size could not be confirmed with
`another scan probably due to frequent discontinuation of
`therapy for toxic effects. Overall, a decline in pain score of ‡2
`points was noted in three patients (13.6%), while a decline ‡1
`point was noted in 11.0 (50%) of 22 assessable patients. Five
`of the 11 patients with declines in pain scores demonstrated
`discordant PSA increases. Analgesic intake decreased in six
`patients (17.1%) and was stable in 10 patients (28.6%). The
`
`original article
`
`median number of cycles completed was 2 (range 1–7); 14
`patients completed one cycle of therapy, nine completed two
`cycles, and six completed three cycles. The primary cause of
`drug discontinuation was toxic effects (52.8%) followed by
`progressive disease (33.3%). Dose reduction to 37.5 and
`25 mg daily was required in seven and three patients (8.7%),
`respectively. It appears that many patients preferred to
`discontinue therapy than continue with a dose reduction.
`The high proportion of drug discontinuation led to
`a median time-to-treatment failure (TTF) of 11.8 weeks
`(range 2.0–38.6 weeks).
`
`safety
`
`Fatigue, anemia, nausea, anorexia and neutropenia were
`the most common toxic effects (Table 3). Severe grade 3–4
`toxic effects were infrequent with fatigue (n = 6), anorexia
`(n = 5), nausea (n = 3), and diarrhea and leukopenia (n = 2
`each), being the most common. Two deaths were deemed
`to be possibly related to study therapy including one
`non-neutropenic infection and one cerebrovascular
`hemorrhage, although a definitive causative link could not
`be established.
`
`quality of life
`
`There were trends toward improvement in the prostate cancer
`subscale of the QoL (P = 0.06) and a general trend toward
`improvement. However, the small sample size and small
`proportion of patients returning questionnaires at the end of
`treatment (n = 9) were too limited to make definitive
`conclusions. Additionally, the high rate of drug discontinuation
`likely compromised the quality of these data.
`
`discussion
`
`This phase II trial evaluated the safety and activity of single-
`agent sunitinib (without concurrent corticosteroids) in patients
`
` PSA and RECIST waterfall charts
`(A) PSA *
`
`100
`
`-40
`50
`Maximum Change from Baseline (%)
`
`40
`
`20
`
`0
`
`-20
`
`0
`
`-50
`
`* Any increase (%) > 100 truncated to 100
`
`30% Decrease
`50% Decrease
`
`(B) Sum of lesions by RECIST criteria *
`
`* Four patients without post-baseline tumor assessment were excluded.
`
`30% Decrease (not confirmed)
`
`-60
`
`-80
`
`Figure 1. (A and B) Prostate-specific antigen (PSA) and RECIST waterfall charts.
`
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`Table 2. Efficacy of sunitinib
`
`Characteristic
`Clinical PFS (N = 36)
`Median (weeks)
`Range
`12-week PFS
`Overall survival (N = 36)
`Median (weeks)
`Range
`6-month (26 week) survival
`PSA response (N = 33), n (%)
`30% decline compared
`with baselinea
`50% decline compared
`with baseline
`Any PSA decline
`Compared with baseline
`During treatment compared
`with previous PSA
`PSA-DT (months) (N = 28), median (range)
`At baseline (n = 28)
`At end of treatment
`(n = 28)
`Difference between baseline
`and EOT (n = 25)
`Objective responses (RECIST) (N = 18b), n (%)
`CR
`PR
`Some shrinkage compared
`with baseline
`PPI (N = 22c), n (%)
`At least one decrease
`<2 points
`At least one decrease
`‡2 points
`Use of pain medications (N = 35), n (%)
`Decreased
`Increased
`Remained the same
`Data incomplete
`
`Reason for discontinuation, n (%)
`Progressive disease/recurrence
`Toxicityd
`Patient requeste
`Found to be ineligible/removed
`
`Total cycles received
`
`Range
`
`Survival, n (%)
`Alive
`Dead
`
`Cause of death, n (%)
`Disease progression
`Pulmonary embolismf
`Atrial fibrillationf
`Sepsisg
`Strokeh
`
`19.4
`2.6 to 48.3
`75.8%
`
`43.7
`2.6 to 72.7
`73.1%
`
`7 (21.2)
`
`4 (12.1)
`
`10 (30.3)
`15 (45.5)
`
`1.4 (0.3 to 24.4)
`3.1 (0.4 to 54.6)
`
`0.5 (25.1 to 43.7)
`
`0
`2 (11.1)
`8 (44.4)
`
`11 (50.0)
`
`3 (13.6)
`
`6 (17.1)
`7 (20.0)
`10 (28.6)
`12 (34.3)
`
`12 (33.3)
`19 (52.8)
`4 (11.1)
`1 (2.8)
`
`2.0
`1 to 7
`
`18 (50.0)
`18 (50.0)
`
`12 (66.6)
`1 (5.6)
`1 (5.6)
`1 (5.6)
`1 (5.6)
`
`Table 2. (Continued)
`
`Characteristic
`
`Unknown, no autopsy
`carried out
`
`Annals of Oncology
`
`2 (11.1)
`
`aIncludes three patients with 50% decrease; of the four patients previously
`treated with bevacizumab, one had a >50% PSA decline and one had a 30%
`PSA decline.
`bOnly patients with baseline measurable lesions included in this analysis
`and responses were unconfirmed by repeat scanning.
`c35 patients completed PPI diaries; 22 patients had pain (1–6) at baseline:
`decreases and increases are measured from baseline.
`dn = 1 each: n/v; pain; pulmonary embolism; sepsis (death); atrial
`fibrillation (death); taste disturbance and anorexia; bone pain and n/v;
`pancreatitis; stroke (death); muscle weakness; anorexia and n/v; myalgia
`and decreased ECOG PS; cellulitis; sepsis, renal failure, and anemia;
`neutropenia; and drug reaction.
`en = 1, PSA was rising and patient wanted to stop therapy; n = 4 withdrew
`consent and entered hospice.
`fDeemed unrelated to treatment and occurred off therapy.
`gNon-neutropenic, possibly related to treatment.
`hPossibly related to treatment.
`PFS, progression-free survival; PSA, prostate-specific antigen; DT, doubling
`time; EOT, end of therapy; n/v, nausea/vomiting.
`
`with relatively heavily pretreated patients with metastatic CRPC
`that had progressed following docetaxel. Additionally, 36.2% of
`patients had received one other chemotherapeutic agent and
`11.1% had also received prior bevacizumab. With the caveat
`that this is a modest sized phase II trial, the relatively high
`composite 12-week PFS of 75.8% accompanied by ‡50% and
`‡30% PSA declines in 12.1% and 21.2% of patients,
`respectively, support sunitinib being an active agent in this
`disease. Although PFS is a soft end point in the setting of
`metastatic CRPC, it is a relevant end point that dictates clinical
`decisions. While PSA declines were seen without confirmed
`PSA responses, these levels of PSA declines appear to be
`intermediate surrogates for long-term outcomes with
`chemotherapy [13, 14]. Additionally, of 18 assessable patients,
`two (11.1%) exhibited an unconfirmed ‡30% tumor shrinkage
`by RECIST and eight (44.4%) exhibited some reduction in
`tumor size. In addition, two of the four patients who had
`received prior bevacizumab displayed a ‡50% PSA decline and
`a ‡30% PSA decline, suggesting that these agents may not be
`completely cross-resistant. The phenomenon of PSA elevations
`coupled with clinical benefit (pain response) observed in other
`trials with similar TKIs was also noted [16]. Sunitinib
`administered on a similar schedule has displayed evidence of
`activity against metastatic CRPC in another phase II trial
`conducted in the first- and second-line settings with a primary
`biochemical end point [24]. Sunitinib also appears feasible in
`combination with docetaxel in the frontline setting for CRPC
`and when combined with androgen deprivation as neoadjuvant
`therapy for localized prostate cancer. Additionally, other
`multitargeted TKIs (sorafenib, AZD2171) have exhibited
`activity in the setting of CRPC [16, 25–27].
`
`322 | Sonpavde et al.
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`Annals of Oncology
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`Table 3. Toxic effects in more than one patient
`
`original article
`
`Adverse event
`
`Grade 1
`
`Grade 2
`
`Grade 3
`
`Grade 4
`
`Grade 5
`
`Total (%)
`
`Hematological
`Anemia
`Leukopenia
`Neutropenia
`Thrombocytopenia
`Non-hematological
`Alkaline phosphatase increase
`Anorexia
`Cerebrovascular hemorrhage
`Constipation
`Diarrhea
`Edema
`Fatigue
`Hand–foot syndrome
`Hypertension
`Malaise
`Mucositis
`Muscle weakness
`Myalgia
`Nausea
`Peripheral neuropathy
`Rash
`Sepsis
`Stomatitis
`Taste alterations
`Vomiting
`Weight loss
`
`5
`1
`2
`2
`
`2
`6
`
`2
`7
`2
`4
`3
`0
`1
`7
`1
`1
`4
`1
`5
`
`1
`1
`1
`3
`
`7
`2
`8
`1
`
`0
`2
`
`0
`4
`0
`6
`0
`3
`0
`0
`0
`0
`5
`1
`0
`
`0
`2
`4
`1
`
`1
`2
`1
`1
`
`0
`5
`
`0
`2
`0
`6
`0
`0
`1
`0
`1
`1
`2
`0
`0
`
`1
`0
`0
`0
`
`0
`0
`0
`0
`
`0
`0
`
`0
`0
`0
`0
`0
`0
`0
`0
`0
`0
`1
`0
`0
`
`0
`0
`0
`0
`
`13 (37.1)
`5 (14.3)
`11 (31.4)
`4 (11.4)
`
`2 (5.7)
`13 (37.1)
`1 (2.8)
`2 (5.7)
`13 (37.1)
`2 (5.7)
`16 (45.7)
`3 (8.6)
`3 (8.6)
`2 (5.7)
`7 (20.0)
`2 (5.7)
`2 (5.7)
`12 (34.3)
`2 (5.7)
`5 (14.3)
`1 (2.8)
`2 (5.7)
`3 (8.6)
`5 (14.3)
`4 (11.4)
`
`1a
`
`1a
`
`aCerebrovascular hemorrhage (n = 1) and non-neutropenic sepsis (n = 1) led to death in two patients; both of these were deemed possibly due to study
`therapy.
`
`Although most toxic effects were mild, the majority of
`patients (52.8%) discontinued therapy due to toxic effects. As
`a result, the median TTF was a more modest 11.8 weeks
`compared to the median PFS of 19.4 weeks. This elderly
`population of relatively heavily pretreated patients with
`metastatic CRPC may tolerate even mild toxic effects poorly
`compared with younger patients treated in other settings [7, 8].
`Closer clinical monitoring and prompt dose reductions for
`early toxic effects may have mitigated these events. Therefore,
`the further development of sunitinib in this population
`warrants careful monitoring for toxic effects and optimal
`patient selection. Clinical cardiac dysfunction was not
`observed. However, routine cardiac function monitoring was
`not carried out due to the low incidence of clinical cardiac
`dysfunction and the lack of clear relevance of subclinical
`cardiac dysfunction in a population with advanced malignancy
`and limited survival.
`In conclusion, sunitinib malate displayed activity in the
`setting of metastatic CRPC following prior docetaxel. Given the
`high rate of discontinuation of therapy due to toxic effects, a
`lower dose and less heavily pretreated population may be more
`optimal. Indeed, an ongoing phase III trial in the second-line
`setting is comparing sunitinib 37.5 mg daily continuously plus
`prednisone versus placebo plus prednisone.
`
`funding
`
`Pfizer, Inc.
`
`acknowledgements
`
`We thank the patients who shared their experiences with US
`Oncology physicians (see Appendix), the site coordinators in
`the field (especially Tamberla S. Burks), Project Manager Alicia
`Williams, and data reviewers Cindy Brissman and Denise
`Elmore-Lockheed who assured the accuracy and integrity of the
`data. Previously presented at the 2008 American Society of
`Clinical Oncology Annual Meeting, Chicago, IL.
`
`appendix
`
`The following oncologists from US Oncology Network
`institutions also participated in this study: Rony Abou Jawde,
`St Joseph, MO; Thomas Boyd, Yakima, WA; Marcus P.
`Braun, Vancouver, WA; Ernest W. Cochran Jr, Paris, TX;
`Linda DeMarco, Hudson, NY; Asad Dean, Fort Worth, TX;
`Tony Ha, Yakima, WA; Stephen M. Hillinger, Albany, NY;
`Eileen M. Johnston, Edmonds, WA; Edwin C. Kingsley, Las
`Vegas, NV; Regan M. Look, Portland, OR; Jon K. Minford,
`Columbia, MD; Ashutosh Rashtogi, Midland, TX; Robert M.
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`doi:10.1093/annonc/mdp323 | 323
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`original article
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`Rotche, Christiansburg, PA; James D. Sanchez, Las Vegas,
`NV; Spencer H. Shao, Portland, OR; Richard S. Siegel,
`Arlington Hights, IL; Scott A. Stone, Plano, TX; Ceasar K.
`Tin-U, Sugar Land, TX; Robert Weigand, St. Joseph, MO;
`Ralph E. Weinstein, Portland, OR; and Charles S. White III,
`Dallas, TX.
`
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`324 | Sonpavde et al.
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`Volume 21 | No. 2 | February 2010