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`[EUROPEAN JOURNAL OF CANCER
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`Eur0pean Journal of Cancer
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`

`

`Vfilllllli‘4?
`
`Z’ 0'1 l
`
`European Journal of Cancer
`
`Contents
`
`Editorial comment
`
`Phase 1 trials of molecular targeted therapies: Are we evaluating toxicities properly?
`l-C.Sonn
`
`Short communication
`
`Motor vehicle exposure and risk of oesophageal adenocarcinoma
`
`l. Logergren, C. lansson and Y. Lu
`
`Reviews
`
`The preclinical and clinical activity of aviscumine: A potential anticancer drug
`H. Zwierzino, L. Bergmonn. H. Fiebig, S. Aomdal, P. Schdfislei. K. Witthohn and H. Lentzen
`
`Critical review of economic evaluations in multiple myeloma: An overview of the economic evidence and quality of the
`methodology
`J.G. Goultney, WK. Redekop, P. Sonneveld and CA. Uyl—de Groot
`
`Clinical oncology
`
`Heterogeneity in the definition of dose-limiting toxicity in phase 1 cancer clinical trials of molecularly targeted agents: A
`review of the literature
`
`C. Le Tournenu, nan. Rotate, H.l(. Can. 5. Pop, V. Die’ros, P. Trescn and X. Pooletti
`
`Extended schedule, escalated dose temozolomide versus dacarbazine in stage N melanoma: Final results of a randomised
`phase III study (EORTC 18032)
`PM. Patel, S. Suciu. L. Mortier, WH. Kruit, C. Robert. D. Sthadendorf, U. hefzer, CM. Punt, R. Dummer, N. Davidson, l. Becker,
`R. Corny, M. Thompson, er. Hum, K. Engelen, 8.3. Agorumlo, U. Keilholz, AMM. Eggermont and A. Spotz. on behalf ofthe EORTC
`Melanoma Group
`
`A phase I study of sirolimus and bevacizumab in patients with advanced malignancies
`HEW. Cohen, MR. Shanna, L. Jonisch, M. Llohreru, L. House, K. Wu, J. Ramirez, (1F. Fleming. WM. Stadler and MJ. Retain
`
`Reasons given by patients for participating, or not, in Phase 1 cancer trials
`S. Catt, C. Lnngridge, L. Followfield, DC. Talbot and V. Jenkins
`
`A randomised phase II trial of 1 month versus 1 year of adjuvant high—dose interferon v-Qb in high-risk acral melanoma
`patients
`L. Moo, L. Si. 2. Chi, C. Cui, X. Sheng, S. Li, B. Tang and l. Goa
`
`Adherence to national guidelines for treatment and outcome of endometrial cancer stage I in relation to co-morhidity in
`southern Netherlands 1995-2008
`
`D. Boll, ill-M. 1v’erhoeven, MA. van der no, MLM. Lybeert, MMW. Coebergh and MLG. Janssen-Heiinen
`
`An open-label, multicentre biomarker‘oriented A10 phase II trial of sunitinib for patients with chemo-refractory advanced
`gastric cancer
`M. Mochler. A. Mueller, J.T_ Hartmonn, MP. Ebert, S.E. ell-Button, P. Reimer, M. Weihrauch, F. Lordiclt, T. Trarhnch, S. Biesterleld,
`M. Kohlsch. D. Wachtlin and RR. Calls,
`the German Arbcitsgemeinschajt lnternistische Ontologie (AID)
`
`I’tinled by Poleslm Wlieatons Ltd, Exeter, UK
`
`1443
`
`1446
`
`1450
`
`1458
`
`1468
`
`14%
`
`1484
`
`1490
`
`1498
`
`150-1
`
`1511
`
`

`

`One-month relative dose intensity of not less than 50% predicts favourable progression-free survival in sortifenib therapy
`for advanced renal cell carcinoma in Japanese patients
`A. Kawashima, H. Tahayama, Y. Arai, G. Tanigataa, M. Nin, J. Kajlkawa, T. tmaza, T. Kinoshita, Y. Yasunaga, H. lnaue, it. Nishirnara,
`S. Taleada, K. Nishimnra, A. Tsujimura and N. Nonornara, The Osaka Renal Cell Carcinoma Clinical Study Collaboration
`
`Primary breast cancer patients with high risk clinicopathologic features have high percentages of bone marrow epithelial
`cells with ALDH activity and CDAJ’l‘CDQ‘l'0 cancer stem cell phenotype
`JM. Reuben, B.-N. Lee, H. Goa, EN. Cohen, M. Mean, A. Giordano, X. War-lg, A. Ladhi, S. Krishnamurthy, (LN. Hortabagyi,
`M. Cristofanilli, A. Lucci and WA. Woodward
`
`Peritumoural vascular invasion: A major determinant of niple-negative breast cancer outcome
`R. Sabatier, l. Jacquemier, F. Bertucci, B. Esterni, P. Finetti, F. Azan'a, D. Bimbaum, P.
`laliens, A. Goncalues and J.-M. Extra
`
`Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: A double blind randomised clinical
`phase III trial (CYCLUS study) by the Swedish Lung Cancer Study Group
`A. Koch, B. Bergman, E. Holmberg, C. Sederhoirn, L. Eh, J. Kasieradzhi, K. Lamberg, L. Thaning, S.-O. Ydreborg and S. Sb‘renson,
`On behalf of the Swedish Lung Cancer Study Group
`
`Paediatric oncology
`
`Phannacokinetics of cyclophosphamide and its metabolites in paediatric patients receiving high~dose myeloablative
`therapy
`G. Chinnaswamy, J. Errington, A. Foot, AV. Boddy, GJ. Veal and M. Cole
`
`Epidemiology and cancer prevention
`
`Couples' communication before the wife's death to cancer and the widower's feelings of guilt or regret after the loss — A
`population—based investigation
`JIM. )onasson, A. Haalasda'ttir, S. Nemes, PJ. Surlean, U. Vaidimarsdottir, E. Onelfiu and G. Steineck
`
`Adding familial risk assessment to faecal occult blood test can increase the effectiveness of population-based colorectal
`cancer screening
`N. Beaker, LCM. uan Rassurn, M. Van Wat-van Pinxteren, S.H.C. van Stiphout, R.P.M.G. Hermens, WAG. van Zelst-Stams,
`M.G.H. van Oijen, RN. taheij, 1.3M}. Jansen and N. Hoagerbrugge
`
`Experimental oncology/Translational research
`
`Efficacy of a leptin receptor antagonist peptide in a mouse model of triple'negative breast cancer
`L. Otaos in, I. Koaalszky, M. Riolfl. R.
`l-‘erla, _l. Utah, A. Satodola, K. Narna, A. Malina, Q. Piabello, JD. Wade and E. Surmacz
`
`pEZJSQSThtl involved in cisplatin resistance in human ovarian cancer cells by clearing obiquitinated proteins
`H. Ya, I. Su. Y. Xu. J. Kang, H. Li, L. Zhang, H. Yr, X Xionq, l' liu and L. Sun
`
`VEGF—SFECT with ”'In‘bevacizainab in stage lllll'v' n'rclanorna patients
`WE. Nagengast, MN. Lubsde Hinge, if M E van Stories, .5. Krinjfl, All. firouwers, WJ-‘A. den DunnenJll. delanq, l-l. Hollemo,
`RA. Dierclex, N.H. Mulder, ELLE de lines, ll]. lloehstra and (LAP. l-lospers
`
`l521
`
`152?
`
`1.53?
`
`1546
`
`1556
`
`1564
`
`1571
`
`1578
`
`1585
`
`1595
`
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`EltilER
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`lnclexerlr'Abstractod in:
`Current Contains;
`EMEAStIr’ENt'L-rpta Mean-a,-
`mat-x Metl'icus; MLIJLINE,‘
`CABS.BIDSlSDalnhose;
`Pascamnas Database, cer-a.‘
`
`,
`_
`“‘5” ”"189'8049
`
`

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`ELSEVIER
`
`available at www.3ciencedirectcom
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`-"
`”7? ScienceDirect
`
`journal homepage: WWWABlBOMi'm-com
`
`
`
`# R
`
`easons given by patients for participating, or not,
`in Phase 1 cancer trials
`
`s. cm c. Langridge a, L. Fallowfield 0, D.C. Talbot 1’, v. Jenkins “
`
`“ CR-UK Psychosocial Oncology Group, Brighton and Sussex Medical School. UK
`1‘ Department of MPdical Oncology. Clitirrhill Hospital, University of Oxford, Oxford. UK
`
`ARTICLEINFD
`
`ABSTRACT
`
`
`Article history
`Received Nanuary 2011
`Received in revised form 23l‘eht1tary
`2011
`Accepted :25 February 2011
`Available online 30 Match 2011
`
`
`Kevtuords:
`Cancer
`Phase ‘I trials
`Motivation
`
`Rigaggnb‘
`Conn-nunication
`'l‘rial participation
`
`lluclt't'jl'ritlnd.‘ Coitiintinicatitin with patients contemplating Phase 1 cancer trial participation
`can be challenging. Controversy exists as to whether they are provided with sufficient
`inforini-ttion to give genuinely informed consent. We ptesent data examining the reasons
`patients gave for trial entry.
`Method: Following discussions with oncologists about Phase'l trials. participants completed
`a 19-itein study specific 'accept or decline tnensnre' exploring hope. expectations of benefit.
`ailtutsrn. concerns, and general perceptions of the trial information. They also complete-d 2
`standardised questionnaires; measuring psychological morbidity and predisposition
`towards optitnistit.
`lies-tilts.
`l'orty pattcnls completed the study questionnaires. Patients were generally opti-
`n'iistic with low concerns about
`the experimental nature of Phase 1
`trials. Most 36MB
`{90%; l'DlIHF'I'I'lL-t’l m rrial entrv. Filly-one perciml: thought the trial was the only treatment
`iilillftll available. 'l‘ltt- Itiur inain ieasons for trial entry were: expectation of some medical
`mm!” [2|I}':|}_1Jilltlil'IFII-‘Hl Jamming. Uptttit‘t (219:3); to maintain hope (15%) and to help with
`rt"'.I'.t|r'l| []'J."-;.i Hul'}! imi- patjt-nt pave altruism as their main reason for trial participation.
`r'uni lll'.|tit|
`l'illll'lll‘. t'tillfilllt‘lllll',l"|li|1-'l.'
`l Illillfi maybe a sell-selected group with optimistic
`t-Mw l.lll<tll'. nl iii-i-aiital lll‘lll'lll tllWllll—L trial enlty rather than alttttistn. Achieving genu-
`I|||Iltlr Ir.j.,|.|,..,i ...,.....,.i ”I“:
`,wmilam-t- til
`therapeutic tttisconceptions in such patients;
`III-IV lii- Illlll"tlll
`
`i - Elli] illsevier Ltd. All rights reserved.
`
`“——
`
`1.
`
`Introduction
`
`Phase 1 U”) (‘lillit'fll trial-1 tiit' t'lltl'litl in llll' ilt'w'ltil’ltiitltl lll
`new anti-cancer Irnatnn-nts. New »|i:I‘ttl-t
`tlt.it
`lItIVI" shown
`promise in the li'l’Uli-llmv are risitallv ll“il|_'l'l
`ltt [Jilllt‘Hl't with
`fidVllllt-‘L‘d disea5e The aims.- ol l"I
`trial-.1 are to determine Hilll‘
`dosage range and identify side-effects.
`'l'lieuo trials convey
`small prospects ol' [hEI'i-‘PL‘UUF beiteht and carry vowing pf)".
`SilJillliE‘S 0f SidP-Oflects.'
`it
`is there-lore not sttrptising that
`recruiting patients ““0 ”1959 StUdlt-“S generates ethical do
`bate" and “Bali-‘5 Challenging communication issue-s."1
`
`A -.y-.ii‘uialir' ri-vti-w liv 't‘riilrl and colleagues ' examined the
`litihlllw aurl
`tin-pantie :Illlllltll'li ol' patients with advancith
`rain-m inwrnrlu t’l"-t'-'Il('ll. Iii
`ll'llH Il"Vlt‘W lt Hlllt'lll'S wrarc ll'llf‘ll-
`Iiltml
`lui
`i-vnllnllinit Mir-1|
`lIIWJlUt't’l
`ltvpiillielii'itl
`‘rtt't'lllllttit'.
`<lllll only two W“!!‘ with Ililllf'lllli in l’l Ititilr:
`iittn qualitative"
`and tilt“ quantitative '
`l..'tl|'tlllli‘tll motive-.-
`liti participation
`Wt.‘It_’i-Ill|ltl.‘illl, llt‘tljl'l and lot Ilt'lrlnllill lll‘lll'lll. fliatti'i'tiistalmiil
`negativvitiipai-l Utl11VIII|}lI’tlll"-illlll II.".l( [ll
`lllt'lt'Llh‘t'll lltlfillllill
`admissions emerged its masons for tlw'linitm pattii'ipatinn.
`Most patients were positive in general .iltiiiil ”rat-arch tll'HltlIt‘
`having tirlvzittr‘etl
`(lineage. Cflllt'llllilltltti wi-ti-
`llllll
`Illtllt-
`
`' {fortesponiliiit} tittlltot.‘ Address: Cancer Research UK Psychosocial Oncology (itottp. Bi ightrin ariil Hun-amt Medical Si'lttinl, llltin't'w'Ilv HI
`Sussex, Palmer, Brighton. [East Sussex I'iNl ‘JQG. UK. 'I'el.;
`i-‘l—‘l 12?? SHOE-’1; lax: Hill 1273 SHOE?
`E-tnttil adtltess: S.1,.Ciitt@SLts5iax.t'ic.ttl-: [5. Catt].
`0959-8049131; - ser- lmnl matter t 2011 Elsevit-r Ltd. All rights rcseivetl.
`dotitixtoiexjejcazot1.01020
`
`

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`was.
`-nO nlher (thrun'. AlliiiIth 11-:
`._
`.
`_
`.
`.
`.
`key drtw-I {at
`trial t‘nl'w, hut
`llll.“:1|-.‘HlllrllL't-i Kl'ltlw it
`15-; inhe-
`.
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`.
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`tecttiilu'ient.
`the tllll'lL‘LlIlIl-‘fi encrutmleretl with flIt-af'llhEuJTIg
`.
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`.
`.
`.
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`Phase um} cancel Chl'lli'zltl tl'li‘llF: have been well t1t:r_'1.rmenterl
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`lot henhhcttre proler.:~1011.-Ils
`_.
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`‘
`_
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`_
`.
`.
`.-
`successful. courses dealing with rt-CIInting i.):;lllt‘1‘llh to P3 Ill-
`1
`1
`_
`_
`Lilli have been developed and evaluated.
`Nt—tvulthf'ltSh,
`it
`_
`.
`_
`.
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`I.
`arguably requires even higher order [TOIHIIHIHIMHIOH “Lilla to
`'
`.
`.
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`_-;.
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`t11:-:l::.'
`_
`_
`_
`_
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`.
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`-
`.
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`..
`.
`patients lot whom 111th conventional 'lh'dllt'll-.lllf~- haw larhcl
`-
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`lllllLdlI‘q-l'if
`.
`.
`.
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`.'
`_‘
`_~
`expectations [or benefit. Patient
`lEILIIJIh mnltthtrnIt, In this
`.
`.
`_
`_ -. ...J-
`SilLl'clllOIl
`include cleriiugmphv,
`ith‘VlOIIH tttatmtnt Li-ipu:
`ences‘ perrtnnnlitv rruite :Jntl CLJt'H-‘I'IT phyetcnl and mental
`health. Recent
`thE‘ii'i-L1l'1i:llV'.:‘>lE-.i"‘ confirms that one-third til
`patients with cancer in acute care antler mental health prob-
`_
`_
`.
`_
`'.
`A
`.
`.
`-.
`toms that wmrnt'it ilppl'fjpllilh' lietatmenl .int‘l Illlh 1m vdlr nit
`Ls; about"
`that
`at
`the IeIeneml population. The
`IL'VPlS 01
`depression and anxiety [llE-ltjit‘lL‘tE-i Int patients wrth :ttlvuncetl
`cancer in palliative :‘t-n'i- match or when exceed those in acute-
`me.
`.
`_
`.
`.
`-
`_
`_
`,.
`.
`.
`_
`.
`._
`‘
`_
`_
`Personality trans may also illlll.It-'t1(.‘l‘ llt'dllll (it (151nm malt
`mg 30 dtt.‘ :1! interest when looking at ltlLIIHE dlliIt [1|th Ilml
`recrttttment. especmlly opttmtmn.
`the hem'ltt
`L‘t'l penilivi
`_
`.
`.
`.
`.
`.
`_I
`thinking 15 [I tmtrcm often tipplied lu lit’althi‘tllmhb and cam l
`t
`...'
`.
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`'...
`.
`by lay people and Rflt‘nt‘ healthcate piolt bHUI'ldlh. hi [hi :1
`IL
`-
`-
`-‘
`:1.
`_.
`'
`..J
`Vtew Schr-ler Lllld Ltarver
`state the ellet t5, pt Uplill‘llbll] .nt
`.
`.
`.
`.
`-
`.
`.
`..
`.
`.
`not limited lo making people leel bifl'll‘L it also i Ulllt I‘x put-d
`rive influences on what people chi and what people Ftlt' zihle tn
`achieve in times at adversity. [1 seems. reasonable therelnte [0
`pay attention to optimism when trying to nttuletstunrl
`thi-
`"
`'
`'
`—
`-
`»
`-..
`---,-
`v.-.
`.
`Ir
`(lecherous patients with iiflVdTlCt'd tan: LI mnlii.
`.‘llJULJI
`l
`l trial
`.
`.
`.
`
`.
`partitipzitimi.
`I
`.
`.
`.
`In this. descriptive paper we l'uctu; U” the reasons: palm-“nth-
`-
`_
`_ -
`‘
`.
`-
`'
`_
`.
`..
`..
`E
`..
`gave for accepting or (let lining the inwtatmn to paint-1p itc in
`1‘1 trials, their psychnlugical Well-being and plt‘dlSpUSltltlll 1r)-
`wards optimimti.
`
`___—___—
`.
`1
`2.
`Methods and matena s
`
`1
`-
`..
`..
`_
`_
`cl. Linger LRUL hmrlttl
`The data were collected as part Ul
`Rl'LIFJV‘IU
`tr_i
`improve communication lint-tween healthcnte
`
`

`

`1492
`
`i-I I'|.l'J i-Il'i'Iir‘ii
`
`It!
`
`I'
`
`.'\:'-.'" tit .13 (Jul I)
`
`tr'l'lti
`
`lip-it
`
`i
`
`'-
`
`trials. The
`professionals and patients when discussing l’l
`study had mnlti-centre ethical approval
`(tiltl'ordsl'tire Re-
`search Ethics Committee C Ref: D7/Q'lfil'tfi/PO) and all
`local
`NHS RErD permissions.
`This was a convenience sample. To reduce the risk of
`introducing selection bias, whenever researchers were pres
`cut all patients attending Clinics for a P1 trial discussion were
`approached consecutively.
`Prior to consultations patients were given an information
`sheet about the communication study to read and written in-
`formed consent was obtained. The consultation was digitally
`audio recorded, after which the researchers conducted lace
`
`to—face study specific semi—structured interviews with pa
`tients to determine patients' perspectives on what the corr-
`sultation had covered. Clinicians also con'rpleted a brief
`questionnaire probing their views on what had been dis
`cussed during the consultation. These data have been re-
`ported elsewherer'” Additionally, patients were given '3
`questionnaires to complete at home and return by post after
`they had made decisions about trial entry.
`
`2.1.
`
`Questionnaires
`
`The three questionnaires administered were, (1) clinical trial
`acceptfdecline questionnaire,
`(2) Lile Orientation 'l‘est-
`Revised (LOT- 11),“ and (3} General Health Questionnaire-l9
`itern version (Gl--[Q12).""
`
`2.1.1. Accept/decline questionnaire
`Patients' motivations for trial participation or not, were re-
`corded via a study specific questionnaire (see Appendix A)
`which was based on a design by Penman and colleagtles""
`and from previous research on the reasons patients gave lor
`joining Phase 3 trials.” The questionnaire rouse-Ned of an ini-
`tial question ascertaining th’lllf‘l or not
`the (Mllt'lll had
`agreed to trial entry. Patients were tlrt-n asked tn rule on :r
`5—point Likert scale to wlml t‘Klf‘llI
`liar-v rigrt-r-tl or tie-.ugrm-rl
`with 21 list of ’19 reasons that trnglil have nilirtt-nt ml the tll'll
`sion to either accept or declini- Ilte Irial IllUIl-Illfrll
`'l'lll‘v Illlll
`rated the most il‘nporttn'rl
`ll'Il'.Ull
`Irir
`lltl'll Elt‘l intuit -r|trl
`li-‘IIl
`the oppotlunity to mid [unlit-t t'XillilllalltrIIE. ill -lll :itltlturrtml
`box (qualitative responses). Nu ltlllltill
`Il’linltlllly ll";l|ll)'l nl
`this questionnaire is available lllll
`it
`l|.I'-t irer‘n lieu-rt
`III -.--w-t.tl
`previous studies. ""3”
`
`2.].2.
`
`LOT-ll
`
`This lU-ilem selfl'epml st'tile measures predisposition tr.
`wards opt‘irnisrrt. Validity and It‘lILIlJililV have it"l'll )Illl'tll'.llr-t_l
`and it has been applied in oncology settings. " 'l'linia- til" sax
`target statements (with :t n even mix of positive and I'IL‘HLJII‘N'
`wording), and four fillet iten'is. Respondents tine Their agree
`Inent with items on a 5-point Likert scale ranging from
`U : strongly disagree to 4 r strongly agree. Higher scores rep
`resent grealer optimism.
`
`2.'l.3. GHQ)?
`
`This is a well validated self— report measure of general psycho-
`logical well-being widely used in patient populations.” A
`score above a threshold of
`:4 is suggestive ol probable
`psychological morbidity.
`
`2.2
`
`Statistical analysis
`
`Using SPSS 16.0 lot Windowa sunnnnty slnlisli-"s vvt-tr- genet-
`;tterl tor the data: connls, percentages and :iVI-‘i'ages. A non-
`parametric correlation, Spearmnn's rho, was used to test the
`relationship between psychological well being and optimism.
`
`
`- ble 2 - Characteristics of the whole study sample.
`
` (r1 : 40)
`Sex
`Male
`Female
`
`22 (55%)
`18 (45%)
`
`Age
`Mean (SD)
`Range (min—max)
`
`Age band
`25-34
`35414
`45—54
`55—6-11
`..-.-55
`Missing data
`Marital status
`
`Partner
`No partner
`Missing data
`
`Employed
`Yes
`No
`Missing data
`Education
`
`No school exams
`tress/A Level
`University and higher
`Missing data
`Center site
`
`Cnlnrecltil/upper Cl
`llrensi
`Gynaecological
`til-tin
`Other
`l'll'lllfllll'i ll’l‘l’lll‘llfflllli
`
`Fania-rt; (ever)
`Hingle intervention
`Mitlliplt- interw-nlirilit.‘
`t'Litt-irrtrllIr-nrpy (ever)
`Single emits-.1.-
`Multiple l'{l'l|f.'il“_'.
`ltatliullitrtnpy
`l-lortrione
`
`Preuioas trial experience
`Yes
`Missing data
`snow
`Above threshold (case)
`Below threshold
`Missing data
`LOT-R scores
`
`Mean (S.D.)
`
`Range (min—max)
`
`53.8 (11.10)
`29- 76 years
`
`3 (3%)
`1 (3%)
`a {20%)
`15 (38%)
`12 {31%)
`1
`
`28 (72%)
`11 (28%)
`1
`
`9 (23%)
`30 (77%)
`1
`
`13 (33%)
`1.2 {31%}
`14 (36%)
`‘1
`
`22 (55%)
`5 (15%}
`5 (13%)
`3 (8%)
`4 (10%)
`
`32 (arm;
`20 (50%)
`12 (30%}
`‘m (95%)
`z {12%}
`’ll tram
`l 9 rill-z.)
`2 tot.)
`
`Ill (4 6%)
`'1
`
`[at as.)
`1 (i
`:to [s i it.)
`1
`
`15.45 (3.023)
`3—24
`
`

`

`
`
`3.
`
`Results
`
`3. l.
`
`Sampli-
`
`r :lIIi I'l rI‘iIliI“: [HI-illtuni
`lll't'ltlllllli'lli llltll". plut'v ll-rlll llUI‘ |l|'-.'.
`i'iiir_'ri|iii;y l.I'1l|I".
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`HUVIII
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`.nirl
`litizlrnrl
`tili-
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`lat-tw-wu nit-,[nst
`L’itui’
`illltl
`Ilr't't‘liiiwt'
`ill-Jill”.
`
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`jnili
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`ill
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`[ml ”in [r'lirlll nut-luliiinnriilvs, fivu wmi- l;;l.ll').‘il'(]lll‘l|llV lll*_‘l|t‘ll-
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`:ivnilnhli- ll'n 4U puttiriimnlr;
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`i'luuzn‘lnitntirzi, nncl 'lnlili- 'l sin-i il]n_'>'. fit the ltiuls: I:ll.'5iE'LlS!.+t'E.l.
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`[1.05 lL‘Vlz‘l.
`21:1ilorl, n :5”), nut: pnlii‘ut
`[litl nut
`('Ulllplt‘lt'
`llltr
`(illQllf.
`I]ll".‘l$'-ll|t’.‘}, witlt lnwi-r nuliinisi'n :15:50I.‘i‘ril0rl willt instantiate in:
`pmlmlili- IJHYL'lIlJltJfllrill rumbirlily.
`
`"
`
`|.-‘l'rlli;il.1-.ii
`
`“1.3:.
`
`1493
`
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`|Jilill'lilI-i :n.'r..'I_'_[.in_-ri will i
`(tin-i .'ill_ "lit-"rill [‘.it.]'.i.'._l
`lIi.i|'-'-. [1|th"U411[till-i.)rlr-i'linvil.;i Illllllllt‘]
`lrm :-;|lli|ll hit
`:Iilv
`'tiilll‘wlll .il
`il||§il\r".':lii
`'l'lu'u’ Iii-i'lil'ii:'r:-:' JInInc'lviiHlii'n illl‘ flit-1-
`
`i'li‘i'isinn :in- [lit-'-
`l:.‘-.']1lii|t.ll|l=|1-4 lin tlu-JI
`in 'I‘nhlv rl.
`iitnvi-i'l
`lit-‘lnw in. full
`intuit-s.
`lrrnu lllt' qnnlitntit'r- li_‘*i]1IJ|l‘iE_-!-i
`Ht'llll’ll
`tum-ii nu tlir- :Ii'rqtli’ilrn lim- 1']Iti.':-.'llullllilllt'.
`'l‘liii i-xplnnulitnis
`l.:l\“.‘|l
`ilii'lntflu- :gunlit.v Ill
`lilu': Linus-trim.‘-Iti-:Jn:;:, inhm [lL‘i—llllll‘il'
`nptinns, unii linit~ constraints-1
`
`3.2.
`
`Qualitative responses given by trial decliners
`
`l‘lnw l'Iilt.‘l( with my lllltilli'il‘lt'l
`lJiIfL‘ll living on my i'iwn.
`1D 15.
`”W51I'“""l'll:‘.l;i:'icl:tn Walt-s tn I'nnku llll‘ must {11' whulwt-t linw
`lhnvt‘ It‘ll.
`
`It} 20. Dnnlitv Lil lilo is 1:u' tuuri' iinpmtnnl lllilll.flll(l|l[ll\,1I Ul
`lllE‘.
`
`| th’L'lle‘ll lo hurnmta n privnlt‘ pnlir‘nl and have 11 drug
`1D 44.
`not :ivnilnblu nu lllt’ Ni 15 in] n ll.‘W months. As in whut‘he: this
`wns nl benefit, l would t'c—cnnsii'lt’i n Iiiinl if nl'lun-Jtl Lil n lull-"I
`
`flitti.’ .nti'l assuming the drug I nut inking is ItitSLitK‘L‘SHIttl. 'l'inw
`will ll‘ll.
`
` {n .- 40}
`
`type of trial discussion
`1? (30%}
`General discussion
`10 (25%}
`Dost.- escalation study
`it (27.5%}
`‘l'mgeti11g/nntibuclw'inu'nimntlItflt'npg,l
`{im'nbinntiou (standard theme plus new agent} F (118%)
`
`liliLTll‘llftl that this itnt'tit'ulnt li'inl UULL'J' vow intense :11an
`ID 60.
`that th‘ tr'uvvlling would put lriu gut-nl {l st I uin int hnlh ittvSIL‘ll
`nnrl my hushnnd. 'l'hm'v's nnolht‘l [i'ltll in August: which is nut
`50 lllll‘l'lSlT‘ which l'iupvlullv will wml:
`in the snnw w-"IV lllll'
`with lE‘WPl visits.
`
`'l‘rml agent
`Nnr'tla discussed {gt-:rieial discussion}
`Cytotoxic i'll‘ld/IOI' untiInuhlornlive
`Monoclonal antibody
`“lyinsiiit‘ kinnse inhibitor
`Angingnnesis inliiluitm‘
`DNA i'r?pnii' inhibitor
`Vnt'citie
`Cilher
`
`llniitr.‘ of Lulu-iinistrution
`Noun discussed {general disrussiou}
`(lint only
`tnlruvr‘nuus only
`tntrurnilsmlnr only
`Intrnvmmns and oral
`
`llltspt'r‘iliet'l
`
`able 4 - Decliner characteristics.
`
`12 {30%}
`is {-12.13%}
`3 (15%}
`r {115%}
`4 (10%.)
`'5 (112.5%)
`2 (5%)
`'3 {5%}
`
`12 (30%)
`l2 [30.3.01]
`L) (22.5%]
`'3 {5's}
`4 (10%)