`
`Vol. 18, No. 12, December 2013
`
`Oncologist.
`v. 18, no. 12 (Dec. 2013)
`Seneral Collection
`1 ON105AM
`
`>014-02-03 10:06:01
`
`Ee
`
` gist
`
`The International Peer-ReviewedJournal for thePracticing Oncologist/Hematologist
`
`CANCER PREVENTION
`
`REVIEW ARTICLE
`
`|
`|
`
`|
`
`f
`h
`
`ls
`Metformin Is Associated With Survival
`Benefit in Cancer Patients With Concurrent Type 2
`Diabetes: A Systematic Review and Meta-Analysis
`Ming Yin, Jie Zhou, Edward J. Gorak et al.
`Commentary: Carlo La Vecchia, Cristina Bosetti
`
`bibepasicsh Pena thserers
`ae ee
`Metronomic Capecitabine in Advanced
`Hepatocellular CarcinomaPatients: A PhaseII Study
`;
`j
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`2
`1
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`Valentine rea Francesco de Rosa,
`Jalentina Apostini
`et
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`Adjuvant Therapy for Adenocarcinomaofthe Lung
`Rebecca Heist, ¢ histopher G. Azzoli
`/
`Expo RINOLOGA
`
`Sd
`
`Clinical Efficacy of Targeted Biologic
`Agents as Second-Line Therapy of Advanced
`Thyroid Cancer
`Taoteek K, Owonikoko, Rajasree P. Chowdry,
`Zhengjia Chen et al.
`ROINTESTE
`ESTISAL CANCER
`WASIR
`a
`Impact of Molecular Alterations and Targeted
`Senet
`.
`:
`Therapy in Appendiceal Adenocarcinomas
`7
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`Kanwal P.S. Raghav, Aditya V. Shetty,
`Syed M.A. Kazmiet al.
`GLOBAL HEAL AND CENTER
`Screen-and-Treat Approach to Cervical Cancer
`Prevention Using Visual Inspection With Acetic Acid
`and Cryotherapy
`Proma Paul, Jennifer L. Winkler,
`Rosario M. Bartolini et al,
`
`(
`
`
`
`1285 Advancing Cervical Cancer Prevention in India:
`ImplementationScicnce Preiss
`Suneeta Krishnan, Emily Madsen,
`DeborahPorterfield et al.
`
`(298 Breast Cancer in Young Women in Latin America
`Cynthia Villarreal-¢ UE ea Aguila,
`Maria C. Magallanes-Hoyos etal.
`:
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`GYNECOLOGIC ONCOLOGY
`%
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`(307 Anti-Miillerian Hormoneand AntralFollicle Count
`serve
`i
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`Reveal a Late Impairment of Ovarian Reserve In
`Patients Undergoing Low-Gonadotoxic Regimens for
`Hematological Malignancies :
`ar
`Rossana Di Paola, Claudio Costanunt,
`Cristina Tecchio et al.
`
`|
`
`a re a
`tenn RE
`(415. Barriers to Study Enrollmentin Patients
`With AdvancedCancer Referred to a Phase |
`Clinical Trials Unit
`Siqing Fu, LaceyMcQuinn, Aung Naingetal.
`’
`‘
`"AR
`:
`SYMPTOM MANAGEMENT AND SUPPORTIVE CARI
`att
`som
`Risk
`in
`Patients With
`13:
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`boembolismRisk in Patien
`bho Adee = Chemotherapy: A Real-World
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`Analysis
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`Gary H. Lyman, Laurent Eckert, Yanxin Vang
`Che’
`
`
`IN MEMORIAM
`— ————————
`| $32
`In Memoriam: MichaelJ. Haut
`
`
`
`Ihe official journal of the
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`ThG
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`Access TheOncologistCMEOnlineat
`articlesavailableforcontinuingmedical
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`education credit in this issue.
`
`CME.TheOncologist.com for a total of 3 new
`
`— V
`
`olume 18, Number 12, December 2013
`
`“ex Indicates online-onlyarticle
`
`COMMENTARY
`
`1245 Metformin: Are Potential Benefits on Cancer Risk Extended to CancerSurvival?
`Carlo La Vecchia, Cristina Bosetti (see article on page 1248)
`
`CANCER PREVENTION
`
`Section Editor: Powel H. Brown
`
`CME
`
`1248 Metformin Is Associated WithSurvival Benefit in Cancer Patients With Concurrent Type 2
`Diabetes: A Systematic Review and Meta-Analysis
`MingYin,Jie Zhou, Edward J. Gorak, Fahd Quddus (see commentary on page 1245)
`
`CLINICAL TRIAL RESULTS
`
`— .
`Section Editors: Susan E. Bates, Antonio Tito Fojo
`
`1256 Metronomic Capecitabine in Advanced Hepatocellular Carcinoma Patients: A PhaseII Study
`Giovanni Brandi, Francesco deRosa, Valentina Agostini, Stefania di Girolamo, Pietro Andreone, Luigi Bolondi,
`Carla Serra, Claudia Sama,Rita Golfieri, Annagiulia Gramenzi, Alessandro Cucchetti, Antonio Daniele Pinna,
`Franco Trevisani, Guido Biasco,for the ITALIAN LIVER CANCER(ITA.LI.CA) GROUP
`
`CHALLENGING CASES
`
`;
`Section Editor: David P. Ryan
`
`1258 AdjuvantTherapy for a 3.9-cm Adenocarcinomaof the Lung
`Rebecca Heist, Chistopher G. Azzoli
`
`ERGAERINGLOSY
`
`Section Editors: Herbert Chen,Stan B. Sidhu
`
`at
`
`1262 ClinicalEfficacy of Targeted Biologic Agents as Second-Line Therapyof Advanced Thyroid Sanne
`Taofeek K. Owonikoko, Rajasree P. Chowdry, Zhengjia Chen, Sungjin Kim, Nabil F. Saba, Dong M.Shin,
`Fadlo R. Khuri
`
`GASTROINTESTINAL CANCER
`
`oo
`;
`Section Editors: Richard M. Goldberg, Patrick G, Johnston, Peter J. O'Dwyer
`1270 Impact of MolecularAlterations and Targeted Therapy in Appendiceal Adenocarcinomas
`anxiang Zhang,Jeffrey Morris, Melissa Taggart,
`Kanwal P.S. Raghav,Aditya V. Shetty, Syed M.A. Kazmi, Ni
`ichael J. 0
`Keith Fournier, Richard Royal, Paul Mansfield, Cathy Eng, RobertA. Wolff, Michael
`J. Overman
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`GLOBAL HEALTH AND CANCER
`
`Section Editors: Felicia M. Knaul, Rifat Atun, Eduardo Cazap
`
`1278 Screen-and-Treat Approach to Cervical Cancer Prevention Using Visual Inspection With Acetic
`Acid and Cryotherapy: Experiences, Perceptions, and Beliefs From Demonstration Projects in
`Peru, Uganda, and Vietnam
`Proma Paul, Jennifer L. Winkler, Rosario M. Bartolini, Mary E. Penny, Trinh Thu Huong, Le Thi Nga,
`Edward Kumakech, Emmanuel Mugisha, Jose Jeronimo
`
`1285 Advancing Cervical Cancer Prevention in India: Implementation SciencePriorities
`Suneeta Krishnan, Emily Madsen, Deborah Porterfield, Beena Varghese
`
`1298 Breast Cancer in Young Womenin Latin America: An Unmet, Growing Burden
`Cynthia Villarreal-Garza, Christian Aguila, Maria C. Magallanes-Hoyos, Alejandro Mohar, Enrique Bargallo,
`Abelardo Meneses, Eduardo Cazap, Henry Gomez, Lizbeth Lopez-Carrillo, Yanin Chavarri-Guerra,
`Raul Murillo, Carlos Barrios
`
`GYNECOLOGIC ONCOLOGY
`
`Section Editors: Dennis S. Chi, Peter G. Harper
`
`1307 Anti-Millerian Hormoneand Antral Follicle Count Reveal a Late Impairmentof Ovarian
`Reservein Patients Undergoing Low-Gonadotoxic Regimens for Hematological
`Malignancies
`RossanaDi Paola, Claudio Costantini, Cristina Tecchio, Gian Luca Salvagno, Rachele Montemezzi,
`Alessio Perandini, Giovanni Pizzolo, Stefano Zaffagnini, Massimo Franchi
`
`OUTCOMES RESEARCH
`
`CME
`
`1315 Barriers to Study Enrollment in Patients With Advanced CancerReferred to a Phase| Clinical
`Trials Unit
`
`Siqing Fu, Lacey McQuinn, Aung Naing, Jennifer J. Wheler, Filip Janku, Gerald S. Falchook,
`Sarina A. Piha-Paul, Dennis Tu, Adrienne Howard, Apostolia Tsimberidou, Ralph Zinner, David S. Hong,
`Razelle Kurzrock
`
`Section Editors: Scott Ramsey, Bong-Min Yang
`
`SYMPTOM MANAGEMENT AND SUPPORTIVE CARE
`
`1321 Venous Thromboembolism Risk in Patients With Cancer Receiving Chemotherapy: A Real-World
`Analysis
`Gary H. Lyman, Laurent Eckert, Yanxin Wang, Hongwei Wang, Alexander Cohen
`
`Section Editors: Eduardo Bruera, Russell K. Portenoy
`
`LETTERS TO THE EDITOR
`
`1330 Comprehensive Geriatric Assessment and Adjustmentof Cancer Treatment
`Monique S. Slee-Valentijn, Andrea B. Maier
`
`1331 InReply
`Nadine J. McCleary, Arti Hurria, Jeffrey Meyerhardt
`
`

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`In MEMORIAM
`
`1332 InMemoriam: Michael J. Haut
`
`1334 Volume 18 Acknowledgments
`
`1336 Volume 18 Author Index
`
`EUROPEAN PERSPECTIVES
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`) e29 Addressing CancerDisparities in Europe: A Multifaceted Problem That RequiresInterdisciplinary
`Solutions
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`Sean Duffy, Mike Richards, Peter Selby, Mark Lawler
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`Thencologist’
`
`Barriers to Study Enrollmentin Patients With Advanced Cancer
`Referred to a Phase| Clinical Trials Unit
`
`SIQING Fu,” LACEY MCQUINN,” AUNG NAING,” JENNIFER J. WHELER,"FILIP JANKU,” GERALD S, FALCHOOK,”
`SARINA A. PIHA-PAUL,” DENNIS TU,” ADRIENNE HOWARD,” APOSTOLIA TSIMBERIDOU,” RALPH ZINNER,” DAVID S. HONG,”
`RAZELLE KURZROCK”
`"Departmentof Investigational Cancer Therapeutics (Phase| Clinical Trials Program), The University of Texas MD Anderson Cancer Center,
`Houston, Texas, USA; "University of California San Diego Moores Cancer Center, La Jolla, California, USA
`Disclosures of potential conflicts of interest may be found at the end of this article.
`Key Words. Phaseltrial * Enrollment
`* Consults * New patients * Patient referral
`
`+ Barrier
`
`Learning Objectives
`Discuss strategies to improve therate of enrollment of cancerpatients in phase|trials.
`
`Assess barriers for advanced cancerpatients to participatein phase| trials.
`
`ABSTRACT
`
`Background. We conductedthis retrospective study to iden-
`tify reasons that patients referred to a phase| clinical trial
`failed to enroll or delayed enrollment onto thetrial.
`Materials and Methods. Outcomeanalyses were conducted
`independently on data collected from electronic medical
`records of two sets of consecutive patients referred toa
`phase| clinical trial facility at MD Anderson Cancer Center.
`Data from thefirst set of 300 patients were used to deter-
`mine relevant variables affecting enrollment; data from the
`second set of 957 patients were then analyzed for these
`variables.
`Results. Results from the two sets of patients were similar. Ap-
`proximately 55% of patients were enrolled in a phase| trial.
`Patients referred from within MD Anderson were morelikely
`to be enrolled than patients seen originally outside theinsti-
`
`tution (p = .006); black patients were morelikely than
`white patients to enroll (69% vs. 43%; p = .04). The median
`interval from the initial visit to initiation of treatments was
`19 days. Major reasons forfailure to enroll included failure
`to return to the clinic (36%), opting for treatment in an-
`other clinic (17%), hospice referral (11%), early death
`(10%), and lackoffinancial clearance (5%). Treatment was
`delayed for three weeks or more in 250 patients; in 85 pa-
`tients (34%), the delay was caused byfinancial and insur-
`ance issues.
`Conclusion. Failure to return to the clinic, pursuit of other
`therapy, and rapid deterioration were the major reasons for
`failure to enroll; lengthy financial clearance was the most
`commonreasonfor delayed enrollment onto a phase| trial.
`The Oncologist 2013;18:1315-1320
`
`implications for Practice: Early drug developmentis essential as a first step in guiding the developmentof cancer therapies.
`Therefore,sufficient enrollment of patients into phase| clinical trials in a timely fashionis key to facilitating cancer drug investi-
`gation. Wepresenttheresults of a study designedto investigate barriers to study enrollment in patients with advanced cancers
`referred to a phase| clinicaltrials unit. Careful coordination between referral and phase | services may result in the referral of
`appropriate patients, thus increasing the rate ofstudyenrollment. In addition, overcoming potential financial hurdles maysignif-
`icantly helpfacilitate rapid enrollment.
`
`INTRODUCTION
`
`_
`
`:
`
`Patients with advanced refractory cancerare eligible to partic-
`ipate in phase| trials [1]. Recently, we demonstrated that pa-
`tients who werereferred to the phase| clinical trials program
`at MD Anderson Cancer Center had a median overall survival
`of approximately 10 monthsafter referral [2]. Sick patients
`may do considerably worse (mediansurvival of 3.2 weeksaf-
`ter initial intensive care unit admission and one day after re-
`ceiving cardiopulmonary resuscitation)
`[3]. Options for
`
`patients whosediseasehas failed to respond to conventional
`treatments may include seeking complementary approaches
`[4], hospice care, or participatingin a clinicaltrial [5-7].
`A meta-analysis spanning eleven years of patients with
`cancer enrolled ina phase| trial reported an overall combined
`complete andpartial response rate of 11%. An additional 34%
`of patients demonstrated less than a partial responseorstable
`disease [1, 6]. Despite the potential benefit of participatingin
`
`Correspondence:Siging Fu, M.D., Department of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer
`Center, 1515 Holcombe Boulevard, Houston, TX 77030, Telephone: 713-792-4318; Fax: 713-745-3855; E-Mail: siqingfu@mdanderson.org Re-
`ceived June 6, 2013; accepted for publication September 24, 2013;first published online in The Oncologist Express on October 23, 2013.
`©AlphaMedPress 1083-7159/2013/$20.00/0 http://dx.doi.org/10.1634/theoncologist.2013-0202
`
`—
`
`The Oncologist 2013;18:1315-1320 www.TheOncologist.com
`
`©AlphaMedPress 2013
`
`
`
`|
`|
`
`|
`|
`
`

`

`1316
`
`Barriers to Enrollment in Phase | Trials
`
`a phase| trial, patients who are seen in a facility conducting
`time of data analysis were censored at that time (July 31,
`phase| clinical trials may have enrollment delayed or may not
`2012) if they had not been enrolled into a phase| trial. All pa-
`be ableto participatein a trial or may choose nottoparticipate
`tients referred to the phase| clinical trials facility during the al-
`[8, 9]. Enrollment delay may result in ineligibility of patients
`lotted time were included in the analysis, regardless of
`for a specific phase | trial because of continuous tumor pro-
`whether they received treatment. The chi-square test or
`gression-related systemic effect. To investigate timelines and
`Fisher exact test were used to examine the association be-
`factors affecting enrollmentinto phase| clinical trials after re-
`tween two categoric variables. Statistical inferences were
`ferral, we undertookthe presentstudy.
`based on two-sidedtests at a significance level of p < .05. Sta-
`tistical analyses were carried out using GraphPad Prism5soft-
`MATERIALS AND METHODS
`ware (GraphPad Software,Inc., San Diego, CA, http://www.
`graphpad.com).
`
`RESULTS
`
`Patient Selection
`Two sets of consecutive candidate patients with cancer who
`werereferred to or came as new patients to the Department
`of Investigational Cancer Therapeutics (phase| clinical trials
`Study Patient Population
`program) at The University of Texas MD Anderson Cancer Cen-
`Between August1, 2011, and February 29, 2012, atotal of 957
`ter (MDACC) wereincludedin this retrospective chart-review
`patients with advanced cancer wereseen at the phase| clinic
`study. Data from thefirst set of 300 patients were reviewed
`at MDACC (Table 1). Of these, 803 (84%) were referred from
`from December31, 2010, backward, followed by the otherset
`inside MD Anderson, and 154 (16%) were new patientsre-
`of 957 patients who werereferred to the phase| clinicaltrials pro-
`ferred from outside theinstitution. All patients were evalu-
`gram from August 1, 2011, to February 29, 2012. Two separate
`ated and then given information aboutapotential phase| trial
`reviewers reviewedthe charts independently for each set of pa-
`if they wereeligible. Their median age was58 years old; 12.5%
`tients. Approximately 5% of the patients were randomly selected
`of patients were 70 years or older (n = 120), and 0.6% were
`for cross review to confirm accuracy. Any disagreement between
`children 18 years or younger (n = 6G). There were more women
`the reviewersor any uncertainty was broughttoajoint chart re-
`(n = 527; 55%) than men. In this cohort of patients, 76% were
`view with the corresponding author to reach an agreement. Data
`white (n = 728), 10% were Hispanic (n = 99), 9% were black
`from thefirst set of patients were usedasa training dataset to de-
`(n = 89), and 5% wereother (n = 41). The majority of patients
`termine variables that might affect enrollment. Data from the
`had gastrointestinal cancer (n = 281; 29%), gynecologic malig-
`secondset of patients were validated using the samevariables.
`nancies (n = 160; 17%), breast cancer (n = 94; 10%), sarcoma
`This study was conducted in accordance with the MD Anderson
`(n = 87; 9%), head and neck cancer (n = 82; 9%), lung cancer
`institutional review board guidelines.
`(n = 82; 9%), ormelanoma(n = 50; 5%). Significantly more pa-
`tients with gastrointestinal cancer and melanoma werere-
`ferred to the phase| clinical trials facility as new patients than
`those with other malignancies, who were mainly referred
`from the inside MD Anderson (p < .0001).
`
`Data Collection
`Clinical information was extracted from the electronic medi-
`cal records at MDACC. All patients were followed until July 31,
`2012, or death. Variables collected included age, gender, race,
`residence, time of the initial phase | clinic visit, time of the
`Enrollment of the Referred Patients Into Phase|Trials
`therapy under the first phase | clinical trial, reasons for lack of
`Initially, we reviewed data from 300 patient charts from De-
`participation, and timeof death. Reasons for lack of participa-
`cember 31, 2010, backward as a pilot study to identify various
`tion in a trial were categorized as follows: (1) death before
`factors that contribute to delay in or lack of participation in
`starting protocol treatment or before enrollment; (2) need for
`phase| trials and to determine the timelag from initial office
`referral to hospice care; (3) patient declined participation for
`visit (time of initial phase | clinic visit) to the first dose on a
`any reason; (4) ineligibility for a phase | study because of poor
`phase| trial (time of therapy). Among these 300 patients, 151
`performance status, comorbidity, and/or abnormal labora-
`(50.3%) received therapyin a phase| trial. Median time from
`tory tests; (5) financial reasons for lack of participation (e.g.,
`referral to first dose was 21 days, Patients who received ther-
`insurance would not cover or lack of adequate insurance); (6)
`apy under a phase | clinical trial after referral had a median sur-
`perceived preferable treatment options, including standard
`vival of 282 days, compared with 161 days for those who had
`therapy or phase Il orIll trials; (7) off-protocol treatmentin the
`not enrolled ina phase| trial (p—.01), This was true (289 days
`phase | clinic; (8) patients did not return, preferred to be
`vs. 196 days; p —
`.007) even whenpatients who died within 30
`treated outside MDACC, or unknown. If more than one cate-
`daysof the initial visit to the phase| trials facility were re-
`pory applied, the patient was assigned tothe single best cate-
`moved fromthe analyses.
`gory using the following rule: If the patient had reasons 2, 4,
`After exploratory analysis of data from the above 300pa-
`and 5, the patient was assigned to category 2 (the smallest
`tients, we conducted an independent chart review of data
`number). The data were entered into a Microsoft Excel data
`from 957 patients seen at the phase | clinical trials facility be-
`sheetfor further statistical analyses.
`tween August 1, 2011, and February 29, 2012. Of 957 referred
`Statistical Analyses
`patients, 527 patients (55%) were enrolled into phase|trials,
`-
`Categoric data were described using contingency tables. Con-
`The median time from the first visit to the first treatment ina
`tinuously scaled measures were summarized with descriptive
`phase| trial was 19 days(interquartile range of 14—30 days),
`statistical measures(i.e., median with range), whereas overall
`Further analyses showed nosignificant differences in age,
`survival rates were estimated using the Kaplan-Meier method
`gender, pathologic diagnosis, and geographic residence be-
`and comparedusing the log-rank test. Patientsstill alive at the
`tween patients who enrolled in a phase | trial and those who
`
`©AlphaMed Press 2013
`
`Ohicologist
`
`

`

` Fu, McQuinn, Naing et al.
`
`
`Table 1. Patient characteristics (n = 957)
`
`Enrolled Notenrolled
`Characteristic
`n=527(55%) n= 430(45%) pvalue*
`
`
`Age(years)
`Median (range)
`Gender
`
`Men
`Women
`Racedistribution
`
`58
`(17-84)
`
`57
`(17-79)
`
`234 (54%)
`293 (56%)
`
`196 (46%)
`234 (44%)
`
`74
`
`387 (53%)
`61 (69%)
`56 (57%)
`23 (56%)
`
`341 (47%)
`28 (31%)
`43 (43%)
`18 (44%)
`
`105
`
`Off-Protocol
`Treatment in the
`Phase | Clinic
`10%
`
`1317
`
`Reasonsthat Cancer Patients Did Not Participate
`in Phase | Trials (n = 430)
`
`Did Not Return
`
`36%
`Treatment at
`“
`other MD
`
`~_Anderson clinics
`17%
`
`—_ Financial
`Reasons
`5%
`
`
`
`
`
`Not Interested
`6%
`
`_Ineligibility
`6%
`
`White
`Black
`Hispanic
`Others
`Hospice 11% /
`Cancer diagnoses by
`Figure 1. Pie chart shows percentages ofpatients with cancer
`subspecialty
`whowerefirst seen in the phase|clinical trials facility at MD An-
`Gastrointestinal
`154 (55%)
`127 (45%)
`AG
`derson Cancer Centerfrom August1, 2011, to February 29, 2012,
`Gynecologic
`90 (56%)
`70 (44%)
`according to reasonforfailure to enroll onto a phase! clinicaltrial,
`Breast
`51 (54%)
`43 (46%)
`A total of 430 of 957 patients failed to enroll.
`Sarcoma
`55 (63%)
`32 (37%)
`Thoracic
`48 (59%)
`34 (41%)
`Head and neck
`47 (57%)
`35 (43%)
`Melanoma
`22 (44%)
`28 (56%)
`Genitourinary
`23 (59%)
`16 (41%)
`Endocrine
`14 (50%)
`14 (50%)
`Neurologic
`11 (44%)
`14 (56%)
`Dual primary
`7 (58%)
`5 (42%)
`Unknown primary
`3 (30%)
`7 (70%)
`Hematologic
`2 (29%)
`5 (71%)
`Status of patients
`Referred from inside 458 (57%)
`MD Anderson
`85 (55%)
`New patients”
`69 (45%)
`" pvalues are for enrolled versus nonenrolled patients.
`» New patients are those referred from outside MD Anderson.
`
`006
`
`345 (43%)
`
`phaseI clinical trial; 430 of these did not participate ina phase
`| trial. The following were the most frequent reasonsforfail-
`ure to enroll: (1) patient did not return to phase | trials clinic
`(36%), (2) patient opted for treatmentin another MD Ander-
`son clinic (17%), (3) patient accepted hospice referral (11%), or
`(4) patient died (10%)(Fig. 1). Only 5% of the patients who
`were not enrolled in a phase| trial failed to enroll because of
`financial issues, and only 6% werenot enrolled because they
`wereineligible.
`Reasonsfor Delayed Enrollment and Treatment ina
`Phase| Trial
`Further analysesof data from our cohort of 957 patients iden-
`tified 250 patients in whom treatment was not initiated
`for three weeks or longer. The median interval from the first
`visit to the phase| trialclinic to thefirst dosing ina phase| clin-
`ical trial in this cohort of patients was 30 days. Compared with
`those whoreceived their first dose in a phase| trial within
`three weeksaftertheir initial phase | clinic visit, the cohort of
`did not. Significantly more patients referred from inside MD
`patients whoreceivedtheir first dosing three weeks from the
`Anderson (458/803; 57%) participated in phase| trials than
`first office visit or beyond showednosignificant differences
`those referred from outside (69/154; 45%; p = .005). White
`with regard to age, gender,race, or pathologic diagnoses. We
`patients werelesslikely to be enrolled in phase| trials than
`foundthat the major reasonfor enrollmentdelay was that the
`nonwhites (p = .04), and black patients were morelikely to be
`business office needed extra time for financial clearance (n =
`enrolled (61/89; 69%) in phase| trials than nonblacks (466/
`85; 34%) (Fig. 2). Additionally, enrollment was delayedif the
`868; 54%; p = .007). Eight of the nine patients who were =80
`patient required extra timeifinitial tests were abnormal (n =
`years old were referred from inside MD Anderson; all nine pa-
`25; 10%), if the patient was admitted for acute medical illness
`(n = 24; 10%), orif the patient was receiving concurrent ther-
`tients were enrolled in phase | trials.
`apythatdid notallow theinitiation of the phase|trial (n = 21;
`ReasonsforLack of Participation in a Phase| Trial
`8%). Finally, the need for additionaltime to arrange traveling
`Theinitial chart review of data from 300 patients revealed the
`and/or relocation delayed enrollment for 19 patients (8%).
`following reasons forfailure to enroll in a phase| trial: (1) pa-
`tient did not return to the phase| trial clinic (23%); (2) patient
`DISCUSSION
`wastreated in another department at MD Anderson (21%); (3)
`The objective of phase| trials is to define dose levels and tox-
`patient wasnoteligible for a phase| clinical trial (20%); (4) pa-
`icity of new agentsor combinations, describe responses, and
`tient received planned hospice care (11%); (5) financial issues
`evaluate pharmacokinetics and pharmacodynamics of new
`(10%); (6) patient was not interestedin participating ina phase
`agents. Phase| trials are associated with a toxicity-related
`| trial (7%); (7) patient was treated off protocolin the phase|
`mortality of only 0.49%, and objective response rates gener-
`trial clinic(7%); or (8) patient died before starting a phase|trial
`ally range from 4% to 10% [1,6, 10]; however, higher response
`(2%). A total of 957 consecutive patients were referred to a
`
`www.TheOncologist.com
`
`©AlphaMedPress 2013
`
`

`

`1318
`
`Barriers to Enrallmentin Phase| Trials
`
`Reasonsthat CancerPatients Delayed
`the First Dosing 23 Weeks (n = 250)
`Radiation Therapy, Personal Holiday
`a%
`\
`Oh,
`_- Unknown
`10%
`
`Seeking Other_
`
`Options
`a6
`‘
`
`Pending Spot _
`A
`3%
`
`Biopsy
`-
`3%
`
`=
`
`ae
`fe ne
`/
`
`
`_ Financial
`34%
`
`Laboratory
`______ Clearance
`10%
`
`Decision-making —”
`3%
`Chemotherapy _/
`Washout
`Yo
`
`ronto, which reported an enrollmentrate of 29% [9], and 51%
`of patients referred from inside Daniel den Hoed Cancer Cen-
`ter in Rotterdam, which reported an enrollment rate of 44%
`[26]. Patients referred from inside the institution were more
`likely to be enrolled into a phase| trial, perhaps because of
`physicians’ familiarity with the requirements of these phase
`I trials. Other possible reasons include that the clinic was
`highly specialized, with physicians engaged exclusively in
`phase | clinical trials, and the presence of dedicated ancil-
`lary assistance, including nurses, study coordinators, and
`business office personnel, who focused exclusively on sup-
`porting patients on these trials. Furthermore, patients
`were prescreened bya nurse, who helped them understand
`the demands of these trials and tried to ensure that pa-
`tients who weretooill to participate knew it was unlikely
`that they would beeligible. Our pre-referral screening pro-
`cess ensured that patients who wereunlikely to meeteligi-
`bility criteria were not referred to our phase| trial facility;
`thus, our participation rate was higher than centers where
`moresignificant numbersof patients did not enroll because
`of ineligibility.
`Our findings should include several considerations. As is
`alwaysinherentto retrospective methodology, selection bias
`maylimit the generalization ofour findings. Furthermore, the
`rates of more than 20% to 30% can be seen with molecular
`matching of patients with drugs [7, 11-14]. Therefore, partic-
`actual rea