timing of palliative care referral and symptom burden in phase 1 cancer patients : a retrospective...

Timing of Palliative Care Referral andSymptom Burden in Phase 1 Cancer PatientsA Retrospective Cohort Study

David Hui, MD1; Henrique Parsons, MD2; Linh Nguyen, MD1; Shana L. Palla, MS3; Sriram Yennurajalingam, MD1;

Razelle Kurzrock, MD2; and Eduardo Bruera, MD1

BACKGROUND: Phase 1 trials offer patients with advanced cancer the opportunity to pursue life-prolonging cancer

treatments. In the current study, the timing of referral and symptom burden between patients referred to palliative

care by phase 1 oncologists and those referred by non-phase 1 oncologists were compared. METHODS: All 57 patients

with advanced solid tumors who were referred by phase 1 oncologists to the palliative care outpatient clinic at The

University of Texas M. D. Anderson Cancer Center (MDACC) between 2007 and 2008 were included. The comparison

cohort was comprised of 114 non-phase 1 patients who were stratified by age, sex, and cancer diagnosis in a 1:2 ratio.

Information regarding patient characteristics, Edmonton Symptom Assessment Scale (ESAS), timing of referral, and

survival was retrieved. RESULTS: Both cohorts had the following matched characteristics: average age of 57 years,

with44% of the patients being female and 47% having gastrointestinal cancers. At the time of palliative care consulta-

tion, patients referred by phase 1 oncologists were more likely than patients referred by non-phase 1 oncologists to

have a better performance status (Eastern Cooperative Oncology Group 0–1: 61% vs 36% [P ¼ .003). The ESAS was

not significantly different with the exception of better well-being in the phase 1 cohort (mean, 4.5 vs 5.5; P ¼ .03). No

difference was found for the duration between registration at MDACC and palliative care consultation (13 months vs

11 months; P ¼ .41) and overall survival from the time of palliative care consultation (5 months vs 4 months; P ¼ .69).

CONCLUSIONS: Outpatients referred to palliative care by phase 1 oncologists were found to have a better perform-

ance status but similar symptom burden compared with patients referred by non-phase 1 oncologists. Patients with

phase 1 involvement did not appear to have delayed palliative care referral compared with non-phase 1 patients. The

results of the current study support the development of a simultaneous care model. Cancer 2010;116:4402–9. VC 2010

American Cancer Society.

KEYWORDS: advanced cancer, palliative care, phase 1, referral timing, simultaneous care, symptoms.

Patients with advanced cancer usually develop a higher symptom burden with disease progression, and have fewerstandard treatment options available.1,2 A small percentage of these patients enroll in phase 1 clinical trials, fueled by thehopes of better disease control and improved survival.3 Although phase 1 agents may result in symptom benefit throughdisease stabilization or shrinkage, they can also be associated with various toxicities and logistical burden, including fre-quent hospital visits and investigations.4,5 These, coupled with cancer-related symptoms and complications, can signifi-cantly compromise a patient’s quality of life.

Phase 1 patients generally have a poor prognosis, with a median survival of 6 to 9 months.6-8 Given the significantmorbidity and mortality reported among phase 1 patients, the involvement of palliative care clinicians can be potentiallybeneficial. Palliative care has evolved as a discipline that focuses on the improvement of the quality of life of cancer patientsand their families through the early identification, assessment, and treatment of symptoms.9 Timely referral to palliativecare is an important indicator of quality of care because patients gain access to multidimensional care early in the trajectory

DOI: 10.1002/cncr.25389, Received: January 29, 2010; Revised: March 11, 2010; Accepted: March 23, 2010, Published online June 2, 2010 in Wiley Online

Library (wileyonlinelibrary.com)

Corresponding author: Eduardo Bruera, MD, Department of Palliative Care and Rehabilitation Medicine, Unit 008, The University of Texas M. D. Anderson Cancer

Center, 1515 Holcombe Boulevard, Houston, TX 77030; Fax: (713) 792-6092; [email protected]

1Department of Palliative Care and Rehabilitation Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; 2Department of Investiga-

tional Cancer Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; 3Department of Biostatistics, The University of Texas M. D.

Anderson Cancer Center, Houston, Texas

We would like to thank Ray Chacko for assistance with database management.

4402 Cancer September 15, 2010

Original Article

of illness.10,11 However, studies have indicated that phase1 patients are less likely to consider palliative care, homehealth aides, counselors, and chaplains.12 Thus, the pur-suit of phase 1 therapy may potentially delay referral topalliative care.

To our knowledge, only 1 study concerning thesymptom burden of phase 1 patients compared with non-phase 1 patients has been published to date,12 and no in-formation regarding the impact of phase 1 involvementon the timing of referral to palliative care is available. Abetter understanding of the timing of palliative care refer-ral and symptom profile can provide the foundation foroptimizing care for these individuals. Using a retrospec-tive cohort design, we compared the timing of referral andsymptom burden between patients referred to palliativecare by phase 1 oncologists and those referred by non-phase 1 oncologists.

MATERIALS AND METHODS

Subjects

The Institutional Review Board at The University ofTexas M. D. Anderson Cancer Center (MDACC)approved the current study and waived the requirementfor informed consent. All patients with advanced solidtumors who were referred to the outpatient supportivecare clinic at MDACC between January 1, 2007 and De-cember 31, 2008 as the first palliative care consultationwere identified. Fifty-seven patients were referred byphase 1 oncologists, and were designated as the phase 1cohort. Among the remaining patients, we randomlyselected 114 as the non-phase 1 cohort, and these patientswere stratified by age (<60 years or �60 years), sex (maleor female), and cancer diagnosis (breast, gastrointestinal,genitourinary, gynecologic, head and neck, lung, andother) in a 1:2 ratio.

Patient Characteristics, Symptoms, andTiming of Referral

We retrospectively retrieved patient demographics (age,sex, and race); cancer diagnosis; timing of diagnosis;encounters with medical oncology, phase 1, and palliativecare; treatment history; and survival from institutionaldatabases, electronic health records, and the TumorRegistry vital statistics database. We also collected infor-mation regarding the Edmonton Symptom AssessmentScale (ESAS), the Memorial Delirium Assessment Scale(MDAS), and the Eastern Cooperative Oncology Group

(ECOG) performance status at the time of palliative careoutpatient consultation.

Statistical Analysis

We summarized the baseline demographics and symptomprofile using descriptive statistics, including medians,means, standard deviations, ranges, and frequencies to-gether with 95% confidence intervals (95%CIs).

We compared the baseline characteristics and symp-tom profile between the phase 1 and non-phase 1 patientcohorts. Comparisons were made using the Student t testfor continuous variables that were normally distributed(ie, ESAS); the Mann-Whitney U test for continuous,nonparametric variables (eg, prior systemic therapycourses); and the chi-square test or Fisher exact test forcategorical variables (eg, MDAS). A 2-sided P value <.05was considered to be statistically significant.

Timing of palliative care referral was defined a prioribased on 2 intervals, including time from registration atMDACC to palliative care consultation and overall sur-vival from the time of palliative care consultation. Alltime-event analyses were plotted using the Kaplan-Meiermethod, and survival curves were compared with the log-rank test.13,14 Overall survival was calculated from thedate of palliative care referral to the date of death fromany cause or the date at which the patient was last knownto be alive. Multivariate analysis was performed using theCox proportional hazards model with backwardelimination.

The Statistical Package for the Social Sciences(SPSS) (version 16.0; SPSS Inc, Chicago, Ill) software wasused for statistical analysis.

RESULTS

Baseline Characteristics

Table 1 summarizes patient demographics at the time ofthe first outpatient palliative care clinic consultation.Patients referred by phase 1 oncologists were less likely topresent with metastatic disease and to have received moreprior chemotherapy regimens compared with thosereferred by non-phase 1 oncologists. Among the phase 1patient cohort, 6 (11%), 13 (23%), 13 (23%), and 25(43%) patients completed 1, 2, 3, and�4 lines of chemo-therapy, respectively, before palliative care consultationcompared with 33 (29%), 25 (22%), 14 (12%), and 19(17%) patients, respectively, in the non-phase 1 group. Asmall percentage (26%) of patients in the phase 1 cohortwere seen directly by phase 1 without medical oncology

Phase 1 and Palliative Care/Hui et al

Cancer September 15, 2010 4403

involvement from our institution. Among the non-phase1 cohort, 12 of 114 (11%) patients had also been seenduring phase 1, but were referred by nononcologists topalliative care.

Symptom Profile

The symptom burden at the time of the first outpatientpalliative care clinic consultation is shown in Table 2.Patients referred by phase 1 oncologists had better ECOGperformance status and were less likely to be delirious(MDAS �8) at the time of presentation. The 2 cohortshad similar physical and psychosocial symptoms asassessed by ESAS, although the phase 1 cohort had betteroverall well-being (mean, 4.5 vs 5.5; P ¼ .03) comparedwith the non-phase 1 cohort.

Medical Oncology and Phase 1 Involvement

Compared with the non-phase 1 cohort, patients referredby phase 1 oncologists had significantly longer survivalfrom the time of diagnosis of advanced cancer (Table 3).Both cohorts were followed by medical oncology for asimilar duration (17 months vs 14 months; P ¼ .36).Patients in the phase 1 cohort were referred to phase 1oncologists at a median of 23 months (95% CI, 11-45months) from the time of diagnosis of advanced cancer,and a median of 6.5 months (95% CI, 4.4-8.6 months)before death.

No difference was found with regard to survivalfrom the referring team’s last visit (median, 28 days vs 41days; P ¼ .84); however, the last medical oncology visitwas found to have happened earlier in the phase 1 cohort

Table 1. Baseline Characteristics at Time of Palliative Care Clinic Consultation

Phase 1 Referrals(N557)

Non-Phase 1Referrals (N5114)

P

Age (SD), y 55 (13) 57 (15) .50

Female 25 (44%) 50 (44%) >.99

Ethnicity .39

Caucasian 40 (70%) 73 (64%)

African American 9 (16%) 18 (16%)

Hispanic 4 (7%) 18 (16%)

Other 4 (7%) 5 (4%)

Cancer diagnosis >.99

Breast 5 (9%) 10 (9%)

Gastrointestinal 27 (47%) 54 (47%)

Genitourinary 6 (11%) 12 (11%)

Gynecologic 3 (5%) 6 (5%)

Head and neck 3 (5%) 6 (5%)

Lung 1 (2%) 2 (2%)

Other 12 (21%) 24 (21%)

Stage .046

Recurrent 0 (0%) 3 (3%)

Locally advanced 2 (4%) 16 (14%)

Metastatic 55 (97%) 95 (83%)

No. of lines of chemotherapy regimens prior

to palliative care consultationa3 (2-5) 2 (1-3) <.001

Treated with phase 1 therapy 43 (75%) 4 (4%) <.001

Sequence of team involvementb <.001

Oncology, phase 1, palliative care 42 (74%) 2 (2%)

Phase 1, palliative care 15 (26%) 0 (0%)

Oncology, palliative care 0 (0%) 98 (86%)

Oncology, palliative care, phase 1 0 (0%) 10 (9%)

Palliative care, oncology 0 (0%) 4 (4%)

Median interval from diagnosis of advanced cancer

to palliative care consultation (95% CI), mo

28 (19-37) 12 (9-14) <.001

Deaths 49 (86%) 89 (78%) .22

SD indicates standard deviation; 95% CI, 95% confidence interval.a Between the time of advanced cancer diagnosis and palliative care consultation.bDenotes the time sequence of patient encounters with oncology, phase 1, and palliative care, ordered by the date of

first visit to each service.

Original Article


(200 days vs 41 days; P < .001), suggesting that phase 1oncologists, rather than the referring oncologists, wereprimarily responsible for the care of these patients in theirlast few months of life.

Quality of End-of-Life Care

Among all the patients who died, those referred by phase1 oncologists were more likely than the non-phase 1cohort to have received chemotherapy within the last 30days of life (31% vs 13%; P¼ .014). The interval betweenlast chemotherapy and death also appeared to be shorterfor the phase 1 cohort (median, 60 days vs 81 days; P ¼.06), although this did not achieve statistical significance.

Only a small percentage of patients in both cohortswere admitted to the intensive care unit within the last 30days of life (4% vs 6%; P >.99). We did not detect anydifferences in the percentage of in-hospital deaths betweenthe 2 groups (18% vs 28%; P¼ .21).

Palliative Care Referral

Patients referred by phase 1 oncologists were found tohave a significantly longer interval from the time of diag-nosis of advanced cancer to palliative care consultation, aswell as a longer interval between first oncology contactand palliative care consultation (Table 3). However, the 2key markers of timing of palliative care referral (time fromMDACC registration to palliative care consultation andoverall survival from time of palliative care consultation)did not differ significantly between the 2 groups (Table3). On Cox regression multivariate analysis, only cancerdiagnosis was found to be significantly associated with thetiming of palliative care referral (Table 4).

The duration between the referring team’s initialcontact with the patient and palliative care referral wasshorter for patients in the phase 1 cohort, suggesting thatthese patients were referred promptly to palliative care(Table 3). No difference was found with regard to the du-ration of overlap between palliative care consultation andthe referring team’s last visit (median, 63 days vs 44 days;P¼ .84) (Fig. 1).

Consistent with these findings, the number of medi-cal oncology clinic visits before palliative care consultationand the number of palliative care clinic visits until deathwere found to be similar between the 2 cohorts (Table 3).Patients in the phase 1 cohort had a median of 4 phase 1visits (interquartile range, 1.5-10.5 visits) before a pallia-tive care consultation.

Table 2. Symptom Burden at Time of Palliative Care ClinicConsultation

Symptom Phase 1Referrals(N557)

Non-Phase 1Referrals(N5114)

P

Mean Edmonton Symptom Assessment Scale (SD)Pain 5.3 (2.8) 5.1 (3.0) .70

Fatigue 5.7 (2.6) 6.4 (2.6) .09

Nausea 2.7 (3.2) 2.4 (2.8) .48

Depression 2.6 (3.0) 3.5 (2.9) .07

Anxiety 2.8 (3.0) 3.5 (2.9) .17

Drowsiness 3.7 (3.2) 4.3 (3.2) .27

Appetite 5.0 (3.2) 5.7 (3.3) .21

Well-being 4.5 (2.4) 5.5 (2.8) .03

Dyspnea 3.4 (3.2) 3.1 (2.9) .52

Sleep 4.8 (2.6) 4.6 (3.2) .71

ECOG performance status0-1 35 (61%) 41 (36%) .003

2-3 19 (33%) 68 (60%)

4 3 (5%) 5 (4%)

Delirium (MDAS �8) 0 (0%) 10 (9%) .032

SD indicates standard deviation; ECOG, Eastern Cooperative Oncology

Group; MDAS, Memorial Delirium Assessment Scale.

Table 3. Timing of Palliative Care and Phase 1 Referrals

Phase 1Referrals (N557)

Non-Phase 1Referrals (N5114)

P

Median interval (95% CI), moDiagnosis of advanced cancer to death 36 (25-47) 23 (17-29) .01

Diagnosis of advanced cancer to palliative care consultation 28 (19-37) 12 (9-14) <.001

MDACC registration to palliative care consultation 13 (8-20) 11 (5-15) .41

Palliative care consultation to death 5 (3-6) 4 (3-5) .69

First medical oncology contact to palliative care consultation 19 (13-25) 8 (4-12) .019

First referring team contact to palliative care consultation 1 (0.6-1.5) 9 (5-13) <.001

Median no. of clinic visits (IQR)Medical oncology visits before palliative care consultation 12.5 (4.8-24) 10 (4.5-21.5) .45

Palliative care visits until last follow-up/death 4 (3-7) 4 (2-6) .39

95% CI indicates 95% confidence interval; MDACC, The University of Texas M. D. Anderson Cancer Center; IQR, interquartile range.



DISCUSSIONIn this retrospective cohort study, we found that patientsreferred to palliative care by phase 1 oncologists had a bet-ter ECOG performance status but similar symptom bur-den compared with those referred by non-phase 1oncologists, and were more likely to receive chemotherapyclose to the end of their life. Survival from the time of pal-liative care referral was approximately 4 months for bothcohorts, suggesting that phase 1 involvement did notdelay palliative care referral. This supports the develop-ment of a successful simultaneous care model.

One interesting, although not completely surpris-ing, finding from the current study was that the phase 1cohort had a longer overall survival from the time of diag-nosis of advanced cancer compared with the non-phase 1cohort, suggesting that these patients generally had a lessaggressive disease course compared with patients whowere not referred.15 In contrast, several patients in thenon-phase 1 cohort deteriorated rapidly, thereby limitingtheir ability to enroll in clinical trials.

We found that patients from the phase 1 cohorthad a better ECOG performance status and were lesslikely to be delirious at the time of presentation to palli-ative care; this finding is not surprising given thatpatients need to be well enough to be referred for phase1 treatments.15,16 We found that phase 1 patients other-wise had similar symptom expression compared with

non-phase 1 patients. These findings are consistent witha recent prospective cohort study from a different insti-tution using the Memorial Symptom AssessmentScale.12 Similar to other studies regarding palliative carepopulations, fatigue, pain, and anorexia were found tobe the most common and severe symptoms in bothcohorts.17 Importantly, our results support that bothphase 1 and non-phase 1 patients have significant physi-cal and psychological distress at the time of presentationto the outpatient palliative care clinic, indicating theneed for intensive interventions.

Table 4. Cox Regression Multivariate Analysis of Survivalfrom Palliative Care Consultationa

HR (95% CI) P

Cancer diagnosis .05

Breast 0.52 (0.26-1.06) .07

Gastrointestinal 1.0 Reference

Genitourinary 0.87 (0.48-1.59) .65

Gynecologic 0.94 (0.43-2.06) .88

Head and neck 0.66 (0.31-1.39) .27

Lung 0.60 (0.15-2.47) .48

Othersb 0.43 (0.26-0.71) .001

ECOG performance status 1.17 (0.98-1.40) .09

HR indicates hazard ratio; 95% CI, 95% confidence interval; ECOG, East-

ern Cooperative Oncology Group.a Variables included in this model were age, sex, race, cancer diagnosis,

stage, referring team, ECOG performance status at presentation, number of

medical oncology visits before palliative care consultation, and number of

chemotherapy courses before palliative care consultation. Because this

model aimed to identify factors that affect the timing of referral rather than

factors that confer a poor prognosis, we specifically excluded symptoms

from the analysis because some are known to be prognostic factors (eg,

delirium and dyspnea) that could potentially confound this analysis.b Included all cancer types other than breast, gastrointestinal, genitourinary,

gynecologic, and head and neck cancers. Examples included sarcoma as

well as neurologic and endocrine tumors.

Figure 1. Timing of palliative care referral is shown as Kaplan-Meir curves for (A) the interval between registration at TheUniversity of Texas M. D. Anderson Cancer Center and pallia-tive care consultation and (B) the interval between palliativecare consultation and death.

Original Article


We had several reasons to suspect that phase 1patients could be referred to palliative care later than non-phase 1 patients. Phase 1 treatments are typically offeredlate in the disease trajectory, when patients have alreadyexhausted all standard treatments. Thus, although thenon-phase 1 oncologists have ample opportunities tomake palliative care referrals early in the disease course,the timing of referral by phase 1 physicians depends onwhen the phase 1 consultations take place, which are gen-erally within the last few months of life.

In addition to logistical challenges, the literaturesuggests that patients taking part in phase 1 trials are notpsychologically prepared for the transition to end-of-lifecare.12,18 Agrawal et al surveyed 163 patients on phase 1protocols regarding their decision-making process.Although>80% of patients stated that they were aware ofpalliative care and hospice as alternatives to phase 1 trials,fewer than 10% seriously considered these options forthemselves.18 Potential explanations include a lack ofunderstanding of palliative care services, lack of a self-per-ceived need for support services because of better perform-ance status, and the desire to focus only on cancertreatments. Indeed, patients embarking on phase 1 trialsgenerally have heightened expectations with regard to sur-vival and treatment outcomes.19,20 This, coupled with asense of denial, makes them much less likely to desire pal-liative care services. Finally, the misconception by someoncologists that a palliative care referral could destroyhope presents another barrier to the referral process.21,22

Despite the many factors that could potentially limitpalliative care referral among phase 1 patients, we wereencouraged to find that phase 1 involvement did notappear to delay palliative care referral. In the currentstudy, the median duration between first phase 1 contactand palliative care referral was only 31 days, suggestingthat phase 1 physicians made their referral relativelyquickly, without significant delays. Because phase 1 physi-cians work closely with patients with advanced cancernear the end of life, they may have a better understandingof the palliative care needs of their patients, and the poten-tial benefits related to a timely referral. For individuals toosick to enroll on an experimental protocol, they may bereferred to palliative care for transition to end-of-life care.For other patients participating in phase 1 trials, palliativecare helps to support them through treatment by optimiz-ing their functional status, symptoms, and supportsystems.

Consistent with this model of integrated care,patients referred by phase 1 oncologists were more likely

to receive chemotherapy within the last 30 days of life.This finding is not unexpected given that these patientswere actively seeking further treatments. The administra-tion of chemotherapy close to the end of life has been usedas an indicator of poor quality of cancer care.23-25 How-ever, this marker is of limited value as an outcome mea-sure because the timing of death cannot be accuratelypredicted. There are always patients who desire aggressivetreatments despite understanding the unfavorable risk:be-nefit ratio. Finally, the emergence of targeted therapieswith a lower toxicity profile compared with traditional cy-totoxic therapies has allowed sicker patients to receiveanticancer treatments later in the disease trajectory. Thus,the 30-day criterion may not be appropriate for phase 1cancer patients.

Close collaborations between phase 1 and pallia-tive care physicians under a simultaneous care modelcan help optimize both quantity and quality of life,while tailoring care to the individual’s needs.26-28 Clini-cians, patients, and families should understand that theydo not have to choose between phase 1 and palliativecare, but could take advantage of both services synergis-tically. Under this integrated care approach, phase 1oncologists can deliver the latest cancer treatments withthe aim of cancer control, while the palliative care teamfocuses on symptom management, psychosocial inter-ventions, family counseling, and transition of care.Given the significant symptom burden, emotional dis-tress, and poor prognosis of phase 1 patients, nearly allof them may benefit from this simultaneous careapproach.

To the best of our knowledge, the optimal timingfor palliative care referral has not been defined to date,although the general understanding is that patients arereferred late.29-31 The American Society of Clinical On-cology recently published a position statement supportingthe vision of integrating palliative care into oncology prac-tice from the time of cancer diagnosis.11 In our study ofpatients who were first referred as outpatients, palliativecare involvement was limited to the last 4 months of life,with a median of 4 clinical encounters. Thus, much workremains to be done to provide palliative care earlier in thedisease trajectory, ideally before the phase 1 oncologistvisit. Studies from our group and others have demon-strated that palliative care referral is dependent on variousfactors, including the oncologist’s perception and atti-tudes,21,32 patient characteristics and preferences,33,34

and healthcare infrastructure and policies.35 Consistentwith the literature,36 we found that a cancer diagnosis,



which dictates which team of oncologists the patient sees,is a key determinant regarding the timing of referral topalliative care. Although not examined in the currentstudy, factors associated with referral to phase 1 oncolo-gists may include institutional resources, the oncologist’sattitudes, and patient education and preferences, as well ascancer site and stage of disease.15,37,38

The current study has several limitations. First,data were collected retrospectively. Second, although ourphase 1 and palliative care programs represent some ofthe largest programs in the United States, the sample sizewas small. This is partly because we elected to focus onoutpatient referrals as a model of integration. Third, thecurrent study only examined the timing of referralbecause we did not have access to the data of patientswho, although seen by phase 1 and non-phase 1 oncolo-gists, were not subsequently referred to palliative care.Fourth, approximately 11% of patients in the non-phase1 cohort had consulted phase 1 oncologists either beforeor after palliative care consultation, although they werenot referred by the phase 1 oncologist. This ‘‘contamina-tion’’ may have reduced any observed differences in ouroutcomes. Finally, findings from the current study areinstitution-specific and are not generalizable to otherprograms. Nevertheless, it demonstrates how 2 health-care teams with seemingly opposing objectives can carefor patients collaboratively.

To our knowledge, this is the first study to examinethe timing of referral to palliative care between patientstreated by phase 1 and non-phase 1 oncologists. Wefound that phase 1 involvement did not delay palliativecare referral in our institution. Despite having a betterECOG performance status, patients referred by phase 1oncologists were found to have a significant symptomburden similar to that of patients referred by non-phase1 services, and were more likely to be receiving chemo-therapy closer to the time of death. These findings indi-cate the need for interdisciplinary palliative careinterventions concurrent with phase 1 under a simultane-ous care model. Although not every patient requires in-tensive symptom management up front, timely referralcan facilitate rapport building, longitudinal psychosocialsupport, early recognition and treatment of symptoms,and advance care planning. To ensure timely access tocomprehensive cancer care for all patients, improvementsin reimbursement policy; palliative care resources; andthe education of oncologists, patients, and families aswell as research examining novel integration models areurgently needed.

CONFLICT OF INTEREST DISCLOSURESSupported in part by National Institutes of Health grantsRO1NR010162-01A1, RO1CA122292-01, and RO1CA124481-01 (to Dr. Bruera); and the Clinician InvestigatorProgram, Royal College of Physicians and Surgeons of Canada(to Dr. Hui).

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timing of palliative care referral and symptom burden in phase 1 cancer patients : a retrospective...

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