Phase 1 cancer clinical trials offer potential disease modifying treatments for patients with advanced cancer who have not responded to standard treatments. These patients also experience palliative care needs that should be addressed. However, misunderstandings may arise between the goals of experimental treatments and the goals of palliative care, especially when the latter focuses on quality of life.
Aim:
This study aimed to map the existing literature on the provision and integration of palliative care within phase 1 clinical trials, identifying knowledge gaps and informing future research.
Design:
A systematic scoping review.
Data sources:
Studies published from 2003 to 2023 were identified through searches in PubMed, Web of Science, Scopus, CINAHL, PsycINFO and Google Scholar, focussing on people living with advanced cancer enrolled in phase 1 clinical trials.
Results:
Fifty studies were included from 452 screened. Key results revealed patients’ limited life expectancy, high symptom burden, distress and unmet spiritual needs. Notably, patients were reluctant to seek prognostic information or engage in end-of-life discussions, complicating advance care planning. End-of-life care involved frequent unscheduled hospital admissions, hospital deaths and late hospice-care referrals. Caregivers experienced significant distress, while healthcare professionals faced barriers to integrating palliative care. Palliative care interventions varied widely in approaches, settings and outcomes.
Conclusion:
This review highlights the unique needs of patients and caregivers in Phase 1 Cancer Clinical Trials and the complexities of integrating palliative care. Future research should focus on integrating specialised palliative care into oncology trials and developing standardised guidelines for clinical trial units.
SandersJJTeminSGhoshalA, et al. Palliative care for patients with cancer: ASCO guideline update. J Clin Oncol2024; 42: 2336–2357.
2.
LinAGiulianoCJPalladinoA, et al. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci Transl Med2019; 11(509): eaaw8412.
3.
PaolettiXLe TourneauCVerweijJ, et al. Defining dose-limiting toxicity for phase 1 trials of molecularly targeted agents: results of a DLT-TARGETT international survey. Eur J Cancer2014; 50: 2050–2056.
4.
YuzhalinAE. Redefining cancer research for therapeutic breakthroughs. Br J Cancer2024; 130: 1078–1082.
5.
ArkenauHTBarriusoJOlmosD, et al. Prospective validation of a prognostic score to improve patient selection for oncology phase 1 trials. J Clin Oncol2009; 27: 2692–2696.
6.
BigotFCastanonEBaldiniC, et al. Prospective validation of a prognostic score for patients in immunotherapy phase I trials: the Gustave Roussy Immune Score (GRIm-Score). Eur J Cancer2017; 84: 212–218.
7.
ArkenauHTOlmosDAngJE, et al. Clinical outcome and prognostic factors for patients treated within the context of a phase I study: the Royal Marsden Hospital experience. Br J Cancer2008; 98: 1029–1033.
8.
BiessenDAJCranendonkMASchiavonG, et al. Evaluation of patient enrollment in Oncology Phase I Clinical Trials. Oncologist2013; 18: 323–329.
9.
MurthyVHKrumholzHMGrossCP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA2004; 291: 2720–2726.
10.
KaravasilisVDigueLArkenauT, et al. Identification of factors limiting patient recruitment into phase I trials: a study from the Royal Marsden Hospital. Eur J Cancer2008; 44: 978–982.
11.
BellhouseSGalvinLTurnerL, et al. Phase I cancer trials: a qualitative study of specialist palliative care. BMJ Support Palliat Care2020; 10: 234–241.
12.
KapoJCasarettD. Palliative care in phase 1 trials: an ethical obligation or undue inducement?J Palliat Med2002; 5(5): 661–665.
13.
ComorettoNLarumbeAArantzamendiM, et al. Palliative care consultants’ ethical concerns with advanced cancer patients participating in phase 1 clinical trials: a case study. Prog Palliat Care2017; 25: 230–234.
14.
FerrellBChungVHughesMT, et al. A palliative care intervention for patients on phase 1 studies. J Palliat Med2021; 24: 846–856.
15.
JenkinsVSolis-TrapalaILangridgeC, et al. What oncologists believe they said and what patients believe they heard: an analysis of phase I trial discussions. J Clin Oncol2011; 29: 61–68.
16.
AgrawalMGradyCFaircloughDL, et al. Patients’ decision-making process regarding participation in phase I oncology research. J Clin Oncol2006; 24: 4479–4484.
17.
ZafarSYCurrowDCChernyN, et al. Consensus-based standards for best supportive care in clinical trials in advanced cancer. Lancet Oncol2012; 13: e77–e82.
18.
HuiDMoriMWatanabeSM, et al. Referral criteria for outpatient specialty palliative cancer care: an international consensus. Lancet Oncol2016; 17: e552–e559.
19.
HuiDChernyNIWuJ, et al. Indicators of integration at ESMO designated centres of integrated oncology and palliative care. ESMO Open2018; 3: e000372.
20.
PetersMDGodfreyCMKhalilH, et al. Guidance for conducting systematic scoping reviews. Int J Evid Based Healthc2015; 13: 141–146.
21.
Sanz RubialesÁSánchez-GutiérrezMEFlores PérezLA, et al. How is best supportive care provided in clinical trials for patients with advanced cancer? A review of registered protocols of clinical trials. Curr Oncol2020; 27: 100–105.
22.
LeeRTRamchandranKSanftT, et al. Implementation of supportive care and best supportive care interventions in clinical trials enrolling patients with cancer. Ann Oncol2015; 26: 1838–1845.
23.
Goni-FusteBPergolizziDMonforte-RoyoC, et al. Development of a guide to multidimensional needs assessment in the palliative care initial encounter (MAP). J Pain Symptom Manag2023; 66: 361–369.e6.
24.
AnwarSTanWHongCC, et al. Quality-of-Life (QOL) during screening for phase 1 trial studies in patients with advanced solid tumors and its impact on risk for serious adverse events. Cancers2017; 9: 1–12.
25.
CarrALBilendukeEAdolfE, et al. A pilot randomized study of a telephone-based cognitive-behavioral stress-management intervention to reduce distress in phase 1 oncology trial caregivers. Palliat Support Care2023; 21: 820–828.
26.
CasselJBDel FabbroEArkenauT, et al. Phase I cancer trials and palliative care: antagonism, irrelevance, or synergy?J Pain Symptom Manag2016; 52: 437–445.
27.
ChungVSunVRuelN, et al. Improving palliative care and quality of life in pancreatic cancer patients. J Palliat Med2022; 25: 720–727.
28.
EnzingerACZhangBWeeksJC, et al. Clinical trial participation as part of end-of-life cancer care: associations with medical care and quality of life near death. J Pain Symptom Manag2014; 47: 1078–1090.
29.
AthertonPJSzydloDWErlichmanC. What can phase I clinical trials tell us about quality of life? A pilot study (MC0115). Clin Res Trials2015; 1: 11–14.
30.
FerrellBRPatersonCLHughesMT, et al. Characteristics of participants enrolled onto a randomized controlled trial of palliative care for patients on phase I studies. J Palliat Med2017; 20: 1338–1344.
31.
FerrellBRChungVKoczywasM, et al. Palliative care and phase 1 trials. Clin J Oncol Nurs2017; 21: 473–479.
32.
FerrellBWilliamsACBornemanT, et al. Clinical trials understanding patient perspectives and beliefs about treatment. Clin J Oncol Nurs2019; 23: 592–598.
33.
FerrellBBornemanTWilliamsAC, et al. Integrating palliative care for patients on clinical trials: opportunities for oncology nurses. Asia Pac J Oncol Nurs2020; 7: 243–249.
34.
FuSBarberFDNaingA, et al. Advance care planning in patients with cancer referred to a phase I clinical trials program: the MD Anderson Cancer Center experience. J Clin Oncol2012; 30: 2891–2896.
35.
HuiDParsonsHNguyenL, et al. Timing of palliative care referral and symptom burden in phase 1 cancer patients: a retrospective cohort study. Cancer2010; 116: 4402–4409.
36.
KinahanHMaitiAHessK, et al. Post-discharge survival outcomes of patients with advanced cancer from the University of Texas MD Anderson Cancer Center investigational cancer therapeutics (phase I trials) inpatient unit. Oncology2017; 92: 14–20.
37.
HealyJMPatelTLeeS, et al. Do symptoms matter when considering patients for phase I clinical trials? A pilot study of older adults with advanced cancer. Am J Hosp Palliat Med2011; 28: 463–466.
38.
MeyersFJLinderJBeckettL, et al. Simultaneous care: a model approach to the perceived conflict between investigational therapy and palliative care. J Pain Symptom Manag2004; 28: 548–556.
39.
MeyersFJCarducciMLoscalzoMJ, et al. Effects of a problem-solving intervention (COPE) on quality of life for patients with advanced cancer on clinical trials and their caregivers: Simultaneous Care Educational Intervention (SCEI): linking palliation and clinical trials. J Palliat Med2011; 14: 465–473.
40.
FinlayELuHLHendersonHR, et al. Do phase 1 patients have greater needs for palliative care compared with other cancer patients?Cancer2009; 115: 446–453.
41.
FerrellBChungVKoczywasM, et al. Spirituality in cancer patients on phase 1 clinical trials. Psychooncology2020; 29: 1077–1083.
42.
JansenLAMahadevanDAppelbaumPS, et al. Perceptions of control and unrealistic optimism in early-phase cancer trials. J Med Ethics2018; 44: 121–127.
43.
KesslerERMossAEckhardtSG, et al. Distress among caregivers of phase I trial participants: a cross-sectional study. Support Care Cancer2014; 22: 3331–3340.
44.
KvaleEAWoodbyLWilliamsBR. The experience of older patients with cancer in phase 1 clinical trials: a qualitative case series. Am J Hosp Palliat Care2010; 27: 474–481.
45.
MollicaMAKentEECastroKM, et al. Perspectives on palliative care in cancer clinical trials: diverse meanings from multidisciplinary cancer care providers. J Palliat Med2018; 21: 616–621.
46.
NippRDLeeHGortonE, et al. Addressing the financial burden of cancer clinical trial participation: longitudinal effects of an equity intervention. Oncologist2019; 24: 1048–1055.
47.
ParsonsHABaracosVEDhillonN, et al. Body composition, symptoms, and survival in advanced cancer patients referred to a phase I service. PLoS One2012; 7: e29330.
48.
RezashVReedJGedeonB, et al. Who needs what? Perceptions of patients and caregivers in oncology phase 1 trials. J Patient Exp2020; 7: 27–33.
49.
RoweJPatelSMazo-CanolaM, et al. An evaluation of elderly patients (⩾70years old) enrolled in phase I clinical trials at University of Texas Health Science Center at San Antonio-Cancer Therapy Research Center from 2009 to 2011. J Geriatr Oncol2014; 5: 65–70.
50.
SaikiCFerrellBLongo-SchoeberleinD, et al. Goals-of-care discussions. J Community Support Oncol2017; 15: e190–e194.
51.
SedhomRFerrellBRuelN, et al. Using patient-reported outcomes to describe the patient experience on phase I clinical trials. JNCI Cancer Spectr2020; 4: 1–11.
52.
SedhomRBlackfordALGuptaA, et al. End-of-life characteristics associated with short hospice length of stay for patients with solid tumors enrolled in phase I clinical trials. J Natl Compr Canc Netw2021; 19: 686–692.
53.
SunVCookeLChungV, et al. Feasibility of a palliative care intervention for cancer patients in phase I clinical trials. J Palliat Med2014; 17: 1365–1368.
54.
TreasureMDalyBCaoS, et al. A randomized controlled trial of structured palliative care versus standard supportive care for patients enrolled in phase 1 clinical trials. Cancer Med2021; 10: 4312–4321.
55.
TreasureMDalyBFuP, et al. Relationship between phase I study duration and symptom burden. Support Care Cancer2018; 26: 731–737.
56.
WhelerJTsimberidouAMHongD, et al. Survival of patients in a phase 1 clinic: the M. D. Anderson Cancer Center experience. Cancer2009; 115: 1091–1099.
57.
BellJABalneavesLG. Cancer patient decision making related to clinical trial participation: an integrative review with implications for patients’ relational autonomy. Support Care Cancer2015; 23: 1169–1196.
58.
KoganNTolleyMCohenR. Family caregivers support their patient’s decision to participate in a phase 1 clinical trial: weighing the pros and cons, bearing the costs. Psychooncology2022; 31: 1374–1380.
59.
van LentLGGJabbarianLJvan GurpJ, et al. Identifying patient values impacting the decision whether to participate in early phase clinical cancer trials: a systematic review. Cancer Treat Rev2021; 98: 102217.
60.
Van Sasse Van IJsseltMEAVan der BiessenDAJVan PuffelenAJ, et al. “If only I had”, patients’ experiences during early oncology trials. Support Care Cancer2023; 31(5): 290.
61.
van der BiessenDAvan der HelmPGKleinD, et al. Understanding how coping strategies and quality of life maintain hope in patients deliberating phase I trial participation. Psychooncology2018; 27: 163–170.
62.
van LentLGGStoelNKvan WeertJCM, et al. Realizing better doctor-patient dialogue about choices in palliative care and early phase clinical trial participation: towards an online value clarification tool (OnVaCT). BMC Palliat Care2019; 18: 106.
63.
EscrittKMannMNelsonA, et al. Hope and meaning-making in phase 1 oncology trials: a systematic review and thematic synthesis of qualitative evidence on patient-participant experiences. Trials2022; 23: 409.
64.
MoorcraftSYMarriottCPeckittC, et al. Patients’ willingness to participate in clinical trials and their views on aspects of cancer research: results of a prospective patient survey. Trials2016; 17: 17.
65.
HilmiMNaounNBoilèveA, et al. Evaluation of supportive care needs, sexuality and quality of life in phase 1 trials: a prospective monocentric study. Support Care Cancer2022; 30: 9841–9849.
66.
RouanneMMassardCHollebecqueA, et al. Evaluation of sexuality, health-related quality-of-life and depression in advanced cancer patients: a prospective study in a phase I clinical trial unit of predominantly targeted anticancer drugs. Eur J Cancer2013; 49: 431–438.
67.
NielsenZEBerthelsenCB. Cancer patients’ perceptions of factors influencing their decisions on participation in clinical drug trials: a qualitative meta-synthesis. J Clin Nurs2019; 28: 2443–2461.
68.
ViljoenBChambersSKDunnJ, et al. Deciding to enrol in a cancer trial: a systematic review of qualitative studies. J Multidiscip Healthc2020; 13: 1257–1281.
69.
YangGMOngWYTanJ, et al. Motivations and experiences of patients with advanced cancer participating in phase 1 clinical trials: a qualitative study. Palliat Med2023; 37: 257–264.
70.
AgrawalMEmanuelEJ. Ethics of Phase 1 Oncology studies: reexamining the arguments and data. JAMA2003; 290: 1075–1082.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
