A randomized controlled trial of structured palliative care versus standard supportive care for patients enrolled in phase 1 clinical trials

Michelle Treasure, Barbara Daly, Shufen Cao, Pingfu Fu, Augustine Hong, Elizabeth Weinstein, Jessica Surdam, Neal J Meropol, Afshin Dowlati, Michelle Treasure, Barbara Daly, Shufen Cao, Pingfu Fu, Augustine Hong, Elizabeth Weinstein, Jessica Surdam, Neal J Meropol, Afshin Dowlati

Abstract

Purpose: Patients enrolled in Phase 1 clinical trials have typically exhausted standard therapies and often are choosing between a clinical trial and hospice care. Significant symptom burden can result in early trial discontinuation and confound trial outcomes. This study aimed to examine differences in study duration, symptom burden, adverse events (AE), and quality of life (QOL) between those receiving structured palliative care versus usual supportive care.

Patients and methods: Sixty-eight patients enrolled in phase 1 clinical trials and 39 of their CGs were randomly assigned to receive structured palliative care or usual supportive care. Patient QOL was measured monthly using the Functional Assessment of Cancer Therapy and Memorial Symptom Assessment Scale. The Quality of Life in Life-Threatening Illness-Family Care Version and Caregiver Reaction Assessment were used for CGs. AEs and use of palliative care resources were compared between arms.

Results: Mean duration of the phase 1 study was 142 days in the palliative care arm versus 116 days in the usual care arm (p = 0.55). Although not statistically significant, patients in the palliative care arm experienced fewer AEs and better QOL, as did their CGs, compared to those receiving usual care.

Conclusions: Phase 1 patients and their CGs have physical and psychosocial needs warranting palliative care services. Results suggest that structured palliative care is associated with the increased duration of the study and improved patient and CG QOL.

Trial registration: ClinicalTrials.gov NCT02543541.

Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form. Only Neal Meropol reported disclosure of others from Flatiron Health and Roche.

© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Patient consort diagram
FIGURE 2
FIGURE 2
Change of symptom burden and quality of life over time (90 days) in patients and caregivers
FIGURE 3
FIGURE 3
Comparison of adverse event rates (weighted and unweighted per month)
FIGURE 4
FIGURE 4
Caregiver consort diagram

References

    1. Cheng JD, Hitt J, Koczwara B, et al. Impact of quality of life on patient expectations regarding phase I clinical trials. J Clin Oncol. 2000;18(2):421‐428. 10.1200/JCO.2000.18.2.421.
    1. Horstmann E, McCabe MS, Grochow L, et al. Risks and benefits of phase 1 oncology trials, 1991 through 2002. N Engl J Med. 2005;352(9):895‐904. 10.1056/NEJMsa042220.
    1. Chakiba C, Grellety T, Bellera C, Italiano A. Encouraging trends in modern phase 1 oncology trials. N Engl J Med. 2018;378(23):2242‐2243. 10.1056/NEJMc1803837.
    1. Finlay E, Lu HL, Henderson H, O’Dwyer PJ, Casarett DJ. Do phase 1 patients have greater needs for palliative care compared with other cancer patients? Cancer. 2009;115(2):446‐453. 10.1002/cncr.24025.
    1. Healy JM, Patel T, Lee S, Sanchez‐Reilly S. Do symptoms matter when considering patients for phase I clinical trials?: a pilot study of older adults with advanced cancer. Am J Hosp Palliat Care. 2011;28(7):463‐466. 10.1177/1049909111400723.
    1. Hyman DM, Eaton AA, Gounder MM, et al. Nomogram to predict cycle‐one serious drug‐related toxicity in phase I oncology trials. J Clin Oncol. 2014;32(6):519‐526. 10.1200/JCO.2013.49.8808.
    1. Treasure M, Daly B, Fu P, Kerpedjieva S, Dowlati A, Meropol NJ. Relationship between phase I study duration and symptom burden. Support Care Cancer. 2018;26(3):731‐737. 10.1007/s00520-017-3879-1.
    1. Martinez KA, Snyder CF, Malin JL, Dy SM. Is race/ethnicity related to the presence or severity of pain in colorectal and lung cancer? J Pain Symptom Manage. 2014;48(6):1050‐1059. 10.1016/j.jpainsymman.2014.02.005.
    1. Kroenke K, Zhong X, Theobald D, Wu J, Tu W, Carpenter JS. Somatic symptoms in patients with cancer experiencing pain or depression: prevalence, disability, and health care use. Arch Intern Med. 2010;170(18):1686‐1694. 10.1001/archinternmed.2010.337.
    1. Berry LL, Dalwadi SM, Jacobson JO. Supporting the supporters: what family caregivers need to care for a loved one with cancer. J Oncol Pract. 2017;13(1):35‐41. 10.1200/JOP.2016.017913.
    1. Yabroff KR, Kim Y. Time costs associated with informal caregiving for cancer survivors. Cancer. 2009;115(18 Suppl):4362‐4373. 10.1002/cncr.24588.
    1. Northouse L, Williams A‐L, Given B, McCorkle R. Psychosocial care for family caregivers of patients with cancer. J Clin Oncol. 2012;30(11):1227‐1234. 10.1200/JCO.2011.39.5798.
    1. Rocque GB, Cleary JF. Palliative care reduces morbidity and mortality in cancer. Nat Rev Clin Oncol. 2013;10(2):80‐89. 10.1038/nrclinonc.2012.211.
    1. Ferrell B, Wittenberg E. A review of family caregiving intervention trials in oncology. CA Cancer J Clin. 2017;67(4):318‐325. 10.3322/caac.21396.
    1. Ferrell BR, Temel JS, Temin S, et al. Integration of palliative care into standard oncology care: American society of clinical oncology clinical practice guideline update. J Clin Oncol. 2017;35(1):96‐112. 10.1200/JCO.2016.70.1474.
    1. Rubinstein LV, Korn EL, Freidlin B, Hunsberger S, Percy Ivy S, Smith MA. Design issues of randomized phase II trials and a proposal for phase II screening trials. J Clin Oncol. 2005;23(28):7199‐7206. 10.1200/JCO.2005.01.149.
    1. Hui D, Parsons H, Nguyen L, et al. Timing of palliative care referral and symptom burden in phase 1 cancer patients: a retrospective cohort study. Cancer. 2010;116(18):4402‐4409. 10.1002/cncr.25389.
    1. Ferrell BR, Chung V, Koczywas M, et al. Palliative care and phase 1 trials: Intervention to improve quality of life and provide education. Clin J Oncol Nurs. 2017;21(4):473‐479. 10.1188/17.CJON.473-479.
    1. Cassel JB, Del Fabbro E, Arkenau T, et al. Phase I cancer trials and palliative care: antagonism, irrelevance, or synergy? J Pain Symptom Manage. 2016;52(3):437‐445. 10.1016/j.jpainsymman.2016.02.014.
    1. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non‐small‐cell lung cancer. N Engl J Med. 2010;363(8):733‐742. 10.1056/NEJMoa1000678.
    1. Ferrell BR, Paterson CL, Hughes MT, Chung V, Koczywas M, Smith TJ. Characteristics of participants enrolled onto a randomized controlled trial of palliative care for patients on phase I studies. J Palliat Med. 2017;20(12):1338‐1344. 10.1089/jpm.2017.0158.
    1. Kluetz PG, Chingos DT, Basch EM, Mitchell SA. Patient‐reported outcomes in cancer clinical trials: measuring symptomatic adverse events with the National Cancer Institute’s patient‐reported outcomes version of the common terminology criteria for adverse events (PRO‐CTCAE). Am Soc Clin Oncol Educ B. 2016;36:67‐73. 10.1200/edbk_159514.
    1. Basch E, Deal AM, Dueck AC, et al. Overall survival results of a trial assessing patient‐reported outcomes for symptom monitoring during routine cancer treatment. JAMA ‐ J Am Med Assoc. 2017;318(2):197‐198. 10.1001/jama.2017.7156.
    1. Smith TJ, Chung V, Hughes MT, et al. A randomized trial of a palliative care intervention for patients on phase I studies. J Clin Oncol. 2020;38(15_suppl):12001. 10.1200/jco.2020.38.15_suppl.12001.
    1. Given B, Wyatt G, Given C, et al. Burden and depression among caregivers of patients with cancer at the end of life. Oncol Nurs Forum. 2004;31(6):1105‐1117. 10.1188/04.ONF.1105-1117.
    1. Hui D, Kim SH, Roquemore J, Dev R, Chisholm G, Bruera E. Impact of timing and setting of palliative care referral on quality of end‐of‐life care in cancer patients. Cancer. 2014;120(11):1743‐1749. 10.1002/cncr.28628.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever