Reducing the Symptom Burden Produced by Aggressive Cancer Therapies

Summary

Principal Investigator: C S Cleeland
Affiliation: The University of Texas
Country: USA
Abstract: DESCRIPTION (provided by applicant): We propose clinical trials that will assess the effectiveness of using a combination of therapies to reduce symptom burden during aggressive cancer treatment. The target populations for study are patients undergoing chemoradiotherapy for head and neck cancer or lung cancer. The high symptom burden caused by aggressive treatment of these cancers may become so severe that patients may be forced to interrupt therapy, may need to make unscheduled visits for emergency symptom care, and/or may have difficulty maintaining vocational and family commitments during therapy and for weeks thereafter. The combined interventions we will test are derived from a theoretical model based on evidence that treatment-produced inflammation is a major cause for many symptoms, such as fatigue, appetite loss, emotional distress, and pain, and that modulation of this inflammation and its consequences will significantly reduce symptom burden. Combinations of therapy will include inhibitors of NF-:B (a precursor molecule for inflammation), inhibitors of inflammatory cytokines, and an antidepressant (bupropion) that also has inflammatory action. We will include a wakefulness-promoting agent (modafinil) that may modify the effects of inflammatory cytokines on the brain. We will utilize new methods of assessment (a computer-based telephone assessment system combined with symptom-assessment questionnaires developed for each disease condition) to frequently monitor the severity of treatment-specific symptoms over the time of the study. Symptoms will be monitored twice a week using the telephone-based assessment system. This method will allow us to derive an area under the curve (AUC) for multiple symptoms for each patient group across the period of treatment. Changes in AUC for established severe treatment-related symptoms for each group will be the primary trial outcome variable. A key component of this proposal is the use of a Bayesian adaptive design to rapidly assess the efficacy of the several treatments and treatment synergies. Such a design take advantage of accumulating trial results by assessing them periodically;the trial can then be adjusted by slowing (or stopping) ineffective interventions or by expanding patient accrual to better-performing therapies, potentially leading to smaller, more informative trials and better treatments for patients. With now-available increases in computational power and newer modeling methods, these adaptive methods are increasingly being used in clinical research for curative therapies but have yet to be used in symptom research, where their advantages in maximizing treatment benefits within the trial period are attractive. The Bayesian adaptive approach to the assessment of symptom-focused treatments may be an inportant avenue to address the critical need for an evidence base for clinical decisions about symptom control. PUBLIC HEALTH RELEVANCE: The significance of this research is that it addresses methods of reducing the symptoms and side effects of aggressive cancer therapy. We will use new developments in clinical trial design that let us identify best combined treatments for symptom reduction as quickly as possible, and let us administer the effective treatment combinations to more patients within the period of the clinical trial. We aim to develop a strategy using several drugs working together to prevent or ameliorate multiple treatment-related symptoms, such as fatigue, pain, sleep disturbance, and poor appetite, for patients treated for head and neck cancer or lung cancer. The ultimate goal of this research is to be able to administer the best available curative therapy to the largest number of patients with the least treatment-related symptom burden.
Funding Period: ----------------1986 - ---------------2013-
more information: NIH RePORT

Top Publications

  1. ncbi Longitudinal study of the relationship between chemoradiation therapy for non-small-cell lung cancer and patient symptoms
    Xin Shelley Wang
    Department of Symptom Research, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    J Clin Oncol 24:4485-91. 2006
  2. pmc Prospective, observational study of pain and analgesic prescribing in medical oncology outpatients with breast, colorectal, lung, or prostate cancer
    Michael J Fisch
    The University of Texas MD Anderson Cancer Center, Houston, TX, USA
    J Clin Oncol 30:1980-8. 2012
  3. pmc Phase 1/2 trial of single-session stereotactic body radiotherapy for previously unirradiated spinal metastases
    Amit K Garg
    Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX, USA
    Cancer 118:5069-77. 2012
  4. pmc Translational approaches to treatment-induced symptoms in cancer patients
    Robert Dantzer
    Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Nat Rev Clin Oncol 9:414-26. 2012
  5. pmc High symptom burden prior to radiation therapy for head and neck cancer: a patient-reported outcomes study
    G Brandon Gunn
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
    Head Neck 35:1490-8. 2013
  6. pmc Bayesian adaptive phase II screening design for combination trials
    Chunyan Cai
    Biostatistics Epidemiology Research Design Core, Center for Clinical and Translational Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA
    Clin Trials 10:353-62. 2013
  7. pmc Prognostic value of patient-reported symptom interference in patients with late-stage lung cancer
    Bradley J Barney
    Department of Mathematics and Statistics, Kennesaw State University, Kennesaw, Georgia
    Qual Life Res 22:2143-50. 2013
  8. pmc Quantifying fatigue in (long-term) colorectal cancer survivors: a study from the population-based patient reported outcomes following initial treatment and long term evaluation of survivorship registry
    Melissa S Y Thong
    CoRPS, Dept of Medical and Clinical Psychology, Tilburg University, The Netherlands Comprehensive Cancer Centre South CCCS, Eindhoven Cancer Registry, Eindhoven, The Netherlands
    Eur J Cancer 49:1957-66. 2013
  9. pmc Using group-based trajectory modeling to examine heterogeneity of symptom burden in patients with head and neck cancer undergoing aggressive non-surgical therapy
    Qiuling Shi
    Department of Symptom Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1450, Houston, TX, 77030, USA
    Qual Life Res 22:2331-9. 2013
  10. pmc The validity and utility of the M. D. Anderson Symptom Inventory in patients with breast cancer: evidence from the symptom outcomes and practice patterns data from the eastern cooperative oncology group
    Tito R Mendoza
    Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX Electronic address
    Clin Breast Cancer 13:325-34. 2013

Scientific Experts

  • Xin Shelley Wang
  • C S Cleeland
  • Tito R Mendoza
  • Qiuling Shi
  • Michael J Fisch
  • Fengmin Zhao
  • Bharat B Aggarwal
  • Sahdeo Prasad
  • Subash C Gupta
  • David I Rosenthal
  • Charles Lu
  • Lynne I Wagner
  • G Brandon Gunn
  • Vivek R Yadav
  • Desiree Jones
  • Ehab Y Hanna
  • Clifton D Fuller
  • Chunyan Cai
  • Bradley J Barney
  • Melissa S Y Thong
  • Valen E Johnson
  • Victor T Chang
  • David Cella
  • Amit K Garg
  • Robert Dantzer
  • J Boyette-Davis
  • Richard J Swartz
  • Ji Hye Kim
  • William H Morrison
  • Edith P Mitchell
  • James F Cleary
  • Adam S Garden
  • Ann M O'Mara
  • Katherine A Hutcheson
  • Linda J Patrick-Miller
  • Ibrahima Gning
  • Valery E P P Lemmens
  • Floortje Mols
  • Beth M Beadle
  • Steven J Frank
  • Tineke J Smilde
  • Ying Yuan
  • Zhongxing Liao
  • Lonneke V van de Poll-Franse
  • Eric L Chang
  • Matthias Weiss
  • Ju Whei Lee
  • Lori M Minasian
  • Mary Frances McAleer
  • Almon S Shiu
  • Syed Azeem
  • Barry W Brown
  • Pamela Allen
  • Worta McCaskill-Stevens
  • Paul D Brown
  • Laurence D Rhines
  • James Yang
  • Judith B Manola
  • Mary W Meagher
  • Patricia Grossman
  • Erik K Frija
  • Jun Wang
  • Lori McLeod
  • Bryce Reeve
  • ROCHELLE TRACTENBERG
  • Theresa Gilligan
  • H Zhang
  • Bokyung Sung
  • Ramaswamy Kannappan
  • W Xin
  • Ken Bollen
  • Herle McGowan
  • MARK PRICE
  • Simone Reuter
  • Bruce Rapkin
  • Carolyn Schwartz
  • Lauren Nelson
  • P M Dougherty
  • Li Cai
  • Knashawn Morales
  • Valerie Williams
  • Carmen Rivera-Medina
  • Diane L Fairclough
  • Jayaraj Ravindran
  • THOMAS ATKINSON
  • Betsy Feldman
  • Cheryl Coon
  • Ethan Basch

Detail Information

Publications37

  1. ncbi Longitudinal study of the relationship between chemoradiation therapy for non-small-cell lung cancer and patient symptoms
    Xin Shelley Wang
    Department of Symptom Research, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    J Clin Oncol 24:4485-91. 2006
    ....
  2. pmc Prospective, observational study of pain and analgesic prescribing in medical oncology outpatients with breast, colorectal, lung, or prostate cancer
    Michael J Fisch
    The University of Texas MD Anderson Cancer Center, Houston, TX, USA
    J Clin Oncol 30:1980-8. 2012
    ..Pain is prevalent among patients with cancer, yet pain management patterns in outpatient oncology are poorly understood...
  3. pmc Phase 1/2 trial of single-session stereotactic body radiotherapy for previously unirradiated spinal metastases
    Amit K Garg
    Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX, USA
    Cancer 118:5069-77. 2012
    ..In this phase 1/2 study, the authors tested the hypothesis that single-fraction stereotactic body radiotherapy (SBRT) for previously unirradiated spinal metastases is a safe, feasible, and efficacious treatment approach...
  4. pmc Translational approaches to treatment-induced symptoms in cancer patients
    Robert Dantzer
    Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Nat Rev Clin Oncol 9:414-26. 2012
    ..Ultimately, this knowledge will allow derivation of mechanism-based interventions to prevent or alleviate cancer-related symptoms...
  5. pmc High symptom burden prior to radiation therapy for head and neck cancer: a patient-reported outcomes study
    G Brandon Gunn
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
    Head Neck 35:1490-8. 2013
    ..As a first step toward developing effective strategies to control symptoms associated with head and neck cancer (HNC) and its treatment, we sought to describe the pattern of symptoms experienced before radiation therapy...
  6. pmc Bayesian adaptive phase II screening design for combination trials
    Chunyan Cai
    Biostatistics Epidemiology Research Design Core, Center for Clinical and Translational Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA
    Clin Trials 10:353-62. 2013
    ....
  7. pmc Prognostic value of patient-reported symptom interference in patients with late-stage lung cancer
    Bradley J Barney
    Department of Mathematics and Statistics, Kennesaw State University, Kennesaw, Georgia
    Qual Life Res 22:2143-50. 2013
    ..Several PROs derived from the 12-item Short-Form Health Survey (SF-12) and M. D. Anderson Symptom Inventory (MDASI) were investigated for association with OS, with adjustments for other factors, including performance status...
  8. pmc Quantifying fatigue in (long-term) colorectal cancer survivors: a study from the population-based patient reported outcomes following initial treatment and long term evaluation of survivorship registry
    Melissa S Y Thong
    CoRPS, Dept of Medical and Clinical Psychology, Tilburg University, The Netherlands Comprehensive Cancer Centre South CCCS, Eindhoven Cancer Registry, Eindhoven, The Netherlands
    Eur J Cancer 49:1957-66. 2013
    ..Few studies specifically focus on fatigue of (long-term) colorectal cancer (CRC) survivors or compare fatigue levels with a normative population. Association between surviving multiple primary cancers and fatigue is also explored...
  9. pmc Using group-based trajectory modeling to examine heterogeneity of symptom burden in patients with head and neck cancer undergoing aggressive non-surgical therapy
    Qiuling Shi
    Department of Symptom Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1450, Houston, TX, 77030, USA
    Qual Life Res 22:2331-9. 2013
    ..We applied group-based trajectory modeling (GBTM) to describe the heterogeneity of symptom burden among patients with head and neck cancer and to identify subgroups with distinct symptom-development trajectories...
  10. pmc The validity and utility of the M. D. Anderson Symptom Inventory in patients with breast cancer: evidence from the symptom outcomes and practice patterns data from the eastern cooperative oncology group
    Tito R Mendoza
    Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX Electronic address
    Clin Breast Cancer 13:325-34. 2013
    ..Although the original MDASI validation study encompassed various cancer types, the instrument's psychometric properties have not been examined in a homogenous sample of patients with breast cancer in a national multicenter study...
  11. pmc The symptom burden of cancer: Evidence for a core set of cancer-related and treatment-related symptoms from the Eastern Cooperative Oncology Group Symptom Outcomes and Practice Patterns study
    Charles S Cleeland
    Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas
    Cancer 119:4333-40. 2013
    ..Using data from a large, multicenter, prospective study, the authors assessed the effects of disease site and stage on the percentages of patients rating these proposed symptoms as moderate to severe...
  12. pmc The validity and utility of the MD Anderson Symptom Inventory in patients with prostate cancer: evidence from the Symptom Outcomes and Practice Patterns (SOAPP) data from the Eastern Cooperative Oncology Group
    Desiree Jones
    Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX Electronic address
    Clin Genitourin Cancer 12:41-9. 2014
    ..Although the original MDASI validation study encompassed various cancer types, the instrument's psychometric properties have not been examined in a large homogeneous sample of patients with prostate cancer...
  13. pmc Predictors of significant worsening of patient-reported fatigue over a 1-month timeframe in ambulatory patients with common solid tumors
    Michael J Fisch
    Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
    Cancer 120:442-50. 2014
    ..Understanding the determinants of fatigue worsening may help distinguish between different fatigue phenotypes and inform clinical trial designs...
  14. pmc Determinants of pain severity changes in ambulatory patients with cancer: an analysis from Eastern Cooperative Oncology Group trial E2Z02
    Fengmin Zhao
    Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA Victor T Chang, Veterans Affairs New Jersey Health Care System Rutgers New Jersey Medical School, East Orange, NJ Charles Cleeland and Michael J Fisch, The University of Texas MD Anderson Cancer Center, Houston, TX James F Cleary, University of Wisconsin, Madison, WI Edith P Mitchell, Thomas Jefferson University, Philadelphia, PA and Lynne I Wagner, Northwestern University Feinberg School of Medicine, Chicago, IL
    J Clin Oncol 32:312-9. 2014
    ..To understand changes in pain severity over time and to explore the factors associated with pain changes in ambulatory patients with solid tumors...
  15. pmc Patterns of symptom burden during radiotherapy or concurrent chemoradiotherapy for head and neck cancer: a prospective analysis using the University of Texas MD Anderson Cancer Center Symptom Inventory-Head and Neck Module
    David I Rosenthal
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
    Cancer 120:1975-84. 2014
    ..The goals were to understand the onset and trajectory of specific symptoms and their severity, identify clusters, and facilitate symptom interventions and clinical trial design...
  16. pmc Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals
    Subash C Gupta
    Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Cancer Metastasis Rev 29:405-34. 2010
    ..Various cell signaling pathways that are modulated by these agents will also be discussed...
  17. pmc Pathophysiology of cancer-related fatigue
    Xin Shelley Wang
    Department of Symptom Research, University of Texas M D Anderson Cancer Center, Houston, Texas, USA
    Clin J Oncol Nurs 12:11-20. 2008
    ..Pathophysiologic research in CRF could be applied in the clinic to improve CRF diagnosis and to enable administration of mechanism-driven interventions. A targeted intervention study with CRF as a primary end point also would be useful...
  18. pmc The king's foot of patient-reported outcomes: current practices and new developments for the measurement of change
    Richard J Swartz
    Jones Graduate School of Business, Rice University, Houston, TX, USA
    Qual Life Res 20:1159-67. 2011
    ..This white paper summarizes these issues and provides recommendations and possible paths for dealing with the complexities of measuring change...
  19. pmc Serum interleukin-6 predicts the development of multiple symptoms at nadir of allogeneic hematopoietic stem cell transplantation
    Xin Shelley Wang
    Department of Symptom Research, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 113:2102-9. 2008
    ..However, the mechanism underlying the development of multiple symptoms has not been established...
  20. ncbi The measurement of pain from metastatic bone disease: capturing the patient's experience
    Charles S Cleeland
    Department of Symptom Research, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 12:6236s-6242s. 2006
    ..These and other considerations in the design of clinical trials are discussed...
  21. pmc Assessing persistent cancer pain: a comparison of current pain ratings and pain recalled from the past week
    Qiuling Shi
    Department of Symptom Research, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Pain Symptom Manage 37:168-74. 2009
    ..Our results provide information that might guide the choice of recall period for cancer clinical trials with pain as a self-reported outcome...
  22. pmc Prognostic value of symptom burden for overall survival in patients receiving chemotherapy for advanced nonsmall cell lung cancer
    Xin Shelley Wang
    Department of Symptom Research, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cancer 116:137-45. 2010
    ..However, translating patient-reported outcomes into useful prognostic information for individual patients has been problematic...
  23. pmc Impact of cultural and linguistic factors on symptom reporting by patients with cancer
    Xin Shelley Wang
    Department of Symptom Research, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1450, Houston, TX 77030, USA
    J Natl Cancer Inst 102:732-8. 2010
    ..In multinational clinical trials, cultural and linguistic variations in patient-reported outcomes instruments could confound the interpretation of study results...
  24. pmc Inflammatory cytokines are associated with the development of symptom burden in patients with NSCLC undergoing concurrent chemoradiation therapy
    Xin Shelley Wang
    Department of Symptom Research, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Brain Behav Immun 24:968-74. 2010
    ....
  25. pmc Levels of symptom burden during chemotherapy for advanced lung cancer: differences between public hospitals and a tertiary cancer center
    Charles S Cleeland
    The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    J Clin Oncol 29:2859-65. 2011
    ..We compared risk factors for high disease- and treatment-related symptom burden over 15 weeks of therapy in medically underserved patients with advanced non-small-cell lung cancer and in patients treated at a tertiary cancer center...
  26. pmc ROS and CHOP are critical for dibenzylideneacetone to sensitize tumor cells to TRAIL through induction of death receptors and downregulation of cell survival proteins
    Sahdeo Prasad
    Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 71:538-49. 2011
    ..Overall, our results show that DBA potentiates TRAIL-induced apoptosis through downregulation of cell survival proteins and upregulation of death receptors via activation of ROS and CHOP mediated pathways...
  27. pmc Intraepidermal nerve fiber loss corresponds to the development of taxol-induced hyperalgesia and can be prevented by treatment with minocycline
    J Boyette-Davis
    Department of Anesthesiology and Pain Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA
    Pain 152:308-13. 2011
    ..The progression of Taxol-induced mechanical hypersensitivity coincides with loss of intraepidermal nerve fibers, and the hyperalgesia and nerve fiber loss were prevented with minocycline treatment...
  28. pmc The role of chalcones in suppression of NF-κB-mediated inflammation and cancer
    Vivek R Yadav
    Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston 77030, TX, USA
    Int Immunopharmacol 11:295-309. 2011
    ..How these chalcones modulate inflammatory pathways, tumorigenesis and immune system is the focus of this review...
  29. pmc Chemosensitization of tumors by resveratrol
    Subash C Gupta
    Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA
    Ann N Y Acad Sci 1215:150-60. 2011
    ..The potential mechanisms underlying this dual effect are discussed. Overall, studies suggest that resveratrol can be used to sensitize tumors to standard cancer chemotherapeutics...
  30. pmc Automated symptom alerts reduce postoperative symptom severity after cancer surgery: a randomized controlled clinical trial
    Charles S Cleeland
    The University of Texas MD Anderson Cancer Center, Department of Symptom Research, 1515 Holcombe Blvd, Box 1450, Houston, TX 77030, USA
    J Clin Oncol 29:994-1000. 2011
    ..This study examined whether at-home symptom monitoring plus feedback to clinicians about severe symptoms contributes to more effective postoperative symptom control...
  31. pmc Measuring the symptom burden of lung cancer: the validity and utility of the lung cancer module of the M. D. Anderson Symptom Inventory
    Tito R Mendoza
    Department of Symptom Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1450, Houston, Texas 77030, USA
    Oncologist 16:217-27. 2011
    ....
  32. pmc Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1-2 trial
    Xin Shelley Wang
    Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Lancet Oncol 13:395-402. 2012
    ..We investigated the clinical benefit of SBRT for managing spinal metastases and reducing cancer-related symptoms...
  33. pmc Serum sTNF-R1, IL-6, and the development of fatigue in patients with gastrointestinal cancer undergoing chemoradiation therapy
    Xin Shelley Wang
    Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Brain Behav Immun 26:699-705. 2012
    ..0001). This longitudinal study suggests a role for over-expressed sTNF-R1 and IL-6 in the development of fatigue and other severe sickness symptoms during CXRT in patients with colorectal or esophageal cancer...
  34. pmc Symptom burden in cancer survivors 1 year after diagnosis: a report from the American Cancer Society's Studies of Cancer Survivors
    Qiuling Shi
    Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Cancer 117:2779-90. 2011
    ....