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Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Patients’ perspectives on palliative chemotherapy of colorectal and non - colorectal cancer: a prospective study in a chemotherapy- experienced population

Authors: Marika Mende, Karolin Trautmann, Anke Rentsch, Beate Hornemann, Ulrich S Schuler, Gerhard Ehninger, Gunnar Folprecht

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

A better understanding of patients’ views on the benefit and burden obtained from palliative chemotherapy would facilitate shared decision making. We evaluated palliative cancer patients’ reported outcomes (PROs) for toxicity and investigated the survival threshold for which they would repeat chemotherapy (CTx).

Methods

Patients who had received a minimum of three months of palliative CTx for advanced colorectal (CRC) or non-colorectal (non-CRC: upper gastrointestinal, lung and head-and-neck) cancer were assessed by questionnaire. Patients were questioned about PROs for toxicity, subjective burden from side effects, and were asked for the survival threshold necessary for them to repeat CTx. Expected survival (sum of indicated survival threshold and median survival time with best supportive care) was compared to the patients’ actual survival.

Results

One hundred and thirty-four patients (CRC: 58; non-CRC: 76) were surveyed. The most frequent PRO- grade 3/4 toxicities were acne (12.8%), fatigue (9.0%), and diarrhea (8.5%). The symptom causing the highest subjective burden was fatigue and was worse than expected in 29.9% of the patients. The median survival threshold for which patients would repeat CTx was significantly longer in CRC than in non-CRC patients (p=0.01). Median expected survival was significantly longer than actual median survival (CRC: 44.0 months [22.0-65.9] compared with 30.0 months of actual survival [20.9-39.1]; non-CRC: 22.0 months [15.3-28.6] compared with 19.0 months of actual survival [15.1-22.9], p=0.03).

Conclusion

Fatigue deserves more attention when toxicity of treatment and symptoms of disease are explained to patients. Patients’ survival expectations from palliative chemotherapy are higher than previously described, exceed the median survival time known from phase III trials, and are significantly longer than their actual survival.
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Literature
1.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. 2010, Lyon, France: International Agency for Research on Cancer, Available from: http://globocan.iarc.fr/, Assessed on January 26, 2011 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. 2010, Lyon, France: International Agency for Research on Cancer, Available from: http://​globocan.​iarc.​fr/​, Assessed on January 26, 2011
2.
go back to reference Kopetz S, Chang GJ, Overman MJ, Eng C, Sargent DJ, Larson DW, et al: Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009, 27: 3677-3683. 10.1200/JCO.2008.20.5278.CrossRefPubMedPubMedCentral Kopetz S, Chang GJ, Overman MJ, Eng C, Sargent DJ, Larson DW, et al: Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009, 27: 3677-3683. 10.1200/JCO.2008.20.5278.CrossRefPubMedPubMedCentral
3.
go back to reference Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Costenla M, Boni C, et al: Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 study group. J Clin Oncol. 2006, 24: 4991-4997. 10.1200/JCO.2006.06.8429.CrossRefPubMed Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Costenla M, Boni C, et al: Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 study group. J Clin Oncol. 2006, 24: 4991-4997. 10.1200/JCO.2006.06.8429.CrossRefPubMed
4.
go back to reference Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al: Paclitaxel–carboplatin alone or with bevacizumab for non–small-cell lung cancer. N Engl J Med. 2006, 355: 2542-2550. 10.1056/NEJMoa061884.CrossRefPubMed Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al: Paclitaxel–carboplatin alone or with bevacizumab for non–small-cell lung cancer. N Engl J Med. 2006, 355: 2542-2550. 10.1056/NEJMoa061884.CrossRefPubMed
5.
go back to reference Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008, 359: 1116-1127. 10.1056/NEJMoa0802656.CrossRefPubMed Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008, 359: 1116-1127. 10.1056/NEJMoa0802656.CrossRefPubMed
6.
go back to reference United States Food and Drug Administration: Guidance for industry (draft). Patient-reported outcome measures: use in medical product development to support labeling claims. 2006, Rockville (MD): U.S: Department of Health and Human Services United States Food and Drug Administration: Guidance for industry (draft). Patient-reported outcome measures: use in medical product development to support labeling claims. 2006, Rockville (MD): U.S: Department of Health and Human Services
7.
go back to reference Matsuyama R, Reddy S, Smith TJ: Why do patients choose chemotherapy near the end of life? A review of the perspective of those facing death from cancer. J Clin Oncol. 2006, 24: 3490-3496. 10.1200/JCO.2005.03.6236.CrossRefPubMed Matsuyama R, Reddy S, Smith TJ: Why do patients choose chemotherapy near the end of life? A review of the perspective of those facing death from cancer. J Clin Oncol. 2006, 24: 3490-3496. 10.1200/JCO.2005.03.6236.CrossRefPubMed
8.
go back to reference Slevin ML, Stubbs L, Plant HJ, Wilson P, Gregory WM, Armes PJ, et al: Attitudes to chemotherapy: comparing views of patients with cancer with those of doctors, nurses, and general public. BMJ. 1990, 300: 1458-1460. 10.1136/bmj.300.6737.1458.CrossRefPubMedPubMedCentral Slevin ML, Stubbs L, Plant HJ, Wilson P, Gregory WM, Armes PJ, et al: Attitudes to chemotherapy: comparing views of patients with cancer with those of doctors, nurses, and general public. BMJ. 1990, 300: 1458-1460. 10.1136/bmj.300.6737.1458.CrossRefPubMedPubMedCentral
9.
go back to reference Love N, Bylund C, Meropol NJ, Marshall JL, Curley SA, Ellis LM, et al: How Well Do We Communicate with Patients Concerning Adjuvant Systemic Therapy? A Survey of 150 Colorectal Cancer Survivors. 2007, Proceedings of the ASCO Gastrointestinal Cancers Symposium, Abstract No: 239 Love N, Bylund C, Meropol NJ, Marshall JL, Curley SA, Ellis LM, et al: How Well Do We Communicate with Patients Concerning Adjuvant Systemic Therapy? A Survey of 150 Colorectal Cancer Survivors. 2007, Proceedings of the ASCO Gastrointestinal Cancers Symposium, Abstract No: 239
10.
go back to reference Balmer CE, Thomas P, Osborne RJ: Who wants second–line, palliative Chemotherapy?. Psychooncology. 2001, 10: 410-418. 10.1002/pon.538.CrossRefPubMed Balmer CE, Thomas P, Osborne RJ: Who wants second–line, palliative Chemotherapy?. Psychooncology. 2001, 10: 410-418. 10.1002/pon.538.CrossRefPubMed
11.
go back to reference Silvestri G, Pritchard R, Welch HG: Preferences for chemotherapy in patients with advanced non-small cell lung cancer: descriptive study based on scripted interviews. BMJ. 1998, 317: 771-775. 10.1136/bmj.317.7161.771.CrossRefPubMedPubMedCentral Silvestri G, Pritchard R, Welch HG: Preferences for chemotherapy in patients with advanced non-small cell lung cancer: descriptive study based on scripted interviews. BMJ. 1998, 317: 771-775. 10.1136/bmj.317.7161.771.CrossRefPubMedPubMedCentral
12.
go back to reference Brundage MD, Feldman-Stewart D, Cosby R, Gregg R, Dixon P, Youssef Y, et al: Cancer patients’ attitudes toward treatment options for advanced non-small cell lung cancer: implications for patient education and decision support. Patient Educ Couns. 2001, 45: 149-157. 10.1016/S0738-3991(01)00155-0.CrossRefPubMed Brundage MD, Feldman-Stewart D, Cosby R, Gregg R, Dixon P, Youssef Y, et al: Cancer patients’ attitudes toward treatment options for advanced non-small cell lung cancer: implications for patient education and decision support. Patient Educ Couns. 2001, 45: 149-157. 10.1016/S0738-3991(01)00155-0.CrossRefPubMed
13.
go back to reference Chu DT, Kim SW, Hsu HK, Cok G, Roubec J, Patil S, et al: Patients attitudes towards chemotherapy and survival: a prospective observational study in advanced non-small cell lung cancer. Lung Cancer. 2009, 66: 250-256. 10.1016/j.lungcan.2009.01.022.CrossRefPubMed Chu DT, Kim SW, Hsu HK, Cok G, Roubec J, Patil S, et al: Patients attitudes towards chemotherapy and survival: a prospective observational study in advanced non-small cell lung cancer. Lung Cancer. 2009, 66: 250-256. 10.1016/j.lungcan.2009.01.022.CrossRefPubMed
14.
go back to reference Kim MK, Lee JL, Hyun MS, Do YR, Song HS, Kim JG, et al: Palliative chemotherapy preferences and factors that influence patient choice in incurable advanced cancer. Jpn J Clin Oncol. 2008, 38: 64-70. 10.1093/jjco/hym147.CrossRefPubMed Kim MK, Lee JL, Hyun MS, Do YR, Song HS, Kim JG, et al: Palliative chemotherapy preferences and factors that influence patient choice in incurable advanced cancer. Jpn J Clin Oncol. 2008, 38: 64-70. 10.1093/jjco/hym147.CrossRefPubMed
15.
go back to reference Walling A, Lorenz KA, Dy SM, Naeim A, Sanati H, Asch SM, et al: Evidence-based recommendations for information and care planning in cancer care. J Clin Oncol. 2008, 26: 3896-3902. 10.1200/JCO.2007.15.9509.CrossRefPubMed Walling A, Lorenz KA, Dy SM, Naeim A, Sanati H, Asch SM, et al: Evidence-based recommendations for information and care planning in cancer care. J Clin Oncol. 2008, 26: 3896-3902. 10.1200/JCO.2007.15.9509.CrossRefPubMed
16.
go back to reference Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0, DCTD, NCI, NIH, DHHS March 31, 2003: (http://ctep.cancer.gov), Publish Date: June 10, 2003 Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0, DCTD, NCI, NIH, DHHS March 31, 2003: (http://​ctep.​cancer.​gov), Publish Date: June 10, 2003
17.
go back to reference Serlin RC, Mendoza TR, Nakamura Y, Edwards KR, Cleeland CS: When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain. 1995, 61: 277-284. 10.1016/0304-3959(94)00178-H.CrossRefPubMed Serlin RC, Mendoza TR, Nakamura Y, Edwards KR, Cleeland CS: When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain. 1995, 61: 277-284. 10.1016/0304-3959(94)00178-H.CrossRefPubMed
18.
go back to reference Sigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983, 67: 361-370. 10.1111/j.1600-0447.1983.tb09716.x.CrossRef Sigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983, 67: 361-370. 10.1111/j.1600-0447.1983.tb09716.x.CrossRef
19.
go back to reference Bjelland I, Dahl AA, Haug TT, Neckelmann D: The validity of the hospital anxiety and depression scale an updated literature review. J Psychosom Res. 2002, 52: 69-77. 10.1016/S0022-3999(01)00296-3.CrossRefPubMed Bjelland I, Dahl AA, Haug TT, Neckelmann D: The validity of the hospital anxiety and depression scale an updated literature review. J Psychosom Res. 2002, 52: 69-77. 10.1016/S0022-3999(01)00296-3.CrossRefPubMed
20.
go back to reference Likert R: A technique for the measurement of attitudes. Arch Psych. 1932, 140: 1-55. Likert R: A technique for the measurement of attitudes. Arch Psych. 1932, 140: 1-55.
21.
go back to reference Group CCC, Simmonds PC: Palliative chemotherapy for advanced colorectal cancer: systematic review and meta – analysis. BMJ. 2000, 321: 531-535.CrossRef Group CCC, Simmonds PC: Palliative chemotherapy for advanced colorectal cancer: systematic review and meta – analysis. BMJ. 2000, 321: 531-535.CrossRef
22.
go back to reference Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE: Chemotherapy in advanced gastric cancer: a systematic review and meta - analysis based on aggregate data. J Clin Oncol. 2006, 24: 2903-2909. 10.1200/JCO.2005.05.0245.CrossRefPubMed Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE: Chemotherapy in advanced gastric cancer: a systematic review and meta - analysis based on aggregate data. J Clin Oncol. 2006, 24: 2903-2909. 10.1200/JCO.2005.05.0245.CrossRefPubMed
23.
go back to reference Rapp E, Pater JL, Willan A, Cormier Y, Murray N, Evans WK, et al: Chemotherapy Can prolong survival in patients with advanced non-small-cell lung cancer-report of a Canadian multicenter randomized trial. J Clin Oncol. 1988, 6: 633-641.PubMed Rapp E, Pater JL, Willan A, Cormier Y, Murray N, Evans WK, et al: Chemotherapy Can prolong survival in patients with advanced non-small-cell lung cancer-report of a Canadian multicenter randomized trial. J Clin Oncol. 1988, 6: 633-641.PubMed
24.
go back to reference Stell PM, Morton RP, Singh SD: Squamous carcinoma of the head and neck: the untreated patient. Clin Otolaryngol Allied Sci. 1983, 8: 7-13. 10.1111/j.1365-2273.1983.tb01665.x.CrossRefPubMed Stell PM, Morton RP, Singh SD: Squamous carcinoma of the head and neck: the untreated patient. Clin Otolaryngol Allied Sci. 1983, 8: 7-13. 10.1111/j.1365-2273.1983.tb01665.x.CrossRefPubMed
25.
go back to reference Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, et al: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009, 360: 1408-1417. 10.1056/NEJMoa0805019.CrossRefPubMed Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, et al: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009, 360: 1408-1417. 10.1056/NEJMoa0805019.CrossRefPubMed
26.
go back to reference Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, et al: Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009, 373: 1525-1531. 10.1016/S0140-6736(09)60569-9.CrossRefPubMed Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, et al: Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009, 373: 1525-1531. 10.1016/S0140-6736(09)60569-9.CrossRefPubMed
27.
go back to reference Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al: Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008, 358: 36-46. 10.1056/NEJMoa073149.CrossRefPubMed Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al: Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008, 358: 36-46. 10.1056/NEJMoa073149.CrossRefPubMed
29.
go back to reference Ahlberg K, Ekman T, Gaston-Johansson F, Mock V: Assessment and management of cancer-related fatigue in adults. Lancet. 2003, 362: 640-650. 10.1016/S0140-6736(03)14186-4.CrossRefPubMed Ahlberg K, Ekman T, Gaston-Johansson F, Mock V: Assessment and management of cancer-related fatigue in adults. Lancet. 2003, 362: 640-650. 10.1016/S0140-6736(03)14186-4.CrossRefPubMed
30.
go back to reference Curt GA, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, et al: Impact of cancer-related fatigue on the lives of patients: new findings from the fatigue coalition. Oncologist. 2000, 5: 353-360. 10.1634/theoncologist.5-5-353.CrossRefPubMed Curt GA, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, et al: Impact of cancer-related fatigue on the lives of patients: new findings from the fatigue coalition. Oncologist. 2000, 5: 353-360. 10.1634/theoncologist.5-5-353.CrossRefPubMed
31.
go back to reference Olver IN, Taylor AE, Whitford HS: Relationships between patients’ pre-treatment expectations of toxicities and post chemotherapy experiences. Psychooncology. 2005, 14: 25-33. 10.1002/pon.804.CrossRefPubMed Olver IN, Taylor AE, Whitford HS: Relationships between patients’ pre-treatment expectations of toxicities and post chemotherapy experiences. Psychooncology. 2005, 14: 25-33. 10.1002/pon.804.CrossRefPubMed
32.
go back to reference Sauer H: Basisinformation zum Aufklärungsgespräch Zytostatische Chemotherapie. 2009, Erlangen: proCompliance in Thieme GmbH Sauer H: Basisinformation zum Aufklärungsgespräch Zytostatische Chemotherapie. 2009, Erlangen: proCompliance in Thieme GmbH
33.
go back to reference Brundage MD, Davidson JR, Mackillop WJ: Trading treatment toxicity for survival in locally advanced non-small cell lung cancer. J Clin Oncol. 1997, 15: 330-340.PubMed Brundage MD, Davidson JR, Mackillop WJ: Trading treatment toxicity for survival in locally advanced non-small cell lung cancer. J Clin Oncol. 1997, 15: 330-340.PubMed
34.
go back to reference Weeks JC, Catalano PJ, Cronin A, Finkelman MD, Mack JW, Keating NL, et al: Patient’s expectations about effects of chemotherapy for advanced cancer. N Engl J Med. 2012, 367: 1616-1625. 10.1056/NEJMoa1204410.CrossRefPubMedPubMedCentral Weeks JC, Catalano PJ, Cronin A, Finkelman MD, Mack JW, Keating NL, et al: Patient’s expectations about effects of chemotherapy for advanced cancer. N Engl J Med. 2012, 367: 1616-1625. 10.1056/NEJMoa1204410.CrossRefPubMedPubMedCentral
35.
go back to reference Chow E, Andersson L, Wong R, Vachon M, Hruby G, Franssen E, et al: Patients with advanced cancer: a survey of the understanding of their illness and expectations from palliative radiotherapy for symptomatic metastases. Clin Oncol. 2001, 13: 204-208. Chow E, Andersson L, Wong R, Vachon M, Hruby G, Franssen E, et al: Patients with advanced cancer: a survey of the understanding of their illness and expectations from palliative radiotherapy for symptomatic metastases. Clin Oncol. 2001, 13: 204-208.
36.
go back to reference Wright AA, Zhang B, Ray A, Mack JW, Trice E, Balboni T, et al: Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. JAMA. 2008, 300: 1665-1673. 10.1001/jama.300.14.1665.CrossRefPubMedPubMedCentral Wright AA, Zhang B, Ray A, Mack JW, Trice E, Balboni T, et al: Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. JAMA. 2008, 300: 1665-1673. 10.1001/jama.300.14.1665.CrossRefPubMedPubMedCentral
37.
go back to reference Mystakidou K, Tsilika E, Parpa E, Athanasouli P, Galanos A, Anna P, Illness-Related Hopelessness in Advanced Cancer, et al: Influence of anxiety, depression, and preparatory grief. Arch Psychiatr Nurs. 2009, 23: 138-147. 10.1016/j.apnu.2008.04.008.CrossRefPubMed Mystakidou K, Tsilika E, Parpa E, Athanasouli P, Galanos A, Anna P, Illness-Related Hopelessness in Advanced Cancer, et al: Influence of anxiety, depression, and preparatory grief. Arch Psychiatr Nurs. 2009, 23: 138-147. 10.1016/j.apnu.2008.04.008.CrossRefPubMed
38.
go back to reference Pessin H, Rosenfeld B, Breitbart W: Assessing psychological distress near the end of life. Am Behav Sci. 2002, 46: 357-372. 10.1177/000276402237769.CrossRef Pessin H, Rosenfeld B, Breitbart W: Assessing psychological distress near the end of life. Am Behav Sci. 2002, 46: 357-372. 10.1177/000276402237769.CrossRef
39.
go back to reference Weis J, Boehncke A: Psychische Komorbidität bei Krebserkrankungen. Bundesgesundheitsbl. 2011, 54: 46-51. 10.1007/s00103-010-1184-y.CrossRef Weis J, Boehncke A: Psychische Komorbidität bei Krebserkrankungen. Bundesgesundheitsbl. 2011, 54: 46-51. 10.1007/s00103-010-1184-y.CrossRef
40.
go back to reference Zabora J, Brintzenhofeszoc K, Jacobsen P, Curbow B, Piantadosi S, Hooker C, et al: A new psychosocial screening instrument for use with cancer patients. Psychosomatics. 2001, 42: 241-246. 10.1176/appi.psy.42.3.241.CrossRefPubMed Zabora J, Brintzenhofeszoc K, Jacobsen P, Curbow B, Piantadosi S, Hooker C, et al: A new psychosocial screening instrument for use with cancer patients. Psychosomatics. 2001, 42: 241-246. 10.1176/appi.psy.42.3.241.CrossRefPubMed
Metadata
Title
Patients’ perspectives on palliative chemotherapy of colorectal and non - colorectal cancer: a prospective study in a chemotherapy- experienced population
Authors
Marika Mende
Karolin Trautmann
Anke Rentsch
Beate Hornemann
Ulrich S Schuler
Gerhard Ehninger
Gunnar Folprecht
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-66

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