Exercise as Medicine in the Management of Pancreatic Cancer: A Case Study

Cormie, Prue1; Spry, Nigel1,2,3; Jasas, Kevin4; Johansson, Mikael5; Yusoff, Ian F.3,6; Newton, Robert U.1; Galvão, Daniel A.1

Medicine & Science in Sports & Exercise:
doi: 10.1249/MSS.0000000000000160
Clinical Sciences

Introduction: Given the poor prognosis for patients diagnosed with pancreatic cancer, therapies that enhance the ability to tolerate adjuvant treatments, reduce the loss of physical functioning and optimize quality of life are critically important. Exercise may represent such a therapy; however, no previous research has investigated the potential impact of exercise on outcomes in pancreatic cancer patients.

Purpose: This study aimed to determine the safety and efficacy of a 6-month supervised exercise program in a pancreatic cancer patient undergoing adjuvant treatment.

Methods: A case study was performed on a 49-yr-old male diagnosed with stage IIb pancreatic cancer. The patient had surgery (Whipple resection) followed by adjuvant chemotherapy (gemcitabine and fluorouracil) and radiotherapy (45 Gy). The patient initiated a supervised exercise program involving twice weekly resistance and aerobic exercise sessions during adjuvant therapy. Outcomes were assessed at baseline and after 3 and 6 months of exercise.

Results: The exercise program was well tolerated with 73% attendance throughout the 6 months. No treatment toxicities prevented the patient from complying with adjuvant treatment plans. Considerable improvements were observed at both 3- and 6-month assessment points for all measures of physical capacity and functional ability, lean mass, physical activity levels, general health and disease-specific quality of life, cancer-related fatigue, sleep quality, and psychological distress.

Conclusions: In this first reported clinical case, exercise led to improvements in a variety of patient outcomes during adjuvant therapy for pancreatic cancer. This initial evidence has important clinical implications, indicating that exercise may be an effective adjunct therapy for the management of pancreatic cancer. Future trials are needed to confirm and expand our initial findings.

Author Information

1Edith Cowan University Health and Wellness Institute, Edith Cowan University, Joondalup, AUSTRALIA; 2Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, AUSTRALIA; 3Faculty of Medicine, University of Western Australia, AUSTRALIA; 4Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, AUSTRALIA; 5Department of General Surgery, Sir Charles Gairdner Hospital, Nedlands, AUSTRALIA; 6Department of Gastroenterology, Sir Charles Gairdner Hospital, Nedlands, AUSTRALIA

Address for correspondence: Prue Cormie, Ph.D., ECU Health and Wellness Institute, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia; E-mail: p.cormie@ecu.edu.au.

Submitted for publication June 2013.

Accepted for publication September 2013.

Article Outline

Pancreatic cancer is relatively uncommon, accounting for only 2.7% of all cancer diagnoses in the United States (33). However, it is still a highly fatal disease with a 5-yr relative survival rate of only 6% (22%, 9%, and 2% for localized, regional, and distant disease, respectively), resulting in pancreatic cancer accounting for 6.5% of all cancer deaths (33). Progression in treatment modalities has had minimal effect on survival, with little change in the survival rate for the past 30 yr (33). The common treatment for patients with resectable disease is surgery followed by adjuvant chemotherapy (and to a lesser extent radiotherapy); however, the vast majority of patients are diagnosed with unresectable disease (∼80%–90%; treatment generally involves biliary stents and biliary bypass surgery for palliation) (23,31,34). Pancreatic cancer has a profound impact on quality of life with patients commonly experiencing adverse effects including significant weight loss, cancer-related fatigue, nausea, and psychological distress (3,7,18,28). Given the poor prognosis for patients diagnosed with pancreatic cancer, therapies that optimize quality of life and maintain physical function are critically important.

Exercise has established efficacy for counteracting many adverse side effects of cancer treatment, leading to improved functional ability and quality of life (9,29,30). Emerging observational evidence also suggests that exercise has a protective effect against cancer-specific mortality (21,24,26). The strength of evidence has led to the development of international guidelines recommending that cancer patients “avoid inactivity” even if undergoing difficult treatments (29,30). Thus, exercise may have an important role in the effective management of pancreatic cancer. However, no previous single case clinical study or any early phase clinical trial exists on the potential impact of exercise to improve outcomes in patients diagnosed with pancreatic cancer, with current exercise oncology knowledge largely arising from investigations involving breast and prostate cancers (30). Here we report for the first time the impact of a 6-month supervised exercise program in a pancreatic cancer patient undergoing adjuvant treatment. This is the first empirical examination of the safety and efficacy of exercise in pancreatic cancer.

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This case study involved a 49-yr-old man (weight = 102.3 kg, height = 171.3 cm) with a histological diagnosis of pancreatic cancer. The patient is married, has a tertiary education, is a nonsmoker, and was unemployed at study entry (he quit his full-time job to take on a consulting role just before his cancer diagnosis). He was diagnosed with an invasive colloid adenocarcinoma in June 2012 (T2 N1 M0 stage IIb; 20 mm invasive component with 3 of 21 lymph nodes involved). The cancer diagnosis came after hospitalization for obstructive jaundice requiring a 10-d in-patient stay in May–June 2012. The patient has a history of chronic pancreatitis since 1993, and the cancer diagnosis arose from a background of intestinal-type intraductal papillary mucinous neoplasms.

Cancer treatment involved surgery followed by adjuvant chemotherapy and radiotherapy (Fig. 1). Surgery was performed on August 2, 2012, involving a pancreaticoduodenectomy (Whipple procedure) and splenectomy with an end-to-end hepatojejunostomy, a side-to-side gastrojejunoscopy, and a side-to-side enterostomy. The surgery involved a 15-d hospital stay with no lasting pain or serious complications. The patient experienced occasional vomiting (approximately one to two times per week) after the surgery, which persisted throughout adjuvant treatment, and experienced a wound infection, which healed before the follow-up appointment 2 months after the operation. Adjuvant chemotherapy commenced 2 months after surgery, with one cycle of gemcitabine induction involving seven weekly treatments followed by two cycles of gemcitabine consolidation given by intravenous infusions of 1000 mg·m−2 administered for approximately 30 min (treatment plan: 7 wk on-treatment, 1 wk off-treatment, 3 wk on-treatment, 1 wk off-treatment, 3 wk on-treatment). The patient experienced anticipatory nausea and anxiety, which was managed with Maxolon and lorazepam (pro re nata). After a 2-wk break, the patient switched to a fluorouracil (5FU) regime involving continuous intravenous infusions of 225 mg·m−2·d−1 concurrent with radiotherapy. The 5FU cycle was initiated on the first day of radiotherapy and continued until the completion of radiotherapy (6 wk). Anticipatory nausea and anxiety continued throughout chemotherapy treatment. External beam radiotherapy involved 25 fractions administered daily (Monday to Friday) throughout February 2013. The dose point was the pancreas tumor bed with a total dose of 45 Gy (1.8 Gy per treatment) administered using an 18-MV photon dose per beam. The patient experienced nausea and fatigue after chemotherapy treatments as well as increased stress and anxiety, but no toxicities prevented adherence to the prescribed treatment regime (i.e., no dose adjustments or delays in treatment occurred). No radiotherapy-related toxicities were reported. The relative dose intensity of chemotherapy was 92% for gemcitabine (the final week of second maintenance cycle was cancelled by the medical oncologist to allow for a 2-wk break between chemotherapy and concurrent chemoradiotherapy regimes) and 100% for fluorouracil. The patient received 100% of the prescribed dose of radiotherapy. Adjuvant treatment was completed on February 19, 2013.

The patient was diagnosed with type 2 diabetes in 1999 and has required insulin since 2009. The patient has hyperlipidemia but was otherwise in good health. On enrolment into this trial, the patient’s medications included the following: Creon (25,000 U with meals, exocrine pancreatic insufficiency), Pantoprazole (40 mg·d−1, to prevent stomach irritation after Whipple surgery), NovoRapid (10, 10, and 12 U·d−1, diabetes), Lantus (26 U at night, diabetes), and Lipitor (40 mg·d−1; hyperlipidemia). The patient lost 13 kg since the Whipple surgery until baseline assessment (i.e., for a period of 2 months postsurgery). This protocol was approved by the human research ethics committee of the university, and the patient provided written informed consent.

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Exercise Intervention

The exercise intervention was commenced 3 months after surgery and was separate from specific physiotherapy exercise prescribed during in-patient visitations postsurgery. The exercise intervention involved twice weekly sessions of moderate- to high-intensity resistance and aerobic exercise for 6 months in an exercise clinic. In addition to baseline assessments, a thorough initial consultation was conducted with the patient to gather a comprehensive health and physical activity history to guide exercise prescription. The supervised exercise program commenced with two one-on-one sessions before participation within a group of 15 patients with various chronic disease diagnoses supervised by an accredited exercise physiologist. Each session commenced with a 5-min warm-up and finished with a 5-min cooldown involving light aerobic exercise and general flexibility exercises. The resistance exercise component of the program involved 10 standard exercises targeting the major muscle groups of the lower and upper body (leg press, leg extension, leg curl, calf raise, hip abduction and adduction, chest press, seated row, triceps extension, and bicep curl). The resistance exercise progressed in load from 12-repetition maximum (12RM) to 6RM, with two to four sets per exercise (16,30). To ensure the progressive nature of the program, the participant was encouraged to work past the specific RM prescribed, and if he exceeded the target, then additional resistance was added for the next set and/or session. The aerobic exercise component of the program involved 15–20 min of cardiovascular exercise, including walking and cycling. Intensity was set to 65%–80% of maximum heart rate, with an RPE between 11 and 13 (Borg 6–20 scale) (5,16,30). The patient was encouraged to supplement the clinic sessions with additional home-based aerobic exercise sessions involving walking and/or cycling, with the aim of accumulating a total of 150 min of aerobic exercise each week (30).

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Outcome Measures

Outcome measures were assessed at baseline, 3 months, and 6 months. The patient completed a familiarization session 4 d before baseline testing involving all physical function assessments. Resting blood pressure and heart rate were assessed at the beginning of the assessment session after resting in a supine position for 10 min.

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Physical capacity and functional ability

A series of standard tests were used to assess physical capacity and functional ability (16): 1) 400-m walk to evaluate aerobic capacity, 2) 1RM in the leg press to evaluate muscular strength, 3) repeated chair rise to evaluate muscular power (time taken to rise from a chair five times in a row), 4) stair climb to evaluate muscle power and ambulation (time taken to ascend a flight of stairs unassisted), 5) usual and fast pace 6-m walk to evaluate ambulation, 6) 6-m backward walk to evaluate dynamic balance, and 7) the sensory organization test performed on the Neurocom Smart Balancemaster (Neurocom, OR) to evaluate static balance. The tests were performed in triplicate (except for 400-m walk and 1RM), with sufficient rest between trials and the best performance on each test used in the analyses. Falls self-efficacy was also determined using the Activities-Specific Balance Confidence scale (ABC score; higher score represents greater balance confidence) (27).

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Body composition and bone mineral density

Whole body lean mass and fat mass were derived from whole body dual-energy x-ray absorptiometry (Hologic Discovery A, Waltham, MA). Appendicular lean mass, trunk adiposity, and visceral fat mass were assessed using standard procedures. Bone mineral density (BMD) of the hip and lumbar spine was also assessed using dual-energy x-ray absorptiometry.

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Physical activity levels

Self-reported physical activity was assessed by the leisure score index from the Godin Leisure-Time Exercise Questionnaire (17,22). The weekly duration of moderate and vigorous activity as well as resistance exercise were also reported.

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Patient reported outcomes

A series of questionnaires with sound psychometric properties were used to assess general health- and disease-specific quality of life, cancer-related fatigue, sleep quality, and psychological distress. The 36-item Short-Form Health Survey (SF-36) of the Medical Outcomes Study was used to assess general health-related quality of life status across the following domains: physical function, role physical, body pain, general health, vitality, social function, role emotional, and mental health (37). The utility index (SF-6D) obtained from the SF-36 was used to estimate monthly medical expenditure (6,15). The Functional Assessment of Cancer Therapy–Hepatobiliary (FACT-Hep) questionnaire was used to evaluate pancreatic cancer-specific quality of life across the domains: hepatobiliary symptoms, physical well-being, social/family well-being, emotional well-being, functional well-being, and total FACT-Hep score (20). Cancer-related fatigue was assessed using the Functional Assessment of Chronic Illness Therapy–Fatigue subscale (38). Sleep quality was determined using the Pittsburgh Sleep Quality Index (2). The Brief Symptom Inventory-18 was used to assess psychological distress across the domains of depression, anxiety, somatization, and global distress severity (40).

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No adverse events occurred during the exercise intervention. The patient completed a total of 35 of a possible 48 sessions during the 6-month intervention (73% attendance). Reasons for missed sessions centered on chemotherapy-related side effects (nausea and fatigue). He tolerated the exercise sessions well, completing the prescribed exercises during each session and progressing intensity and volume appropriately. Considerable improvements in all measures of physical capacity and functional ability were observed at 3- and 6-month assessment points ranging in magnitude from 2.5% to 42.1% (Table 1). Whole body and appendicular lean mass increased by 2.9%–8.2%, with increases in whole body and trunk fat mass also observed (1.5%–3%; Table 1). BMD remained relatively stable with −0.5% to 1.5% changes in hip and lumbar spine BMD (Table 1). Resting blood pressure and heart rate also remained relatively stable throughout the intervention (Table 1). Physical activity levels increased considerably, with a pronounced increase in the Godin leisure score index observed as well as the weekly minutes of moderate and vigorous aerobic exercise and resistance exercise (Table 1).

Pronounced improvements were observed in all of the patient reported outcomes at both 3- and 6-month assessment points (Table 2). Clinically meaningful improvements (i.e., ≥3 norm-based points) in SF-36 health-related quality of life domains were evident across all domains except for bodily pain. Substantial improvements in disease-specific quality of life were also reported, including a 13.0%–16.7% improvement in the hepatobiliary symptom subscale score. Reductions in cancer-related fatigue were significant and sleep quality improved between baseline and postintervention. Levels of psychological distress at baseline were associated with a classification of a clinically positive case of psychological distress (i.e., T-score ≥ 63). However, considerable reductions in psychological distress were also observed across depression, anxiety, and somatization domains, leading to a significant reduction in T-score to well below the clinical classification of distress. Furthermore, the predicted monthly medical expenditure decreased by 38%–51% between baseline and postintervention.

Anecdotally, the patient reported the following at the end of the 6-month exercise program: “I found it very beneficial,” “I feel stronger,” “I don’t feel as fatigued,” “Not everything becomes difficult,” “It’s helped clear my mind,” and “It’s helped me get my thinking straight.” He has continued with an ongoing supervised exercise program within the clinic beyond the formal 6-month intervention.

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This is the first examination of the safety and efficacy of a supervised exercise program in a pancreatic cancer patient. The primary finding of this case study was that exercise was well tolerated during adjuvant therapy for pancreatic cancer and resulted in clinically meaningful improvements in physical capacity and function, lean mass, physical activity levels, quality of life, cancer-related fatigue, and psychological distress. The case study identifies a novel therapy that may offer profound improvements in function and quality of life for people with pancreatic cancer—an exciting possibility especially considering the lack of progress in standard therapies for the past 30 yr (33).

Although it was not surprising to observe improvements across measurements of aerobic capacity, muscle strength, muscular power, ambulation, and balance after a well-designed exercise program, the magnitude of improvement in this type of clinical patient is highly noteworthy. It is important to note that this patient may not be representative of all pancreatic cancer patients, but he was able to comply with the training program while undergoing difficult adjuvant treatments and reach exercise intensities and volumes required to elicit physiological adaptation. The ability to improve physical capacity and function during a time in which these outcomes are expected to decline is an important clinical finding. In addition, the 3%–8% increase in lean mass observed has a high degree of clinical relevance given the rapid weight loss common after pancreatic surgery and the potential consequences of reduced lean mass associated with cancer cachexia (i.e., sarcopenia, frailty, and compromised functional ability [35]). These findings are especially relevant given the patient was recovering from major surgery and undergoing intensive chemotherapy and radiotherapy treatments. Indeed, it may well be that the physiological improvements prompted by exercise help patients better tolerate the intensive adjuvant therapies required for the treatment of pancreatic cancer and mitigate treatment toxicities (10). Furthermore, the exercise intervention prompted favorable changes in physical activity levels, such that the patient progressed from a sedentary lifestyle to meeting international physical activity guidelines.

Given the poor prognosis associated with pancreatic cancer, therapies that increase quality of life in these patients are of great clinical importance. In this case study, we observed improvements across all domains of general health and disease-specific quality of life (except bodily pain) of magnitudes well in excess of clinically meaningful levels (i.e., > 3 NBS points for the SF-36 [4,36]). Notably, these improvements were observed despite the patient undergoing intensive chemotherapy and radiotherapy during the first 4 months of the exercise program. Quality of life, as assessed by the physical and mental health composite scores of the SF-36, has been previously reported to decrease by 16% and 13%, respectively, from pre-Whipple surgery to 3 months postoperation (3). Moreover, a further 12% and 4% decrease in physical and mental composite scores have been reported between 3 and 24 months post-Whipple surgery (3), highlighting the continued negative decline in quality of life expected for pancreatic patients with resectable disease. In this case study, we observed physical and mental composite scores to improve by 24%–35% and 43%–69%, respectively, throughout the exercise intervention (which commenced 3 months post-Whipple surgery and finished 9 months postsurgery). Clearly, the magnitude of improvements elicited by the exercise intervention was quite remarkable in contrast to the expected continued decline postsurgery. Importantly, the hepatobiliary symptom domain improved by 13%–17% during the exercise program, suggesting that exercise may attenuate symptoms specific to patients with pancreatic cancer in addition to general health quality of life domains.

Cancer-related fatigue is the most commonly reported adverse side effect of cancer treatment and is estimated to affect between 80% and 90% of patients receiving chemotherapy or radiotherapy (1,13,32). The persistent tiredness associated with cancer-related fatigue is experienced during and after treatment and has a significant negative impact on quality of life (12,19). Although the precise mechanisms associated with cancer-related fatigue have yet to be identified, the driving factors are commonly theorized to be associated with negative physiological (i.e., cardiorespiratory fitness, muscle strength, and body composition), biologic/hematologic (i.e., inflammatory response and metabolic/endocrine/immune function), psychological (i.e., anxiety, depression, and distress), behavioral (i.e., sleep quality and quantity, and appetite), and social (i.e., social interaction) changes resulting from cancer and its treatment (25). Despite undergoing chemotherapy and radiotherapy throughout the exercise intervention, the pancreatic cancer patient in this case study displayed pronounced reductions in fatigue at 3 months (4.5-fold improvement) and 6 months (5.9-fold improvement). This was reflected by the improvements observed in the vitality domain of the SF-36, which were the greatest of all domains assessed (60%–160%). Notably, the exercise program elicited positive adaptations in many of the factors believed to be associated with cancer-related fatigue (25). This initial evidence suggests that exercise may offer a potent stimulus to counteract fatigue in pancreatic cancer patients during and after adjuvant therapy.

In comparison with other cancer patients, pancreatic cancer patients display significantly higher rates of psychological distress and the highest reported levels of depression and anxiety (8,39). Although not entirely surprising given the poor prognosis and intensive treatments associated with a diagnosis of pancreatic cancer, this is a critical issue that needs to be addressed through effective supportive care interventions. Appropriate exercise prescription has been demonstrated to alleviate psychological distress in patients with other cancer diagnoses (11). At study entry, the patient in this case study had a level of psychological distress associated with classification of a clinically positive case of psychological distress (i.e., T-score ≥ 63) (14). Throughout the supervised exercise intervention, significant improvements in depression, anxiety, and somatization were observed (33%–100%), despite continuing adjuvant treatment. At the completion of the 6-month supervised exercise program, the patient reported no distress across any of the domains. Importantly, the patient did not receive any psychological counseling, supportive care services, or medication to relieve his distress. However, involvement in the supervised exercise program may have improved the patient’s social support network, which could have contributed to the observed improvements in psychological distress. Well-designed randomized controlled trials are required to examine the effect of exercise interventions on psychological distress in this patient population but these results highlight the promise of a supervised exercise intervention as a potentially effective adjunct therapy to manage the pronounced psychological distress associated with pancreatic cancer.

Inherent to this case study is the limitation of involving a single individual. It is possible that this patient was a high responder to exercise, and the same magnitude of benefit may not be apparent among all pancreatic cancer patients, especially those with more advanced disease. Randomized controlled trials are needed to determine whether the scope and magnitude of improvements can be reproduced consistently in pancreatic cancer patients. Furthermore, future trials should explore the role of nutritional support in addition to targeted exercise prescription to counteract cachexia and to optimize the gains in muscle mass as well as compare the efficacy of various exercise modalities, intensities, duration, and timing of exercise to determine what regimens are most effective for pancreatic cancer patients.

In conclusion, this case study is unique as it involves the first empirical examination of a supervised resistance and aerobic exercise program in a pancreatic cancer patient undergoing active treatment. Given the scope and magnitude of improvements observed, the application of exercise as a critical component of the multidisciplinary management of pancreatic cancer may be warranted to enhance function and quality of life. This is an exciting possibility given the lack of success in progressing medical therapies for pancreatic cancer for the last 30 yr. Indeed, this initial case study identifies an important area for future clinical trials—research that may prompt a paradigm shift in the treatment of pancreatic cancer.

The authors would like to thank the patient for participating in this case study. PC was supported by the Cancer Council Western Australia Postdoctoral Research Fellowship. DAG was funded by a Movember New Directions Development Award obtained through the Prostate Cancer Foundation of Australia’s Research Program. The results of the present study do not constitute endorsement by the American College of Sports Medicine.

The authors have no conflicts of interest to disclose.

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