Med Oncol (2015) 32:114 DOI 10.1007/s12032-015-0563-5

ORIGINAL PAPER

Comprehensive geriatric assessment and traditional Chinese medicine intervention benefit symptom control in elderly patients with advanced non-small cell lung cancer Dong Xue1 • Shuyan Han2 • Shantong Jiang2 • Hong Sun1 • Yanzhi Chen1 Yuanqing Li1 • Wei Wang1 • Ye Feng1 • Ke Wang1 • Pingping Li1



Received: 1 March 2015 / Accepted: 4 March 2015 / Published online: 15 March 2015 Ó Springer Science+Business Media New York 2015

Abstract The aim of this study was to observe the symptom improvement and clinical benefit in elderly patients with advanced non-small cell lung cancer (NSCLC) stratified on the basis of CGA findings after treatment with a combination of traditional Chinese medicine and Western medicine. Twenty-four elderly advanced NSCLC patients with a mean age of 73.0 ± 5.3 (65–83) years were categorized into three stratifications according to CGA results, namely function independent, mildly function impaired, and function dependent. They received standardized therapy, individualized therapy, and best supportive care, respectively. The patients receiving standardized therapy and individualized therapy were randomized into two groups, with or without traditional Chinese medicine for symptom control, while for all the patients receiving best supportive care, traditional Chinese medicine was administered. Nine non-elderly NSCLC patients (\65 years old) were enrolled as control and treated in accordance with NCCN NSCLC treatment

guidelines. EORTC QLQ-C30 core scale, LC13 scale, and MDASI–TCM scale were used to assess relevant symptoms before and after treatment. After treatment for 3 weeks, it was shown by QLQ-C30?LC13 scales, for function-dependent patients, that the physical and role performances and the global health status were improved and the symptoms of fatigue and cough were alleviated; by MDASI–TCM scale, the symptoms of fatigue, cough, and expectoration were improved. In function-independent and mildly function-impaired elderly patients, there were no significant changes in functional status and symptoms. But in non-elderly patients, the physical and social performances were lowered, and the symptoms of fatigue, constipation, and poor appetite were aggravated. The elderly patients with advanced NSCLC were categorized on the basis of CGA findings, and traditional Chinese medicine may be beneficial to symptom control of function-dependent patients. Keywords Elderly patient  Advanced lung cancer  Comprehensive geriatric assessment  Clinical benefit  Quality of life  Symptom control

& Pingping Li [email protected] Dong Xue [email protected] 1

2

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Fucheng Road No. 52, Haidian District, Beijing 100142, China Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Integration of Chinese and Western Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China

Abbreviations NSCLC CGA NCCN EORTC QLQ-C30 core scale LC13 scale MDASI–TCM scale

Non-small cell lung cancer Comprehensive geriatric assessment National Comprehensive Cancer Network European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 scale Lung Cancer 13 scale M.D. Anderson Symptom Inventory–Traditional Chinese Medicine scale

123

114 Page 2 of 7

Med Oncol (2015) 32:114

Introduction

Cancer Hospital, from August 2012 to March 2013 were selected for this study. Inclusion criteria comprised:  histopathologically confirmed advanced NSCLC; ` American Joint Committee on Cancer (AJCC) stage IIIBIV; ´ C65 years old; ˆ capable of reading and understanding the questionnaires; and ˜ informed consent. Exclusion criteria comprised:  unable to understand the questionnaires; ` unwilling to participate in this study; and ´ unable to complete the research.

Cancer incidence is much higher in population over the age of 65 years than in younger ones. The special management of elderly patients with cancer has become a worldwide public health concern because of the aging of population. The heterogeneity of elderly population is reflected in multiple and different factors, such as comorbidity, physical function, and psychological status, which may influence the final outcome of cancer treatment and largely explain the difficulty in establishing management recommendations [1]. Comprehensive geriatric assessment (CGA) is a systematic approach aiming to assess physical function, comorbidity, nutritional status, polypharmacy, cognition, emotional status, and social support in elderly patients. A number of studies demonstrated that individualized geriatric intervention plans guided by CGA had positive effects on physical and functional status and mortality and recommended the introduction of CGA as a routine assessment in elderly patients with cancer [2–5]. Lung cancer is the most common fatal cancer in males and females and accounts for 29 % of all male and 26 % of all female cancer-related mortalities [6]. The incidence of lung cancer increases with age, and more than half of patients are older than 65 years. However, the elderly patients with lung cancer remain understudied as compared to younger patients. Multidisciplinary intervention has been investigated. In China, traditional Chinese medicine has played a unique role in comprehensive therapy of lung cancer. It has been proven that the administration of traditional Chinese medicine is beneficial to improving immunity and physical function, reducing side effects associated with chemo- and radiotherapy, decreasing symptom distress, and increasing quality of life (QoL). The integrated Chinese-Western therapy can significantly improve the survival and symptoms of patients with advanced NSCLC compared with chemotherapy alone [7, 8]. In the present study, advanced NSCLC patients aged C65 years were categorized on the basis of CGA findings and treated with a combination of traditional Chinese medicine and Western medicine so as to investigate the symptom improvement and clinical benefit of these patients.

Patients and methods Patients Patients hospitalized in the Department of Integrative Medicine and Geriatric Oncology, Peking University

123

Stratification criteria CGA was carried out in eligible patients by experienced physicians. On the basis of CGA results, the patients were categorized into:  function independent: without instrumental activities of daily life (IADL) dependence and activities of daily life (ADL) dependence, and with good nutritional status; ` mildly function impaired: with at least one item of IADL dependence, without ADL dependence, and at risk of malnutrition; and ´ function dependent: C85 years old, with at least one item of ADL dependence, and with malnutrition. Treatment regimen By reference to National Comprehensive Cancer Network (NCCN) guidelines for senior adult oncology, the functionindependent, mildly function-impaired, and function-dependent patients received standardized therapy, individualized therapy, and best supportive care, respectively. Furthermore, the patients receiving standardized therapy and individualized therapy were randomized into two groups, respectively, with or without traditional Chinese medicine including decoctions and patent medicines for symptom control, while for all the patients receiving best supportive care, traditional Chinese medicine was administered. Decoctions 150 mL should be orally taken on an empty stomach twice daily (every 12 h), and the patent medicines should be taken according to the manufacturer’s package insert. Outcome assessments The primary endpoint of the study was QoL [trial outcome index (TOI)], and the secondary endpoints included overall survival (OS), median survival time (MST), CGA, WHO, or Response Evaluation Criteria in Solid Tumors (RECIST). For standardized and individualized therapy groups, the QoL and symptoms were assessed on baseline (day 1 prior to chemotherapy), and day 7, day 21, day 42, and day 63 after chemotherapy, while for the best supportive care group, on baseline, and day 21, day 42, and day 63 after chemotherapy.

Med Oncol (2015) 32:114

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale, Lung Cancer 13 (LC13) scale, and M.D. Anderson Symptom Inventory–Traditional Chinese Medicine (MDASI–TCM) scale were used to assess relevant symptoms before and after treatment. The evaluation was carried out by an independent evaluator who was blinded to the intervention. The questionnaire of EORTC QLQ-C30?LC13 is composed of a total of 43 items, including items evaluating functioning domains, symptom scales and single items assessing common physical symptoms of cancer, and items of global health. All scales range in a transformed score of 0–100. High functioning and global scale scores and low symptom scores reflect better QoL. The MDASI–TCM scale is composed of 13 core MDASI symptom items and 10 TCM symptom items and has adequate reliability with a Cronbach’s a value of 0.9. The questionnaire of MDASI–TCM comprises two parts, one of which is evaluation of 23 symptom items with scores from 0 (no symptom) to 10 (worst imaginably) and the other is evaluation of six symptom interference items with scores from 0 (no interference) to 10 (complete interference). High scores indicate more severe symptoms and worse QoL. Statistical analysis The statistical analyses of EORTC QLQ-C30, LC13, and MDASI–TCM scales were carried out according to scale manuals. Data were expressed as x  s. All statistical analyses were performed with SPSS statistical software, version 19.0 (SPSS Inc., Chicago, IL, USA). The statistic difference chart was determined using Prism GraphPad Software, version 5.01(GraphPad Inc., San Diego, CA, USA). One-way analysis of variance (ANOVA) and Wilcoxon rank-sum test were used in intergroup comparisons, and paired t test and paired Wilcoxon rank-sum test were used in intragroup comparisons before and after the treatment. P \ 0.05 was considered statistically significant.

Page 3 of 7 114

vinorelbine, or gemcitabine alone or in combination with platinum-based drug. In the same time, nine non-elderly NSCLC patients aged 56.2 ± 4.8 (46–62) years were enrolled for control and had received 38 cycles of chemotherapy in all (mean 4.2 cycles), including paclitaxel, pemetrexed, vinorelbine, or gemcitabine in combination with platinum-based drug. The baseline characteristics of the elderly and non-elderly patients are summarized in Tables 1 and 2, respectively. Stratification and treatment Guided by CGA, the 24 elderly advanced NSCLC patients were categorized into three stratifications, namely function independent (10), mildly function impaired (6), and function dependent (8), as shown in Table 3. Eastern Cooperative Oncology Group performance status (ECOG PS) of patients in different stratifications As shown in Table 4, the ECOG PS rating results were different from the stratifications guided by CGA. For mildly function-impaired elderly patients, individualized therapy, including low-dose chemotherapy and target therapy, should be administered according to NCCN guidelines for senior adult oncology, but by reference to NCCN guidelines for NSCLC, the treatment principles for elderly and non-elderly patients with PS B 2 were similar. For function-dependent patients, palliative therapy should be used according to NCCN guidelines for senior adult oncology, but for the five patients with PS B 2, the treatment principle should be similar to that of non-elderly patients.

Table 1 Characteristics of elderly advanced NSCLC patients All patients (n = 24) Mean age, years (range)

73.0 ± 5.30 (65–83)

Parameter

N

%

Male

13

54.2

Female

11

45.8

8

33.3

16

66.7

Sex

Results Patients’ characteristics A total of 24 elderly patients with histopathologically confirmed advanced NSCLC, including 13 (54.2 %) males and 11 (45.8 %) females, were enrolled in this study, and the mean age was 73.0 ± 5.3 (range 65–83) years. These patients had received 65 cycles of chemotherapy in all (mean 2.7 cycles), including paclitaxel, pemetrexed,

AJCC Stage IIIB IV Histological type Adenocarcinoma

13

54.2

Squamous cell carcinoma

9

37.5

Other

2

8.3

123

114 Page 4 of 7

Med Oncol (2015) 32:114

EORTC QLQ-C301LC13 scales

MDASI–TCM scale

There was no significant difference between function-independent and mildly function-impaired elderly patients in functioning scale and global health scale, but in functiondependent patients, the physical and social performances and the global health status were significantly lowered (P \ 0.05; Fig. 1a). The cognitive and social performances of non-elderly patients were significantly better than those of elderly patients (P \ 0.05; Fig. 1b), and the symptoms of fatigue, cough, dyspnea, appetite loss, and insomnia in elderly patients were obvious. There were no significant changes in the items of functioning scale for function-independent and mildly function-impaired elderly patients, but for functiondependent patients, the physical and role performances and the global health status were improved. In non-elderly patients, the scores of emotional and social performances were reduced, indicating that these performances were lowered. There were no significant changes in the items of symptom scale for function-independent and mildly function-impaired elderly patients, but for function-dependent patients, the scores of fatigue and cough were reduced, indicating that these symptoms were alleviated. In nonelderly patients, the scores of fatigue and constipation were increased, indicating that these symptoms were aggravated.

In all the patients, the scores of fatigue, cough, expectoration, sweating, and dysphoria were the highest, particularly in the function-dependent elderly patients. Emotion was the most obvious interference item, and there was no significant difference among the elderly patients in three stratifications, but the score of the non-elderly patients was higher than that of elderly patients.

Table 2 Characteristics of non-elderly advanced NSCLC patients All patients (n = 9) Mean age, years (range)

56.2 ± 4.8 (46–62)

Parameter

N

%

6

66.7

3

33.3

IIIB

4

44.4

IV

5

55.6

Adenocarcinoma

5

55.6

Squamous cell carcinoma

4

44.4

MDASI–TCM scores In all the patients, the scores of fatigue, cough, expectoration, sweating, and poor appetite were the highest. In function-dependent elderly patients, the scores of fatigue, cough, and expectoration were reduced, indicating these symptoms were alleviated. In function-independent and mildly function-impaired elderly patients, there were no significant changes in symptom scores. In non-elderly patients, the scores of fatigue, sleep disturbance, and poor appetite were increased than before, indicating these symptoms were aggravated.

Discussion In China, lung cancer is the most frequently diagnosed cancers in males (22.14 %) and is the leading cause of cancer death in both males (27.21 %) and females (21.91 %) [9]. The prognosis of lung cancer remains poor. Up to 85 % of patients are diagnosed at an advanced stage. Most newly diagnosed cancer and cancer deaths occur in

Sex Male Female AJCC Stage

Table 4 ECOG PS of patients in different CGA stratifications CGA stratifications

Histological type

The number of cases 0–1

2

[2

Function independent

7

3

0

Mildly function impaired

3

2

1

Function dependent

1

4

3

PS:

Table 3 Stratification guided by CGA Stratification Function independent Mildly function impaired Function dependent

Group

The number of cases

ADL dependent

IADL dependent

ST

6

0

0

26.0 ± 1.4

ST ? TCM

4

0

0

26.0 ± 0.8

IT

3

0

1

18.7 ± 1.2

IT ? TCM

3

0

2

19.3 ± 0.6

BSC ? TCM

8

4

7

15.0 ± 1.1

ST standardized therapy, IT individualized therapy, TCM traditional Chinese medicine, BSC best supportive care

123

Nutrition assessment

Med Oncol (2015) 32:114

Page 5 of 7 114

Fig. 1 Baseline scores of QLQC30?LC13 scales (0–100). In function-dependent patients, the physical and social performances and the global health status were significantly lower than patients in functionindependent and mildly function-impaired groups (*P \ 0.05) (a). The cognitive and social performances of nonelderly patients were significantly better than those of elderly patients (*P \ 0.05) (b)

patients over the age of 65 years. Even if elderly patients have physiological and pathological features different from younger patients, which are essential in directing their therapeutic decisions, it has been shown that age is not a significant prognostic factor for overall survival and response to treatment for patients with either type of lung cancers and should not be criteria of choice for treatment. The elderly patients may be as likely to tolerate and benefit from the same treatment options for NSCLC as younger patients, with manageable side effects [10–12]. The selection of treatment regimens is restricted by functional status, comorbidity, disease stage, etc., of the elderly patients, and the treatment outcomes should be measured not only by survival, but also by functional status and QoL [2, 13]. The CGA, which is defined as a multidisciplinary evaluation capable of revealing problems limiting treatment that are not detected by routine examinations, has been used in many cancer centers in both developed and developing countries. Kanesvaran et al. [14] has retrospectively analyzed the impact of all domains of CGA on overall survival, confirmed the importance of CGA in assessment of elderly patients with cancer, and developed a prognostic scoring system for elderly patients with cancer. Chaı¨bi et al. [15] has found that CGA did significantly influence treatment decisions in 82 % of older cancer

patients. Utilization of a CGA to evaluate the comprehensive health status of patients before decision-making can help physicians make the optimal treatment regimens so as to obtain satisfactory clinical benefits, reduce toxicity and side effects related to treatment, and improve QoL. Caillet et al. [1] has revealed that functional status assessed by the ADL score and malnutrition was independently associated with changes in planned cancer treatment. It also has been shown that administration of a CGA combined with targeted/individual intervention and care plans as a result of findings on the CGA resulted in improved symptoms among elderly cancer patients, including improved pain control, decreased depression rates, and increased well-being [16]. These benefits would be particularly useful in elderly patients with NSCLC, in whom the control of symptoms associated with cancer and other comorbidities is of primary importance regardless of goal and modality of therapy, and inadequate symptom control will not only produce suffering but may have an adverse effect on the course of illness [2, 10]. It has been proven that traditional Chinese medicine has a unique advantage in symptom control. In this study, a total of 24 elderly patients with histopathologically confirmed advanced NSCLC were categorized into three stratifications on the basis of CGA findings, namely function independent, mildly function impaired, and function

123

114 Page 6 of 7

dependent and received standardized therapy, individualized therapy, and best supportive care, respectively. The patients receiving standardized therapy and individualized therapy were randomized into two groups, respectively, with or without traditional Chinese medicine for symptom control according to the questionnaire results, while for all the patients receiving best supportive care, traditional Chinese medicine for symptom control was administered in consideration of ethics. We found that fatigue is the most common symptom for both elderly and non-elderly patients. After intervention with traditional Chinese medicine, in function-dependent elderly patients, the symptoms of fatigue, cough, and expectoration were alleviated obviously, and the global health status was improved, as shown in QLQ-C30, LC13, and MDASI–TCM scales. But in nonelderly patients, the symptoms of fatigue, constipation, and poor appetite were aggravated, which may be associated with the standardized therapy including chemotherapy and radiotherapy. The function-independent and mildly function-impaired patients were randomized into two groups, respectively, but the intergroup comparisons were not made due to the small sample size. Thus, the role of traditional Chinese medicine in symptom control for functionindependent and mildly function-impaired patients still need further investigation. In younger patients, ECOG PS can provide a useful guide in making treatment decisions and is a major prognostic factor of therapeutic responses, toxicities, and outcomes. However, PS is likely affected by heterogeneity of elderly adults and is often insufficient to assess the overall status of elderly cancer patients, in whom chronic illnesses, polypharmacy, depression, malnutrition and dementia are more common and possibly underestimated. These situations may cause false interpretation of PS [2, 12, 17]. One of our previous studies (data not shown) revealed that PS as the primary factor of decision-making for elderly cancer patients could not reflect patients’ comprehensive status, and therefore, planned treatment regimen could not be accomplished. Comorbidity was one important factor associated with treatment regimen changes. In the present study, the stratifications guided by CGA are different from traditional PS rating results. CGA can provide more important and comprehensive information to help physicians develop the optimal treatment plans beneficial to elderly cancer patients. Although, in many studies, CGA has been advocated as the gold standard for evaluation of elderly patients, the adoption of CGA in oncology practice is not widespread because of the difficulties with feasibility, practicability, objectivity, and cost and limited consensus regarding methodology [18, 19]. This study included the core items of CGA mainly focusing on functional and nutritional status,

123

Med Oncol (2015) 32:114

and further investigations on comorbidity, polypharmacy, and psychological status are still needed. In conclusion, the elderly patients with advanced NSCLC were categorized on the basis of CGA findings, and the administration of traditional Chinese medicine can improve the symptoms of function-dependent patients, such as fatigue and cough. But for the function-independent and mildly function-impaired patients, clinical benefits need to be further investigated. Conflict of interest

None.

Compliance with Ethical Standards This study is a research involving human participants and was approved by the Ethic Committee of Peking University Cancer Hospital, and written informed consent of all patients was obtained.

References 1. Caillet P, Canoui-Poitrine F, Vouriot J, Berle M, Reinald N, Krypciak S, et al. Comprehensive geriatric assessment in the decision-making process in elderly patients with cancer. ELCAPA study. J Clin Oncol. 2011;29:3636–42. 2. Chen CC, Kenefick AL, Tang ST, McCorkle R. Utilization of comprehensive geriatric assessment in cancer patients. Crit Rev Oncol Hematol. 2004;49:53–67. 3. Kristjansson SR, Nesbakken A, Jordhøy MS, Skovlund E, Audisio RA, Johannessen HO, et al. Comprehensive geriatric assessment can predict complications in elderly patients after elective surgery for colorectal cancer: a prospective observational cohort study. Crit Rev Oncol Hematol. 2010;76:208–17. 4. Extermann M, Aapro M, Bernabei R, Cohen HJ, Droz JP, Lichtman S, et al. Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol. 2005;55:241–52. 5. Kim KI, Park KH, Koo KH, Han HS, Kim CH. Comprehensive geriatric assessment can predict postoperative morbidity and mortality in elderly patients undergoing elective surgery. Arch Gerontol Geriatr. 2013;56:507–12. 6. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300. 7. Lin G, Li Y, Chen S, Jiang H. Integrated Chinese-western therapy versus western therapy alone on survival rate in patients with non-small-cell lung cancer at middle-late stage. J Tradit Chin Med. 2013;33:433–8. 8. You J, Shan MJ, Zhao H. Clinical study of integrative treatment for ninety-one elderly patients with advanced non-small cell lung cancer. Zhongguo Zhong Xi Yi Jie He Za Zhi (Chin). 2012;32: 774–8. 9. Chen W, Zheng R, Zhang S, Zhao P, Li G, Wu L, et al. Report of incidence and mortality in China cancer registries, 2009. Chin J Cancer Res. 2013;25:10–21. 10. VanderWalde A, Pal SK, Reckamp KL. Management of nonsmall-cell lung cancer in the older adult. Maturitas. 2011;68: 311–21. 11. Hurria A, Kris MG. Management of lung cancer in older adults. CA Cancer J Clin. 2003;53:325–41. 12. Tas F, Ciftci R, Kilic L, Karabulut S. Age is a prognostic factor affecting survival in lung cancer patients. Oncol Lett. 2013;6: 1507–13.

Med Oncol (2015) 32:114 13. Pal SK, Hurria A. Impact of age, sex, and comorbidity on cancer therapy and disease progression. J Clin Oncol. 2010;28:4086–93. 14. Kanesvaran R, Li H, Koo KN, Poon D. Analysis of prognostic factors of comprehensive geriatric assessment and development of a clinical scoring system in elderly Asian patients with cancer. J Clin Oncol. 2011;29:3620–7. 15. Chaı¨bi P, Magne´ N, Breton S, Chebib A, Watson S, Duron JJ, et al. Influence of geriatric consultation with comprehensive geriatric assessment on final therapeutic decision in elderly cancer patients. Crit Rev Oncol Hematol. 2011;79:302–7. 16. Rao AV, Hsieh F, Feussner JR, Cohen HJ. Geriatric evaluation and management units in the care of the frail elderly cancer patient. J Gerontol A Biol Sci Med Sci. 2005;60:798–803.

Page 7 of 7 114 17. Extermann M, Chen H, Cantor AB, Corcoran MB, Meyer J, Grendys E, et al. Predictors of tolerance to chemotherapy in older cancer patients: a prospective pilot study. Eur J Cancer. 2002; 38:1466–73. 18. Parks RM, Lakshmanan R, Winterbottom L, Al Morgan D, Cox K, Cheung KL. Comprehensive geriatric assessment for older women with early breast cancer—a systematic review of literature. World J Surg Oncol. 2012;10:88. 19. Ruiz M, Reske T, Cefalu C, Estrada J. Management of elderly and frail elderly cancer patients: the importance of comprehensive geriatrics assessment and the need for guidelines. Am J Med Sci. 2013;346:66–9.

123

Comprehensive geriatric assessment and traditional Chinese medicine intervention benefit symptom control in elderly patients with advanced non-small cell lung cancer.

The aim of this study was to observe the symptom improvement and clinical benefit in elderly patients with advanced non-small cell lung cancer (NSCLC)...
247KB Sizes 0 Downloads 5 Views