Editor-in-Chief Hatice Kübra Elçioğlu Vice Editors Levent Kabasakal Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Journal of Research in Pharmacy 2013 , Vol 17 , Num 2
Quality of life assessment of patients with metastatic lung cancer receiving platinum-based chemotherapy
Beril G. Kıvrak-Bernardelli3, Çağlar Macit1, S. Beril Kadıoğlu1, Taflan Salepci2, Philip M. Clark1
1Yeditepe University, Clinical Pharmacy, Istanbul, Turkey
2Ministry of Health Dr. Lutfi Kirdar Research and Training Hospital, Oncology, Istanbul, Turkey
3University of Maryland, School of Medicine, Baltimore, USA
DOI : 10.12991/201317380


AMAÇ: Bu çalışmanın amacı, kemoterapi sırasında yaşam kalitesinde olması muhtemel değişiklikler, yaşam kalitesini etkileyen faktörler ve performans durumuyla yaşam kalitesi arasındaki ilişkiyi incelemektir.

MATERYAL ve METOTLAR: Bu çalışma Dr. Lütfü Kırdar Kartal Eğitim ve Artaştırma Hastanesi onkoloji kliniklerinde yürütülmüştür. İleri düzeyde küçük hücreli akciğer kanseri ve faz IV(metastatik) küçük hücreli olmayan akciğer kanseri teşhisi alan hastalar çalışma kapsamına alınmıştır. Hastalara platin içeren kemoterapi uygulanmıştır. Hastaların yaşam kalitesini ölçen QOL (Quality of Life) EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire/Avrupa Kanser Araştırmaları ve Tedavi Organizasyonu Yaşam Kalitesi Anketi) (versiyon 3.0) ve akciğer kanseri modülü QLQ-LC13 (Quality of Life Questionanaire Lung Cancer) dört kez yürütülmüştür. Hastaların klinik ve performans durum {Karnofsky Performance Status Scale (KPS) ve Eastern Cooperative Oncology Group/Doğu Kooperatif Onkoloji Grubu (ECOG)} verileri çalışma süresince kaydedilmiştir.

BULGULAR: Tedaviyle birlikte, kemoterapiye bağlı yan etkiler ile advers ilaç reaksiyonları ve hastalığın ilerlemesiyle ilgili semptomlarda anlamlı artışlar kaydedilmiştir. Hem ECOG performans ile EORTC QLQ-C30 tüm alanlarında (r=-0.74, p<0.05), hem de KPS ve EORTC QLQ-C30 arasındaki (r= -0.71, p<0.05), güçlü, anlamlı ve nagatif korelasyon gözlenmiştir.

SONUÇLAR: Bu çalışma metastatik akciğer kanserinde platin içeren kemoterapi alan hastalarda yaşam kalitesi açısından fayda göremedikleri gözlenmiştir. Bu hasta popülasyonunda yaşam kalitesi rutin olarak değerlendirildiği takdirde, kemoterapi yan etkilerini en aza indirilmiş tedavi programlarının geliştirilmesi ve hastaların iyi halinin maksimum düzeye çıkarılması konusunda teşvik edilebilir.


Epidemiology and mortality
Lung cancer has become one of the leading global causes of cancer death in both men and woman[1], and is responsible for 12.8% of all cancer cases and 17.8% of the all cancer deaths[2]. The 5-year relative survival rate for lung cancer for the period of 1996 to 2003 was 16%, reflecting only a modest improvement from the 1950s[3-6]. In Turkey, lung cancer incidence is increasing by 3% annually[7,8]; with a male prepondrance (m/f ratio12:1). The most commonly diagnosed histological types are epidermoid carcinoma in males and adenocarcinoma in females[9].

Approximately 85% of patients with lung cancer are diagnosed at an advanced stage that is not amenable to surgical intervention. For patients with stage metastatic non small cell lung carcinoma (NSCLC) or extensive-stage small cell lung carcinoma (SCLC) the 5 year survival rate may be less than 1%[10].

Morbidity related to lung carcinomas
Besides high mortality, lung cancer is associated with high morbidity (see Appendix 1) including chest pain, cough, hemoptysis and dyspnea.[11,12]. Cough may be due to airway obstruction, post obstructive pneumonia, excessive mucus production, parenchymal metastases, or pleural effusion[13]. Dyspnea occurs in most patients with lung cancer during the course of their disease due to direct impingement of the airway, underlying chronic lung disease, radiation- or chemotherapy- induced pneumonitis, infection, pleural effusion, or pulmonary embolism[14].

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APPENDIX 1: Lung cancer symptoms according to tumor invasion[15]

The commonest sites of metastases are contra-lateral lung, brain, liver, bone, adrenal gland, and extra-thoracic lymph nodes. Symptoms of brain metastases may include headache, nausea, vomiting, focal weakness, seizures, confusion, ataxia, and visual disturbances[15]. In terms of bone metastasis, the axial skeleton and proximal long bones are most commonly involved. Pain due to bone metastases is present in up to 25% of patients at initial diagnosis.[16].

Constitutional symptoms, such as depression, fatigue, anxiety, insomnia, anorexia, and cachexia, cause significant debility in patients with lung cancer. Depression and psychological distress are very common, but are infrequently recognized or treated[17].

Less frequently encountered, paraneoplastic syndromes describe the effects of cancer that occur systemically or at sites distant from tumor such as symptoms related to hypercalcemia[18], hyponatremia[19], Cushing’s syndrome[20], Lambert- Eaton syndrome, and other neurologic disorders.

Treatment of advanced lung cancer
The cornerstone of treatment of patients with extensive stage SCLC is multiagent chemotherapy. Stage IV non-small cell lung cancer (NSCLC) is largely incurable using present-day therapies. For most patients under age 75 years with good performance status, the best first approach is double-agent chemotherapy utilizing carboplatin plus a second agent, usually paclitaxel, gemcitabine, or docetaksel[21] (see Appendix 2).

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APPENDIX 2: Stage IV nsclc common treatment[21]

It has been surmised that patients who have an ECOG performance status of 0 or 1 may benefit more than patients with performance status 2, from the combination of a platinum agent, either cisplatin or carboplatin, and a second agent[22].

Quality of life assessment in lung cancer
Quality of life (QOL) can be defined as the effect of an illness and its therapy upon a patient’s physical, psychological, and social well being as perceived by the patient themselves[23]. QOL assessments should be given due priority whenever it is expected that the survival differences between the treatment groups is going to be small, or when the difference in at least one factor predicting QOL is expected to be large. The effect of two different therapeutic modalities on QOL and overall survival helps select the better modality. In fact, a particular treatment may be preferred if it improves the QOL, even if the survival is not superior[24].

QOL is closely linked to symptom burden and severity in lung cancer. Loss of physical functioning, psychological events such as depression, and reduced overall QOL are associated with uncontrolled symptoms[25,26]. In addition, depression has been found to be an independent prognostic factor for lung cancer, irrespective of stage[27].

The European organization for the treatment and research of cancer quality of life questionnaire, EORTC QLQ-C30, (see Appendix 3) includes five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea, and vomiting), and one global health and QOL scale. This instrument has demonstrated a high reliability and validity across the continents[28]. The EORTC QLQ-LC 13 questionnaire (see Appendix 4) was developed as a lung cancer specific supplementary to the EORTC QLQ-C30. It assesses lung cancer related symptoms, treatment related side-effects, pain, and pain medication[29]. The Turkish language versions of both EORTC QLQ-C30 and QLQ-LC13 have been validated for use in lung cancer patients.[30,31]

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APPENDIX 3: EORTC QLQ C-30 questionnaire (English)

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APPENDIX 3: EORTC QLQ C-30 questionnaire (English)

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AP PENDIX 4: EORTC QLQ LC-13 questionnaire (English)

Performance status (PS)
PS is the patient’s ability to perform certain physical activities, especially related to mobility, work, and self-care. The most well established tools are the Karnofsky Performance Scale (KPS) (see Appendix 5), and the Eastern Cooperative Oncology Group (ECOG) (see Appendix 6). KPS is a simple and widely used numerical instrument for rapidly quantifying the PS of an individual based on patients’ level of independence[38]. Studies have demonstrated a direct relationship between KPS and the perceived QOL in patients with cancer, including lung cancer[27,35]. Similarly, the ECOG is a five-grade observer rating of patients’ physical ability[35,37]. Both instruments (KPS and ECOG) have been found to be valid[37] including the Turkish language versions.[32,33]

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APPENDIX 5: Karnofsky performance scale

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APPENDIX 6: Eastern Cooperative Oncology Group (ECOG) performance status

The aims of the study were to determine how QOL is affected by chemotherapy, which other factors affect QOL apart from chemotherapy in this patient group and the relationship between QOL and performance status.


The study was a prospective-randomised research conducted in the oncology out-patient clinics of Dr. Lutfi Kirdar Kartal Training and Research Hospital, a 750-bed ministry of health facility located in Istanbul, Turkey.

Inclusion criteria required for patients were: diagnosis of metastatic [stage IV] lung cancer; inclusion within two weeks of diagnosis; not having yet received treatment. All participants were Turkish-speaking, conscious, and fully informed of their diagnosis. Additionally, mortality before completion of the third cycle of chemotherapy was accepted as an exclusion criterion.

A total of 17 out of 28 patients diagnosed with advanced SCLC, or stage IV NSCLC, and who were to receive platinum-based chemotherapy, fulfilled the criteria above, gave their consent and participated fully at every stage in this study. Four patients declined to give their consent; five patients who previously gave their consent decided not to participate before the first, second, third, or fourth chemotherapy treatment; and two patients died during the course of the study.

Setting, sample and analizing
1. After obtaining verbal consent, the patients’ demographic data was collected (age, gender, smoking history).

2. Structured interviews, each of which lasted between 30 to 90 minutes, were conducted based on the EORTC core questionnaire for quality of life in cancer patients QLQ–C30 (version 3.0), and the specific lung cancer module questionnaire EORTC QLQ-LC13. Interviews were conducted in outpatient clinics or by telephone, using validated Turkish translations of the above questionnaires on four separate occasions, pre-treatment and before the second, third and fourth cycle of chemotherapy.

3. Data related to the patients’ clincal and performance status (KPS and ECOG) were also recorded on four occasions during the study.

4. Statistical analysis was carried out using Prism® (version 5 for Mac OS X 2009). QOL differences between the baseline, first, second and third chemotherapy were analyzed using repeated- measures one-way analysis of variance (ANOVA). Pair-wise, post hoc comparison was performed between the groups at the baseline, first, second, and third chemotherapy applying the Tukey test. Correlation coefficients between global health status and age/smoking habit/ECOG/KPS were calculated using Pearson correlation analysis.


Table 1 provides demographic details of the patient group included in the study.

TABLE 1: Patients’ Demographics and Clinical Characteristics

Quality of life
As seen in both Figure 1 and Table 2, there was a continuous downward trend in General/ Global Health Status, from the baseline to the third chemotherapy. The decreases between the baseline and third chemotherapies (p< 0.005) and the second and third chemotherapies (p< 0.005) were statistically significant (F= 1.520).

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FIGURE 1: General health status scores at the four assessments *With respect to GHS, there was a continuous downward trend from the baseline to the third chemotherapy. The decreases between the baseline and third chemotherapies (p< 0.005) and the second and third chemotherapies (p< 0.005) were significant. (F= 1.520)

TABLE 2: QLQ scores according to QLQ-C30 at the four assessments

Other changes in QOL scores, according to assessment of the QLQ-C30 instrument, are summarized in Table 2. Regarding functional scales there were statistically important losses in all the functional areas: physical functioning decreased significantly between the baseline and third chemotherapies (p< 0.05, F= 3.336); role functioning between the baseline and third chemotherapies (p< 0,05, F= 1.016); emotional function between the baseline and third chemotherapies (p< 0.05, F= 3.173); cognitive functioning between the baseline and second chemotherapies, the baseline and third chemotherapies, and the first and third chemotherapies (p< 0.005, F= 4.152); and social functioning decreased significantly between the baseline and third chemotherapies and the first and third chemotherapies (p<0.05, F=6.14).

Concerning symptom scales there were significant increases in the reported incidence of the following clinical signs: nausea and vomiting increased significantly between the baseline and second chemotherapies and between the baseline and third chemotherapies (p< 0.05, F= 1.301); dyspnea symptoms increased from the first chemotherapy to the third (p< 0.023, F= 1.931); insomnia between the baseline and second chemotherapies and the baseline and third chemotherapies (p < 0.05, F= 1.523); and appetite loss increased significantly between the baseline and second chemotherapies, baseline and third chemotherapies, and between the first and third chemotherapies (p < 0.003, F= 1.668). Non - significant increases in fatigue, pain, constipation, diarrhoea and financial difficulties were observed.

Table 3 summarizes the trends in QOL with progressing treatment according to the lung cancer specific questionnaire (QLQLC13). Regarding treatment-related side effects, significant increases were recorded in all areas as follows: incidence of sore mouth increased significantly between the baseline and first, second, and third chemotherapies (p < 0.05, F= 1.085); dysphagia between the baseline and second and third chemotherapies (p < 0.05, F= 6.559); peripheral neuropathy between the baseline and first, second, and third chemotherapies (p < 0.05, F= 7.040); and alopecia increased significantly between baseline and first, second, and third chemotherapies, between first and second, and between first and third chemotherapies (p < 0.05, F= 0.9904).

TABLE 3: QLQ scores according to LC13 at the four assessments

On the other hand non-significant increases were observed for lung cancer associated symptoms (cough, haemoptysis, dyspnea), and site specific pain (chest, arm and shoulder, and other areas).

Other findings related to factors that may affect QOL
The mean age of the patients was 59.23±1.73 (Table 1). No significant correlation was found between age and general health status. (p> 0.05).

All of our patients had a smoking history (Table 1) with a mean packet year = 27.94±12.75, although none were smoking after diagnosis. No correlation between the number of packet years and QOL was found in this patient group.

Performance scales
As can be observed from Table 4, there was a significant difference in the ECOG performance between the baseline and second and third chemotherapies ( p< 0.05, F= 0. 923). In the same way, there were significant differences between the baseline and second and third chemotherapies, and between first and third chemotherapies for KFS values ( p< 0.05, F= 9.507).

TABLE 4: ECOG and KFS performance scale at the four assessments

Relationship between QOL and Performance status
As can be seen in Figure 2, there was a significant negative correlation between ECOG performance scale and QOL as reflected by General Health Status ( r = - 0.71, p< 0.05).

As shown in Figure 3, there was a significant positive correlation between KFS performance scale and GHS (r= 0.74, p< 0.05).

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FIGURE 2: Correlation between ECOG performance scale and Global Health Status

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FIGURE 3: Correlation between Karnofsky performance scalesand Global Health Status


Our research indicates that patients with advanced disease do not benefit from platinum-based chemotherapy in terms of QOL. Routine QOL assessment may encourage the development of treatment programs which minimize chemotherapy side-effects, while maximizing patients’ well being.

Our research did not show any significant relationship between age or smoking history and QOL. However, larger multi- center studies may help in providing a more comprehensive evaluation of the effect of various demographic and clinical variables on QOL in this setting.

Although performance status is not a true measure for QOL, it should be seen as an important prognostic factor and predictor of QOL, and should therefore be routinely assessed by physicians.[27]. Our study confirms the prognostic value of performance status in patients with advanced lung cancer.


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