Support Care Cancer DOI 10.1007/s00520-014-2255-7
REVIEW ARTICLE
Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review Floortje Mols & Tonneke Beijers & Gerard Vreugdenhil & Lonneke van de Poll-Franse
Received: 24 February 2014 / Accepted: 9 April 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Background The objective of this study was to systematically review all available literature concerning chemotherapyinduced peripheral neuropathy (CIPN) and quality of life (QOL) among cancer patients. Methods A computerized search of the literature was performed in December 2013. Articles were included if they investigated CIPN and QOL among cancer patients. Twentyfive articles were selected and were subjected to a 13-item quality checklist independently by two investigators. Results The methodological quality of the majority of the selected studies was adequate to high. The included studies differed tremendously with respect to study design (19 prospective studies, 5 cross-sectional, 1 both cross-sectional and prospective), patient population (lung, colorectal, ovarian, endometrial, cervical or breast cancer, lymphoma, acute lymphoblastic leukemia, or a mixed population), number of included patients (ranging from 14 to 1643), and ways to assess CIPN (objectively, subjectively, or both). Of the 25 included studies, 11 assessed the association of CIPN on patients’ QOL. While three of these studies did not find an association F. Mols (*) : L. van de Poll-Franse CoRPS - Center of Research on Psychology in Somatic Diseases, Department of Medical and Clinical Psychology, Tilburg University, PO Box 90153, 5000 LE Tilburg, The Netherlands e-mail:
[email protected] F. Mols : L. van de Poll-Franse Comprehensive Cancer Centre Netherlands (CCCN), Eindhoven Cancer Registry, Eindhoven, The Netherlands T. Beijers : G. Vreugdenhil Department of Internal Medicine, Maxima Medical Centre, Veldhoven, The Netherlands G. Vreugdenhil Department of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands
between CIPN and QOL, the others concluded that more CIPN was associated with a lower QOL. Implications for cancer survivors Although the included studies in this systematic review were very diverse, which impedes drawing firm conclusions on this topic, CIPN is likely to have a negative association with QOL. The variety of the studied patient populations and chemotherapeutic agents in the existing studies calls for further studies on this topic. These studies are preferably prospective in nature, include a large number of patients, and assess QOL and CIPN with validated questionnaires. Keywords Chemotherapy-induced peripheral neuropathy . Cancer . Quality of life
Introduction For an increasing number of patients, cancer has become a chronic disease. Raising incidence rates, earlier diagnosis, and improved treatments cause the number of cancer survivors to increase rapidly in the Western world. While quantity of life is the primary goal for most patients immediately after diagnosis, quality of life (QOL) becomes more important later on. However, due to the rising prevalence of cancer, more patients are living with the long-term side effects of cancer and its treatment which can have a negative impact on patients’ QOL. One of those possible side effects is chemotherapy-induced peripheral neuropathy (CIPN), which can occur due to treatment with certain chemotherapeutic agents like taxanes and platinum derivatives [1, 2]. Because of the growing prevalence of cancer, the broadening of the indications for chemotherapy [3–6], the development of new chemotherapeutic agents with CIPN side effects, and the lack of adequate treatment or preventive strategy against CIPN [7], it is likely that CIPN will become a major cancer survivorship issue.
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Recently, a systematic review on the influence of oxaliplatin administration on the long-term prevalence of oxaliplatininduced peripheral neuropathy showed that neuropathy was still present in a great amount of patients ≥12 months after the termination of therapy [8]. The general opinion is that CIPN has a negative influence on QOL [9], mainly because it may result in serious limitations in daily functioning [10, 11]. For instance, patients can experience symptoms like tingling, numbness, cramps, and aching or burning pain in their fingers or hands which can cause problems with regular daily activities like buttoning up a blouse, holding a pen, or opening a jar or bottle. Also, similar symptoms might be experienced in the toes or feet which can cause problems with standing, walking, climbing stairs, or driving. These symptoms can cause disruptions in physical functioning, daily activities, enjoyment, social relationships, and work [11]. Although CIPN can have a major influence on daily life and it has often been suggested that CIPN can have a negative influence on QOL, the literature on the association between CIPN and QOL is still scarce, and most studies describe CIPN and QOL separately and do not directly assess their association. Also, the studies on CIPN and QOL seem to differ tremendously with respect to the assessment of these constructs, the applied study design, the included patient population and chemotherapeutic agent, and the number of included patients. In order to shed some more light onto this area, a systematic review of the literature was performed. The goal of this review was to study all the available literature concerning CIPN and QOL among cancer patients. In this regard, we were especially interested in the association between CIPN and QOL.
reason: (1) if they included other patient populations besides cancer. After having applied our inclusion and exclusion criteria to the titles and abstracts of our initial hits, 37 articles seemed to meet our criteria. Hard copies were obtained of all studies and were reviewed by both investigators. After careful review, 25 articles actually fulfilled our selection criteria and were included in this review [12–36]. A flowchart of this selection procedure is shown in Fig. 1.
Quality assessment The methodological quality of each of the selected articles was assessed with a 13-item standardized checklist of predefined criteria by two investigators (FM and TB). The checklist was based on established criteria lists for systematic reviews [37, 38]. The criteria are presented in Table 1. Each item of a selected study, which matched our criteria, received 1 point. If an item did not meet our criteria or was described insufficiently or not at all, zero points were assigned. The highest possible score was thus 13. Studies scoring 75 % or more of the maximum attainable score (≥10 points) were arbitrarily considered to be of “high quality.” Studies scoring between 50 and 75 % (7–9 points) were rated as “adequate quality.” Studies scoring lower than 50 % (i.e., 18 years
EORTC QLQ-C30
QOL assessment
NCI CTAE, EORTC QLQ- EORTC QLQ-C30, EORTC QLQ-OV28 OV28 (contains a peripheral neuropathy subscale)
Radiation median= 64.2; chemotherapy median=62.9
–
Median=59, range=34– Trial-specific checklist 79
Mean age in years
Stage IIIB/IV non-small cell Mean=62.1, SD=10.3 lung cancer patients treated with carboplatin-paclitaxel Stage IVB recurrent or Age was shown in 5 persistent cervical cancer categories for 4 treated with 4 different treatments regimes of cisplatinpaclitaxel Cancer patients treated with No chemo: mean=61, taxanes, vinca-alkaloids SD=11.4; chemo: and/or platinum mean=62, SD=10.0 compounds and those who did not receive this treatment yet
Patients with various cancer types and stable CIPN
Ovarian cancer patients (stage IIb-IV) treated with paclitaxel- cisplatin or cyclophosphamide- cisplatin Patients with ovarian, fallopian tube, or extraovarian papillary serous cancer treated with paclitaxel-carboplatin or doxorubicin-carboplatin FIGO stage III or IV endometrial cancer, treatment with whole abdominal irradiation or doxorubicin-cisplatin Patients with stage IIb-IV epithelial ovarian cancer treated with paclitaxelcisplatin or cyclophosphamide-cisplatin Group A: 56 ovarian cancer patients receiving chemotherapy; group B: 43 ovarian cancer patients with neurotoxicity
Participants
Study qualityb
11
8
11
Yes
9
Not assessed 9
Yes
No
No
Not assessed 5
Not assessed 9
Not assessed 8
Not assessed 7
Influence CIPN on QOL
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USA
USA
Germany
Finland
Korea
Griffith et al. [21]
Hershman et al. [22]
Hilpert et al. [23]
Kautio et al. [24]
Kim et al. [25]
Size sample
Netherlands Cross935 men, 708 sectional women Japan Prospective 285 men, 92 women
Cross20 men, 10 sectional women
Cross24 boys, 13 sectional girls
USA
Ostchega et al. [29]
Ramchandren USA et al. [30]
Prospective 465 men, 257 women
Prospective 22 men, 10 women
Prospective 12 men, 32 women
Prospective 72 women
Cross50 women sectional Prospective 50 women
Prospective 15 men, 14 women
Design
Mols et al. [27] Morita et al. [28]
Lee et al. [26] UK
Country
Study
Table 2 (continued) CIPN assessmenta
Previously untreated patients Median=61, range=35– Assessed by physicians with stage IIIB/IV non75 using the WHO small cell lung cancer guidelines treated with cisplatin based treatment A self-designed 8-item Those free of cancer who had Men: mean=25, SD= subscale assessing 5.9; female: mean= received >720 mg of high symptoms of CIPN 49, SD=13.9 dose Cisplatin for testicular or ovarian cancer. Survivors of childhood acute Mean=14.4, range=8– Neuropathy impairment 18 scale, total neuropathy lymphoblastic leukemia score, Michigan treated with vincristine autonomic symptoms survey, bneurological exam
FACT/GOG-NTX, neuropathic pain scale, b quantitative sensory testing, deep tendon reflexes, grip strength Breast cancer patients (stage I- Median=51, range=34– FACT/GOG-NTX, NCI III) after paclitaxel therapy 80 CTCAE, btactile Breast cancer patients (stage I- Median=48, range=28– threshold, vibration 78 III) before paclitaxel threshold therapy – NCI CTCAE, and selfAdvanced ovarian cancer designed patient treated with paclitaxelquestionnaire, carboplatin b neurological assessment Breast, colorectal, Mean=54, range=35– Asked during consult, selflymphoma, uterine, lung 69 report in diary, b neurological exam and ovarian cancer patients with CIPN due to different chemotherapy regimes Patients with diffuse large B- Mean=55.9, range=21– Neuropathy symptoms 79 score, neuropathy cell lymphoma or follicular disability score, bnerve lymphoma conduction study Previously untreated Thalidomide: median= EORTC QLQ-LC14 patients with stage (contains a peripheral 63, range=35–84; IIIB/IV non-small cell neuropathy subscale) placebo: median=62, lung cancer treated with range=33–84 gemcitabine-carboplatin with or without thalidomide Colorectal cancer survivors Mean=69.4, SD=9.4 EORTC QLQ-CIPN20
Mean age in years
Chemotherapy-naïve subjects Mean=56.7, SD=10.4 with various cancer types
Participants
Not assessed 8
PedsQL 4.0
6
Yes
EORTC QOLQ Satisfaction with life scale
10
11 No
Yes
Not assessed 10
10
QOL-ACD
EORTC QLQ-C30
EORTC QLQ-C30, EORTC QLQ-LC14
Yes
Not assessed 8
EORTC QLQ-C30
SF-36
Not assessed 7
EORTC QLQ-C30
Not assessed 11
FACT-G
10
Study qualityb
Yes
Influence CIPN on QOL
FACT-G
QOL assessment
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Germany
Japan
USA
Sweden
USA
USA
Richter et al. [31]
Shimozuma et al. [32]
Smith et al. [33]
Sorbe et al. [34]
Tofthagen [35]
Wenzel et al. [36]
Size sample
Prospective 415 women
Cross8 men, 6 sectional women
Prospective 110 women
Prospective 82 men, 38 women
Prospective 300 women
Prospective 104 women
Design
Mean age in years
CIPN assessmenta
EORTC QLQ-OV28 Newly diagnosed patients with – (contains a peripheral advanced ovarian cancer neuropathy subscale) stage IA/G3-IV treated with carboplatin-paclitaxel Patient neurotoxicity Mean=50–54 per Node-positive breast cancer questionnaire, NCI treatment range=26– patients treated with taxaneCTCAE, FACT/GOG70 containing regimens. NTX, bstandardized neurological evaluation Cancer patients treated with Mean=59, SD=10.5 CIPN was determined paclitaxel, oxaliplatin, upon: symptom history, b loss of deep tendon single-agent docetaxel, reflexes, or the presence nanoparticle albuminof symmetrical stockingbound paclitaxel or glove numbness or cisplatin with CIPN. paresthesias beginning after chemotherapy treatment. NCI CTCAE Mean=63.3, range=28– Neurological Stage IIB-IV Epithelial 80 questionnaire, NCI ovarian cancer patients CTCAE, b2-point treated with docetaxeldiscrimination, carboplatin Romberg test, patellar reflex, Achilles reflex and vibratory sense Range=42–84 Self-designed interviews Purposive sample of lung, breast, colon cancer, multiple myeloma or cholangio-carcinoma 80 % between 41 and FACT/GOG-NTX Stage III epithelial ovarian 70 years cancer treated with paclitaxel-cisplatin
Participants
Study qualityb
Yes
Not assessed 4
Not assessed 10
EORTC QLQ-C30, EORTC QLQ OV28
Interviews
Fact-G, Fact-O
10
Not assessed 9
Not assessed 11
Not assessed 7
Influence CIPN on QOL
FACT/GOG-NTX (not in combination with the FACT-G)
FACT-G
EORTC QLQ-C30, EORTC QLQ-OV28
QOL assessment
b
a
A CIPN assessment was done by means of a neuropathy exam
Study quality was based upon the criteria listed in Table 1
CINQ chemotherapy-induced neurotoxicity questionnaire, CIPN chemotherapy-induced peripheral neuropathy, EORTC QLQ-C30 European Organisation of Research and Treatment of Cancer-Quality of Life Questionnaire Core, EORTC QLQ-CIPN20 EORTC QLQ-chemotherapy-induced peripheral neuropathy questionnaire, EORTC QLQ-OV28 EORTC QLQ-ovarian, EORTC QLQ-LC14 EORTC QLQlung cancer, EORTC QOLQ EORTC quality of life questionnaire, FACT-Cx Functional Assessment of Cancer Therapy-Cervix, FACT-G FACT–general, FACT/GOG-NTX FACT/Gynecologic Oncology Group-Neurotoxicity, FACT-O FACT-ovarian; FACT-TOI FACT-Trial Outcome Index, INCAT modified inflammatory neuropathy cause and treatment group sensory sum score, NCI CTCAE National Cancer Institute–Common terminology Criteria for adverse events, NCIC-CTG CTC National Institute of Canada-Clinical Trials Group Expanded Common Toxicity Criteria, PedsQL pediatric quality of life inventory, QOL-ACD quality of life questionnaire for cancer patients treated with anticancer drugs, SD standard deviation, SF-36 short form health survey, TNSc total neuropathy score clinical version, WHO World Health Organisation
Country
Study
Table 2 (continued)
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and autonomic subscale) was only used twice [17, 27]. The presence of CIPN was also often assessed by performing a neuropathy examination [16, 17, 21–26, 30, 32–34], although the content of this examination differed strongly by study. Finally, the National Cancer Institute – Common Terminology Criteria for adverse events (NCI CTCAE) was an often-used method to assess CIPN [17, 21–23, 32–34]. Studies that did find an association between CIPN and QOL Although all studies assessed both CIPN and QOL, only 11 studies actually assessed the association between CIPN and patients’ QOL. Eight of those studies did find an association between them [18, 20, 21, 25, 27, 29, 34]. Seven of these studies were of high quality according to our checklist, and four of them had a prospective design. One of those prospective high-quality studies assessed QOL and CIPN among 230 patients with advanced stage non-small cell lung cancer before treatment and 6, 12, and 26 weeks later [18]. Results showed that the FACT/GOG-NTX was positively correlated with the total FACT-G scores (r=0.30; p value=
