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Taxane Acute Pain Syndrome (TAPS) in Patients Receiving Taxane-Based Chemotherapy for Breast Cancer—A Systematic Review

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Taxane Acute Pain Syndrome (TAPS) in Patients Receiving Taxane-Based Chemotherapy for Breast Cancer—A Systematic Review Support Care Cancer DOI 10.1007/s00520-016-3256-5 REVIEW ARTICLE Taxane acute pain syndrome (TAPS) in patients receiving taxane-based chemotherapy for breast cancer—a systematic review Ricardo Fernandes1 & Sasha Mazzarello2 & Brian Hutton 3 & Risa Shorr4 & Habeeb Majeed5 & Mohammed FK Ibrahim1 & Carmel Jacobs1 & Michael Ong1 & Mark Clemons1,2 Received: 15 January 2016 /Accepted: 26 April 2016 # Springer-Verlag Berlin Heidelberg 2016 Abstract between study heterogeneity, a meta-analysis was not per- Background Taxane acute pain syndrome (TAPS) is charac- formed. The incidence of TAPS varied between taxanes: pac- terized by myalgias and arthralgias starting 24–48 h after litaxel (median 13.1 %, range 0.9–86 %), docetaxel (median taxane-based chemotherapy and lasting for 5–7days. 10.5 %, range 3.6–70 %), and nab-paclitaxel (26 %, range 14– Relatively little is known about its incidence and impact on 43 %). In the metastatic setting, median incidence was 30 % quality of life. (range 5.4–73 %), compared with 11.3 % (range 0.9–86 %) in Objectives A systematic review was conducted evaluating the the adjuvant setting. Three out of eight studies assessing qual- incidence of TAPS in breast cancer patients receiving taxane- ity of life demonstrated pain interference with daily activities. based chemotherapy. Conclusions The incidence of TAPS varies between taxanes, Methods Embase, Cochrane, and Ovid MEDLINE were regimens, and disease settings. In order to identify patients at searched from 1947 to July 2015. Data was sought from ran- the greatest risk of TAPS, and hence optimize its prevention domized controlled trials (RCTs), prospective and retrospec- and management, standardized methods of diagnosing and tive observational studies. Two reviewers independently measuring TAPS are needed. screened citations and full text articles. Outcomes of interest were the incidence of TAPS and its impact on quality of life. Keywords Breast cancer . Taxane chemotherapy . Pain . Results Of 980 citations identified, 51 relevant studies (27, Incidence . Quality of life 007 patients) were included. Data came from RCTs (12,357 patients), retrospective (6566 patients) and prospective obser- vational studies (6210 patients). Study sample sizes ranged from 14 to 4149 patients (median 152). Given the significance Background Taxanes such as docetaxel, paclitaxel, and nab-paclitaxel are – * Mark Clemons commonly used in the treatment of breast cancer [1 3]. A [email protected] commonly reported toxicity of taxanes is taxane acute pain syndrome (TAPS), also known as paclitaxel-associated acute 1 Department of Medicine, Division of Medical Oncology, The Ottawa pain syndrome or taxane-induced pain [4]. TAPS is typically Hospital Cancer Centre and University of Ottawa, 501 Smyth Road, characterized by myalgias and arthralgias appearing 24–48 h Ottawa, Canada after receiving taxane-based chemotherapy and lasting for 5– 2 Ottawa Hospital Research Institute and University of Ottawa, 7days[5]. TAPS can be debilitating for patients and lead to Ottawa, Canada dose delays, reductions, and discontinuation of potentially 3 Department of Epidemiology and Community Medicine, University curable therapy [4–7]. of Ottawa, Ottawa, Canada The incidence of TAPS varies between taxanes and is re- 4 The Ottawa Hospital, Ottawa, Canada portedly more common with docetaxel than with either pacli- 5 Department of Medicine, Division of Internal Medicine, The Ottawa taxel or nab-paclitaxel [4, 5, 8]. TAPS also appears to be more Hospital and University of Ottawa, Ottawa, Canada frequent in patients with breast cancer than in those with Support Care Cancer prostate, lung, or ovarian cancer [8–17]. The reasons for this Literature search variability in incidence are likely multi-factorial and reflect differences between taxanes, doses, combination regimens, An information specialist (RS) designed and executed an elec- patient populations, and variability in the co-administered tronic literature search to seek relevant citations from Embase, supportive care treatments that can themselves cause myalgias Cochrane, and Ovid MEDLINE from 1946 to July 7, 2015. (e.g., growth-colony stimulating factors) [2, 9, 10, 18]. The Key terms and their medical subject headings (MeSH) are use of different pain and toxicity assessment tools means that provided along with the full search strategy in Appendix 1. some studies report the incidence of chemotherapy-induced An independent PRESS review performed by a second librar- peripheral neuropathy (CIPN) as being the same as TAPS ian is provided in Appendix 1 [29]. [19, 20]. Clinically, TAPS is quite distinct from CIPN, with different mechanisms of action and temporal profiles. Study selection, data collection, and risk of bias However, the occurrence of TAPS can predispose to subse- assessment quent CIPN [21–24]. Thus, despite being relatively common in clinical Stage 1 screening was performed by three reviewers (SM, practice, the incidence of TAPS with different taxanes RF, and HM), who independently screened all citations and taxane-based regimens is not well established retrieved from the electronic search. Disagreements were [25–28]. Given the paucity of data addressing these discussed and resolved between reviewers. Stage 2 screen- knowledge gaps, the current systematic review was per- ing consisted of a full-text review of all potentially relevant formed. The objectives were to estimate the incidence citations by six reviewers working independently (SM, RF, of TAPS following a range of taxane-containing regi- HB, MC, CJ, and MI) to determine the final set of included mens in patients with breast cancer and to possibly articles. A PRISMA flow diagram was prepared to summa- identify potential predisposing factors for its occurrence. rize the process of study selection (Fig. 1), and a PRISMA Such risk factors could potentially be used to identify checklist was also completed during preparation of the re- patients a priori at greatest risk of experiencing TAPS port (Appendix 3)[30]. and to develop better prevention and treatment Once the final set of included studies was established, data strategies. were extracted by two reviewers independently using a pre- designed form implemented in Microsoft Excel version 2010 (Microsoft Corporation, Seattle, Washington, USA); any dis- crepancies were resolved by consensus discussion. The fol- Methods lowing information was collected from each study: authors, year and journal of publication, study design, number of pa- Research question and study eligibility criteria tients enrolled, patient eligibility criteria, relevant patient de- mographics, study duration, publication status, chemotherapy The systematic review was designed to summarize available duration and line, taxane type and frequency, stage of disease, information addressing the following research question: symptoms and incidence of TAPS, presence of concurrent BWhat are the incidence and risk factors of TAPS in steroid administration, rates of, and reasons for, chemotherapy breast cancer patients who have received taxane-based discontinuation, dose and type of analgesia, and quality of life chemotherapy?^ The Population-Intervention-Comparator- assessment. Authors were contacted to acquire other unpub- Outcome-Study Design (PICOS) framework was used to lished data. The Cochrane Collaboration’s tool for assessing structure the research question and its corresponding literature risk of bias in RCTs was used (Appendix 4)[31]. search. In the literature, breast cancer patients have the highest incidence of TAPS and hence were the population of interest. Data analysis Interventions of interest included any taxane-based chemo- therapy. Outcomes of interest included measures of the inci- If deemed appropriate, following exploration of study and dence of TAPS and quality of life. We also sought information patient characteristics to ensure sufficient clinical and meth- related to potential risk factors such as type of taxane, gender, odological homogeneity across studies, we planned to con- stage of disease, single agent versus combination chemother- duct meta-analyses using random effects models to combine apy, and concurrent medications. Randomized controlled tri- TAPS incidence data across studies. Following inspection of als (RCTs) as well as retrospective and prospective observa- the characteristics of included studies, the research team felt tional studies were eligible. Data on the incidence of TAPS there was a high degree of study heterogeneity in terms of was also included from randomized trials where one arm did study populations, study design, disease stage, and chemo- not receive a taxane. Animal studies were excluded, as were therapy regimen. These differences were viewed by the au- studies investigating CIPN. thors to preclude the data from meta-analysis. To synthesize Support Care Cancer Fig. 1 PRISMA flow diagram of Records identified and screened study selection process through database and abstract Records excluded due to searching after removal of irrelevancy duplicates (n=858) (N=980) Identification Identification Excluded (n=46): No reported TAPS data First screening (n=23) (n= 122) Cancer related pain (n=7) Quality of life (n=1) CIPN (n=4) Combination therapy (n=4) Case series and reports (n=6) Second screening Duplication (n=1) Screening (n= 76) Excluded (n=25): Quality of life (n=1) No TAPS data reported (n=13) Other tumour sites (n=9) Full-text articles or abstracts Duplication (n=1) assessed for eligibility Chemoradiation therapy (n=1)
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