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

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Treatment of Taxane Acute Pain Syndrome (TAPS) in Cancer Patients Receiving Taxane-Based Chemotherapy—A Systematic Review Support Care Cancer (2016) 24:1583–1594 DOI 10.1007/s00520-015-2941-0 ORIGINAL ARTICLE Treatment of taxane acute pain syndrome (TAPS) in cancer patients receiving taxane-based chemotherapy—a systematic review Ricardo Fernandes1 & Sasha Mazzarello2 & Habeeb Majeed3 & Stephanie Smith 2 & Risa Shorr4 & Brian Hutton5 & Mohammed FK Ibrahim1 & Carmel Jacobs1 & Michael Ong1 & Mark Clemons1,2,6 Received: 21 May 2015 /Accepted: 3 September 2015 /Published online: 19 September 2015 # Springer-Verlag Berlin Heidelberg 2015 Abstract randomized open-label trials 76 patients), and one was a ret- Background Taxane acute pain syndrome (TAPS) is charac- rospective study (10 patients). The agents investigated includ- terized by myalgias and arthralgias starting 1–3 days and last- ed gabapentin, amifostine, glutathione, and glutamine. Study ing 5–7 days after taxane-based chemotherapy. Despite nega- sizes ranged from 10 to 185 patients. Given the heterogeneity tively impacting patient’s quality of life, little is known about of study designs, a narrative synthesis of results was per- the optimal TAPS management. A systematic review of treat- formed. Neither glutathione (QoL, p = 0.30, no 95 % CI re- ment strategies for TAPS across all tumor sites was performed. ported) nor glutamine (mean improvement in average pain Methods Embase, Ovid MEDLINE(R), and the Cochrane was 0.8 in both treatment arms, p = 0.84, no 95 % CI reported) Central Register of Controlled Trials were searched from were superior to placebo. Response to amifostine (pain re- 1946 to October 2014 for trials reporting the effectiveness of sponse) and gabapentin (reduction in taxane-induced arthral- different treatments of TAPS in cancer patients receiving gias and myalgias) was 36 % (95 % CI, 16–61 %) and 90 % taxane-based chemotherapy. Two individuals independently (no 95 % CI data reported), respectively. screened citations and full-text articles for eligibility. Conclusions Despite its prevalence in patients receiving Outcome measures included type of treatment and response taxane-based chemotherapies, TAPS remains poorly of myalgias, arthralgias, pain, and quality of life (QoL). researched and few studies evaluate its optimal management. Results Of 1614 unique citations initially identified, five stud- If the management of patients is to be improved, more pro- ies met the pre-specified eligibility criteria. Two were random- spective trials are needed. ized placebo-controlled trials (225 patients), two were Keywords Taxane acute pain syndrome . Docetaxel . Paclitaxel . Gabapentin . Amifostine . Glutathione . * Mark Clemons Glutamine [email protected] 1 Division of Medical Oncology, Department of Medicine, The Ottawa Background Hospital and University of Ottawa, Ottawa, Ontario, Canada 2 Ottawa Hospital Research Institute and University of Ottawa, Taxane-based chemotherapeutic agents, such as docetaxel, Ottawa, Ontario, Canada paclitaxel, nab-paclitaxel, and cabazitaxel, are commonly 3 Division of Internal Medicine, Department of Medicine, The Ottawa used in the treatment of many malignancies [1]. Taxanes have Hospital, Ottawa, Ontario, Canada been associated with taxane acute pain syndrome (TAPS), also 4 The Ottawa Hospital, Ottawa, Ontario, Canada known as paclitaxel-associated acute pain (P-APS) and 5 Department of Epidemiology and Community Medicine, University taxane-induced pain. TAPS is characterized by myalgia and of Ottawa, Ottawa, Ontario, Canada arthralgia, starting 1–3 days after taxane-based treatment, and 6 Division of Medical Oncology, The Ottawa Hospital Cancer Centre, usually lasting for 5–7 days [2]. While TAPS shares some 501 Smyth Road, Ottawa, Canada clinical characteristics with chemotherapy-induced peripheral 1584 Support Care Cancer (2016) 24:1583–1594 neuropathy (CIPN) (and indeed TAPS can be associated with combination) in the neoadjuvant, adjuvant, or metastatic set- subsequent CIPN) [3–13], TAPS is usually completely re- tings. Outcome measures of interest included the type of treat- solved prior to the next cycle of chemotherapy [2]. While ment for TAPS, as well as the response of myalgias, arthral- the incidence of TAPS varies according to tumor type and gias, pain, and quality of life using validated scales. taxane regimen (Table 1), its pathophysiology remains poorly Randomized, retrospective, or prospective studies published understood [2, 12, 13]. in English were included. Studies were excluded if they en- TAPS is clinically significant as it not only affects physical rolled patients with prior neurologic comorbidities. function and quality of life but can also lead to chemotherapy dose delays, reductions, and discontinuation [11]. A number Literature search of approaches for its prevention and treatment have been sug- gested, including non-steroidal anti-inflammatory drugs An information specialist (RS) designed and executed an elec- (NSAIDs) [17], corticosteroids [18], antihistamines [19], tronic literature search to identify relevant citations from gabapentin [20–21], pregabalin [22], and shakuyaku-kanzo- Embase Classic and Embase from 1947 to October 2014, to [23–24]. However, most of these agents have been evalu- Ovid MEDLINE(R) In-Process & other non-indexed cita- ated in the context of treatment for CIPN and not for TAPS. In tions, and Ovid MEDLINE(R) from 1946 to September order to establish the strength of evidence underlying different 2014. Search terms and their medical subject heading treatment options for TAPS, a systematic review was per- (MeSH) equivalents are shown in Appendix 1 where the formed. Although breast and prostate cancer have been most MEDLINE search strategy is provided. commonly reported in the literature to be associated with TAPS, a systematic review was performed including all tumor Study screening and selection sites for which taxane-based chemotherapy are used. Stage 1 screening consisted of titles and abstracts identified from the literature search by two independent reviewers (SM, Methods RF, HM). Disagreements were discussed and resolved be- tween reviewers. Stage 2 screening consisted of a full-text Study objective and eligibility criteria review of all potentially relevant citations identified during Stage 1 screening by two independent reviewers (SM, RF, This systematic review was performed to identify and evaluate SS, MC, CJ, and MI). Results from the screening process strategies in the literature for the management of TAPS in are presented in a PRISMA flow diagram (Fig. 1). cancer patients receiving taxane-based chemotherapy. The population-intervention-comparator-outcome study design Data collection (PICOS) framework was used to structure the research ques- tion for the review and its corresponding literature search. The A pre-designed data collection form implemented in population of interest included patients diagnosed with cancer. Microsoft Excel was utilized for data extraction. All data No restrictions were placed on primary tumor sites. was extracted independently by two reviewers and subse- Interventions of interest incorporated any taxane-based che- quently compared for discrepancies which were resolved by motherapy regimen (either as a single agent or in discussion. We collected information related to publication Table 1 Reported incidence of taxane acute pain syndrome from Taxane Chemotherapy regimen Study population Incidence of TAPS (%) past literature Paclitaxel [8] AC-T Adjuvant breast cancer 12 Docetaxel [3–6] TC Adjuvant breast cancer 10–22 FEC-D 33 TAC 10–28 Docetaxel [7] Single agent Metastatic breast cancer 26 Nab-paclitaxel [9] Single agent Metastatic breast cancer 7–26 Docetaxel [10] Single agent Metastatic prostate cancer 1–10 Docetaxel [14] Single agent Metastatic lung cancer 1.5–16.1 Docetaxel [15] Carboplatin plus docetaxel Metastatic ovarian cancer 31 Paclitaxel [16] CT or PT Adjuvant ovarian cancer 9.6–36.7 TC docetaxel/cyclophosphamide; FEC-D docetaxel after prior 5-fluorouracil-epirubicin-cyclophosphamide; AC- T docetaxel after prior doxorubicin-cyclophosphamide; CT carboplatin/paclitaxel; PT cisplatin/paclitaxel Support Care Cancer (2016) 24:1583–1594 1585 Fig. 1 Systematic review Records identified and screened supplement: PRISMA flow through database and abstract diagram review supplement: searching after removal of PRISMA flow diagram. CIPN Identification duplicates chemotherapy-induced peripheral (n=1608) neuropathy Records excluded due to irrelevancy (n= 1571) Record screened in full text Screening (n=39) Full-text arcles or abstracts Excluded (n=33): Eligibility assessed for eligibility CIPN (n= 5) No TAPS treatment mention (n=5) (n=26) Late arthropathy treatment (n= 1) Cancer related pain (n=1) Duplicate publication (n= 1) Studies included in qualitative synthesis Included (n=5) CIPN - chemotherapy induced peripheral neuropathy characteristics (year, journal, and authors), patient characteris- authors that there were significant clinical differences that pre- tics (performance status, median age, disease stage, and sites cluded the data from meta-analysis. In the light of these dif- of disease), intervention characteristics (chemotherapy line, ferences, a narrative strategy to summary of study-specific taxane type and frequency, and TAPS treatment), and out- results was performed. comes of interest (response of pain, myalgias, and arthralgias). Studies were also independently assessed for risk of bias by two reviewers using the Cochrane Collaboration’sriskofbias tool for randomized trials [25] which assesses for sources of Findings selection, performance, detection,
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