Arthralgia and myalgia following taxane chemotherapy has been documented in the literature. However, these two toxicities associated with taxane treatment have not been closely examined in the literature, and data remain inconsistent in terms of the reported incidences of these toxicities. The purpose of this literature review was to provide a more comprehensive understanding of the incidence of taxane-induced arthralgia and myalgia, as well as to document the risk factors and preventative and therapeutic treatments that have been investigated.
Methods
A literature search was conducted in Ovid Medline, OldMedline, Embase, Embase Classic, and Cochrane Central Register of Controlled Trials using relevant subject headings and keywords such as: “arthralgia,” “myalgia,” “muscle pain,” “joint pain,” “taxane,” “chemotherapy,” “docetaxel,” “paclitaxel.”
Results
The reported incidences of arthralgia and myalgia were variable. Taxane chemotherapy was found to be associated with greater incidences of arthralgia and myalgia than non-taxane forms of chemotherapy. Moreover, docetaxel and nab-paclitaxel seem to be associated with lower incidences of arthralgia and myalgia than paclitaxel. Finally, the literature on prevention and therapeutic treatment of taxane-induced arthralgia and myalgia is scarce.
Conclusion
More studies should be done in order to more conclusively identify optimal therapeutic and preventative treatments as well as different risk factors. We recommend that a prospective study be done in order to better understand the true incidence of arthralgia and myalgia in patients being treated with the paclitaxel, docetaxel, and nab-paclitaxel.
MarkmanM. Managing taxane toxicities. Support Care Cancer2003; 11: 144–147.
2.
MarkmanMKennedyAWebsterK. Use of low-dose oral prednisone to prevent paclitaxel-induced arthralgia and myalgia. Gynecol Oncol1999; 72: 100–101.
3.
MarkmanM. Prevention of paclitaxel-associated arthralgia and myalgia. J Support Oncol2003; 1: 233–234.
4.
ChiKNChiaSKDixonR. A phase I pharmacokinetic study of the P-glycoprotein inhibitor, ONT-093, in combination with paclitaxel in patients with advanced cancer. Invest New Drugs2005; 23: 311–315.
5.
EarlHMVallierALHillerL. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2× 2 factorial randomized phase 3 trial. Lancet Oncol2014; 15: 201–212.
6.
EckhoffLNielsenMMoellerS. TAXTOX – a retrospective study regarding the side effects of docetaxel given as part of the adjuvant treatment to patients with primary breast cancer in Denmark from 2007 to 2009. Acta Oncol2011; 50: 1075–1082.
7.
KosmidisPAMylonakisNFountzilasG. Paclitaxel and carboplatin in inoperable non-small-cell lung cancer: a phase II study. Ann Oncol1997; 8: 697–699.
8.
ToyamaTYamashitaHHaraY. Biweekly paclitaxel in patients with metastatic breast cancer. Int J Clin Oncol2003; 8: 357–361.
9.
ShepherdFALatreilleJPaulK. Phase I dose-escalation trial of paclitaxel and ifosfamide in patients with advanced non-small cell lung cancer. Semin Oncol1996; 23: 84–90.
10.
AmadoriDFrassinetiGLZoliW. A phase I/II study of sequential doxorubicin and paclitaxel in the treatment of advanced breast cancer. Semin Oncol1996; 23: 16–22.
11.
BurtnessBWindsorSHolstonB. Adjuvant sequential dose-dense doxorubicin, paclitaxel, and cyclophosphamide (ATC) for high-risk breast cancer is feasible in the community setting. Cancer J1999; 5: 224–224.
12.
DavidsonNGChickJBPerrenTJ. A phase II study of single agent paclitaxel in patients at first relapse following initial chemotherapy for breast cancer. Clin Oncol1996; 8: 358–362.
13.
ItoYHorikoshiNWatanabeT. Phase II study of paclitaxel (BMS-181339) intravenously infused over 3 hours for advanced or metastatic breast cancer in Japan. Invest New Drugs1998; 16: 183–190.
14.
KerklaanBMDiérasVLe TourneauC. Phase I study of lonafarnib (SCH66336) in combination with trastuzumab plus paclitaxel in Her2/neu overexpressing breast cancer: EORTC study 16023. Cancer Chemoth Pharm2013; 71: 53–62.
15.
Mirzaei HR, Sabet Rasekh P, Nasrollahi F, et al. Dose-dense epirubicin and cyclophosphamide followed by docetaxel as adjuvant chemotherapy in node-positive breast cancer. Int J Breast Cancer 2013; 2013: 404396.
16.
MoulderSLHolmesFATolcherAW. A randomized phase 2 trial comparing 3-hour versus 96-hour infusion schedules of paclitaxel for the treatment of metastatic breast cancer. Cancer2010; 116: 814–821.
17.
RiccardiAPugliesePDanovaM. A phase II study of sequential 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel in advanced breast cancer (Protocol PV BC 97/01). Br J Cancer2001; 85: 141–141.
18.
SaibilSFitzgeraldBFreedmanOC. Incidence of taxane-induced pain and distress in patients receiving chemotherapy for early-stage breast cancer: a retrospective, outcomes-based survey. Curr Oncol2010; 17: 42–42.
19.
SeidmanADTierstenAHudisC. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol1995; 13: 2575–2581.
20.
SmithREAndersonSJLemberskyBC. Phase II trial of a doxorubicin/docetaxel doublet for locally advanced and metastatic breast cancer: results from national surgical adjuvant breast and bowel project trial BP-57. Clin Breast Cancer2014; 5: 208–215.
21.
TakabatakeDTairaNHaraF. Feasibility study of docetaxel with cyclophosphamide as adjuvant chemotherapy for Japanese breast cancer patients. Jpn J Clin Oncol2009; 39: 478–483.
22.
ThorntonLMCarsonWEShapiroCL. Delayed emotional recovery after taxane-based chemotherapy. Cancer2008; 113: 638–647.
23.
Abu-KhalafMMWindsorSEbisuK. Five-year update of an expanded phase II study of dose-dense and-intense doxorubicin, paclitaxel and cyclophosphamide (ATC) in high-risk breast cancer. Oncology2005; 69: 372–383.
24.
LluchAOjebaBColomerR. Doxorubicin and paclitaxel in advanced breast carcinoma: importance of prior adjuvant anthracycline therapy. Cancer2000; 89: 2169–2175.
25.
MamounasEPBryantJLemberskyB. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol2005; 23: 3686–3696.
26.
JonesSESavinMAHolmesFA. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol2006; 24: 5381–5387.
27.
BishopJFDewarJTonerGC. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol1999; 17: 2355–2364.
28.
BoyerMJZalcbergJOlverIN. Phase I study of paclitaxel and oral etoposide in previously untreated non-small-cell and extensive small-cell lung cancer. Ann Oncol1997; 8: 485–489.
29.
CantuMGBudaAParmaG. Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J Clin Oncol2002; 20: 1232–1237.
30.
GatzemeierUvon PawelJGottfriedM. Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non–small-cell lung cancer. J Clin Oncol2000; 18: 3390–3399.
31.
GiacconeGSplinterTADebruyneC. Randomized study of paclitaxel-cisplatin versus cisplatin-teniposide in patients with advanced non-small-cell lung cancer. The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol1998; 16: 2133–2141.
32.
GrecoFASpigelDRKuzurME. Paclitaxel/carboplatin/gemcitabine versus gemcitabine/vinorelbine in advanced non–small-cell lung cancer: a phase II/III study of the Minnie Pearl Cancer Research Network. Clin Lung Cancer2007; 8: 483–487.
33.
KrzakowskiMRamlauRJassemJ. Phase III trial comparing vinflunine with docetaxel in second-line advanced non–small-cell lung cancer previously treated with platinum-containing chemotherapy. J Clin Oncol2010; 28: 2167–2173.
34.
KubotaKKawaharaMOgawaraM. Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III study. Lancet Oncol2008; 9: 1135–1142.
35.
LinYCChangHKChenJS. A phase II randomized study of two taxanes and cisplatin for metastatic breast cancer after anthracycline: a final analysis. Jpn J Clin Oncol2007; 37: 23–29.
36.
LoeschDGrecoFASenzeNN. Phase III multicenter trial of doxorubicin plus cyclophosphamide followed by paclitaxel compared with doxorubicin plus paclitaxel followed by weekly paclitaxel as adjuvant therapy for women with high-risk breast cancer. J Clin Oncol2010; 28: 2958–2965.
37.
O’BrienMERSplinterTSmitEF. Carboplatin and paclitaxol (Taxol) as an induction regimen for patients with biopsy-proven stage IIIA N2 non-small cell lung cancer: an EORTC phase II study (EORTC 08958). Eur J Cancer2003; 39: 1416–1422.
38.
SeidmanADTierstenAHudisC. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol1995; 13: 2575–2581.
39.
SmithREAndersonSJBrownA. Phase II trial of doxorubicin/docetaxel/cyclophosphamide for locally advanced and metastatic breast cancer: results from NSABP trial BP-58. Clin Breast Cancer2002; 3: 333–340.
40.
KosmidisPAKalofonosHPChristodoulouC. Paclitaxel and gemcitabine versus carboplatin and gemcitabine in patients with advanced non-small-cell lung cancer. A phase III study of the Hellenic Cooperative Oncology Group. Ann Oncol2008; 19: 115–122.
41.
SocinskiMABondarenkoIKarasevaNA. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non–small-cell lung cancer: final results of a phase III trial. J Clin Oncol2012; 30: 2055–2062.
42.
JacobsonSDLoprinziCLSloanJA. Glutamine does not prevent paclitaxel-associated myalgia and arthralgia. J Support Oncol2003; 1: 274–278.
43.
NguyenVHLawrenceHJ. Use of gabapentin in the prevention of taxane-induced arthralgia and myalgia. J Clin Oncol2004; 22: 1767–1769.
44.
SavareseDBoucherJCoreyB. Glutamine treatment of paclitaxel-induced myalgia and arthralgia. J Clin Oncol1998; 16: 3918–3919.
45.
YamamotoKHoshiaiHNodaK. Effects of Shakuyaku-kanzo-to on muscle pain from combination chemotherapy with paclitaxel and carboplatin. Gynecol Oncol2001; 81: 333–334.
46.
YoshidaTSawaTIshiguroT. The efficacy of prophylactic Shakuyaku-kanzo-to for myalgia and arthralgia following carboplatin and paclitaxel combination chemotherapy for non-small cell lung cancer. Support Care Cancer2009; 17: 315–320.
47.
CrewKDGreenleeHCapodiceJ. Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol2007; 25: 3877–3883.
48.
VaseyPA. Survival and longer term toxicity results of the SCOTROC study: docetaxel-carboplatin (DC) vs. paclitaxel-carboplatin (PC) in epithelial ovarian cancer (EOC) (abstract). Proc Am Soc Clin Oncol2002; 21: 202a–202a.
49.
LoprinziCLReevesBNDakhilSR. Natural history of paclitaxel-associated acute pain syndrome: prospective cohort study NCCTG N08C1. J Clin Oncol2011; 29: 1472–1478.
50.
LoprinziCLMaddocks-ChristiansonKWolfSL. The paclitaxel acute pain syndrome: sensitization of nociceptors as the putative mechanism. Cancer J2007; 13: 399–403.
51.
ReevesBNDakhilSRSloanJA. Further data supporting that paclitaxel-associated acute pain syndrome is associated with development of peripheral neuropathy. Cancer2012; 118: 5171–5178.
52.
GarrisonJAMcCuneJSLivingstonRB. Myalgias and arthralgias associated with paclitaxel. Oncology2003; 17: 271–288.
