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01-04-2013 | Original Article

Phase II study of glucosamine with chondroitin on aromatase inhibitor-associated joint symptoms in women with breast cancer

Authors: Heather Greenlee, Katherine D. Crew, Theresa Shao, Grace Kranwinkel, Kevin Kalinsky, Matthew Maurer, Lois Brafman, Beverly Insel, Wei Yann Tsai, Dawn L Hershman

Published in: Supportive Care in Cancer | Issue 4/2013

Abstract

Purpose

Many women with hormone receptor-positive breast cancer discontinue effective aromatase inhibitor (AI) treatment due to joint symptoms.

Methods

We conducted a single-arm, open-label, phase II study evaluating glucosamine-sulfate (1,500 mg/day) + chondroitin-sulfate (1,200 mg/day) for 24 weeks to treat joint pain/stiffness in postmenopausal women with early stage breast cancer who developed moderate-to-severe joint pain after initiating AIs. The primary endpoint was improvement in pain/stiffness at week 24 assessed by the Outcome Measure in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria. Secondary endpoints assessed changes in pain, stiffness, and function using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index for hips/knees and the Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) for hands/wrists. The Brief Pain Inventory (BPI) assessed pain interference, severity, and worst pain.

Results

Of 53 patients enrolled, 39 were evaluable at week 24. From baseline to week 24, 46 % of patients improved according to OMERACT-OARSI criteria. At week 24, there were improvements (all P < 0.05) in pain and function as assessed by WOMAC and M-SACRAH, and in pain interference, severity, and worst pain as assessed by BPI. Estradiol levels did not change from baseline. The most commonly reported side effects were headache (28 %), dyspepsia (15 %), and nausea (17 %).

Conclusions

In this single-arm study, 24 weeks of glucosamine/chondroitin resulted in moderate improvements in AI-induced arthralgias, with minimal side effects, and no changes in estradiol levels. These results suggest a need to evaluate efficacy in a placebo-controlled trial.

Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, Sahmoud T, Group AT (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359(9324):2131–2139PubMedCrossRef

Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL (2003) A randomized trial of letrozole in postmenopausal women after 5 years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 349(19):1793–1802PubMedCrossRef

Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365(9453):60–62PubMedCrossRef

Thurlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardly A, Price KN, Goldhirsch A (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353(26):2747–2757PubMedCrossRef

Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL (2005) Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 97(17):1262–1271PubMedCrossRef

Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lonning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM (2004) A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350(11):1081–1092PubMedCrossRef

Crew KD, Greenlee H, Capodice J, Raptis G, Brafman L, Fuentes D, Sierra A, Hershman DL (2007) Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol 25(25):3877–3883. doi:10.1200/JCO.2007.10.7573 PubMedCrossRef

Sestak I, Cuzick J, Sapunar F, Eastell R, Forbes JF, Bianco AR, Buzdar AU (2008) Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis. Lancet Oncol 9(9):866–872. doi:10.1016/S1470-2045(08)70182-7 PubMedCrossRef

Henry NL, Giles JT, Ang D, Mohan M, Dadabhoy D, Robarge J, Hayden J, Lemler S, Shahverdi K, Powers P, Li L, Flockhart D, Stearns V, Hayes DF, Storniolo AM, Clauw DJ (2008) Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors. Breast Cancer Res Treat 111(2):365–372. doi:10.1007/s10549-007-9774-6 PubMedCrossRef

10.

Mao JJ, Stricker C, Bruner D, Xie S, Bowman MA, Farrar JT, Greene BT, DeMichele A (2009) Patterns and risk factors associated with aromatase inhibitor-related arthralgia among breast cancer survivors. Cancer 115(16):3631–3639. doi:10.1002/cncr.24419 PubMedCrossRef

11.

Mortimer JE (2010) Managing the toxicities of the aromatase inhibitors. Curr Opin Obstet Gynecol 22(1):56–60. doi:10.1097/GCO.0b013e328334e44e PubMedCrossRef

12.

Hershman DL, Kushi LH, Shao T, Buono D, Kershenbaum A, Tsai WY, Fehrenbacher L, Lin Gomez S, Miles S, Neugut AI (2010) Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol 28(27):4120–4128. doi:10.1200/JCO.2009.25.9655 PubMedCrossRef

13.

Hershman DL, Shao T, Kushi LH, Buono D, Tsai WY, Fehrenbacher L, Kwan M, Gomez SL, Neugut AI (2011) Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat 126(2):529–537. doi:10.1007/s10549-010-1132-4 PubMedCrossRef

14.

Rao JK, Mihaliak K, Kroenke K, Bradley J, Tierney WM, Weinberger M (1999) Use of complementary therapies for arthritis among patients of rheumatologists. Ann Intern Med 131(6):409–416PubMed

15.

Barnes PM, Bloom B, Nahin RL (2008) Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report 12:1–23PubMed

16.

Chou R, McDonagh MS, Nakamoto E, Griffin J (2011) Analgesics for osteoarthritis: an update of the 2006 comparative effectiveness review [Internet]. AHRQ comparative effectiveness reviews, vol 38. Agency for Healthcare Research and Quality (US), Rockville (MD)

17.

Kapoor M, Mineau F, Fahmi H, Pelletier JP, Martel-Pelletier J (2011) Glucosamine sulfate reduces prostaglandin E2 production in osteoarthritic chondrocytes through inhibition of microsomal PGE synthase-1. J Rheumatol. doi:10.3899/jrheum.110621

18.

Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M (2011) Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients. Arch Phys Med Rehabil 92(8):1185–1193. doi:10.1016/j.apmr.2011.03.009 PubMedCrossRef

19.

Wildi LM, Raynauld JP, Martel-Pelletier J, Beaulieu A, Bessette L, Morin F, Abram F, Dorais M, Pelletier JP (2011) Chondroitin sulphate reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients starting as early as 6 months after initiation of therapy: a randomised, double-blind, placebo-controlled pilot study using MRI. Ann Rheum Dis 70(6):982–989. doi:10.1136/ard.2010.140848 PubMedCrossRef

20.

Setnikar I, Cereda R, Pacini MA, Revel L (1991) Antireactive properties of glucosamine sulfate. Arzneimittelforschung 41(2):157–161PubMed

21.

Shikhman AR, Kuhn K, Alaaeddine N, Lotz M (2001) N-acetylglucosamine prevents IL-1 beta-mediated activation of human chondrocytes. J Immunol 166(8):5155–5160PubMed

22.

Bassleer C, Rovati L, Franchimont P (1998) Stimulation of proteoglycan production by glucosamine sulfate in chondrocytes isolated from human osteoarthritic articular cartilage in vitro. Osteoarthritis Cartilage 6(6):427–434. doi:10.1053/joca.1998.0146 PubMedCrossRef

23.

Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC (2002) Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 162(18):2113–2123PubMedCrossRef

24.

Lippiello L, Woodward J, Karpman R, Hammad TA (2000) In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate. Clin Orthop Relat Res 381:229–240PubMedCrossRef

25.

Clegg DO, Reda DJ, Harris CL, Klein MA, O’Dell JR, Hooper MM, Bradley JD, Bingham CO 3rd, Weisman MH, Jackson CG, Lane NE, Cush JJ, Moreland LW, Schumacher HR Jr, Oddis CV, Wolfe F, Molitor JA, Yocum DE, Schnitzer TJ, Furst DE, Sawitzke AD, Shi H, Brandt KD, Moskowitz RW, Williams HJ (2006) Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 354(8):795–808PubMedCrossRef

26.

Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15(12):1833–1840PubMed

27.

Sautner J, Andel I, Rintelen B, Leeb BF (2004) Development of the M-SACRAH, a modified, shortened version of SACRAH (Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands). Rheumatology (Oxford) 43(11):1409–1413CrossRef

28.

Cleeland CS, Ryan KM (1994) Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore 23(2):129–138PubMed

29.

Brady MJ, Cella DF, Mo F, Bonomi AE, Tulsky DS, Lloyd SR, Deasy S, Cobleigh M, Shiomoto G (1997) Reliability and validity of the functional assessment of cancer therapy-breast quality-of-life instrument. J Clin Oncol 15(3):974–986PubMed

30.

Fallowfield LJ, Leaity SK, Howell A, Benson S, Cella D (1999) Assessment of quality of life in women undergoing hormonal therapy for breast cancer: validation of an endocrine symptom subscale for the FACT-B. Breast Cancer Res Treat 55(2):189–199PubMedCrossRef

31.

Anderson JW, Nicolosi RJ, Borzelleca JF (2005) Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy. Food Chem Toxicol 43(2):187–201PubMedCrossRef

32.

Pham T, van der Heijde D, Altman RD, Anderson JJ, Bellamy N, Hochberg M, Simon L, Strand V, Woodworth T, Dougados M (2004) OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage 12(5):389–399. doi:10.1016/j.joca.2004.02.001 PubMedCrossRef

33.

Rastelli AL, Taylor ME, Gao F, Armamento-Villareal R, Jamalabadi-Majidi S, Napoli N, Ellis MJ (2011) Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Res Treat 129(1):107–116. doi:10.1007/s10549-011-1644-6 PubMedCrossRef

34.

Khan QJ, Reddy PS, Kimler BF, Sharma P, Baxa SE, O’Dea AP, Klemp JR, Fabian CJ (2010) Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer. Breast Cancer Res Treat 119(1):111–118. doi:10.1007/s10549-009-0495-x PubMedCrossRef

35.

Prieto-Alhambra D, Javaid MK, Servitja S, Arden NK, Martinez-Garcia M, Diez-Perez A, Albanell J, Tusquets I, Nogues X (2011) Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study. Breast Cancer Res Treat 125(3):869–878. doi:10.1007/s10549-010-1075-9 PubMedCrossRef

36.

Henry NL, Banerjee M, Wicha M, Van Poznak C, Smerage JB, Schott AF, Griggs JJ, Hayes DF (2011) Pilot study of duloxetine for treatment of aromatase inhibitor-associated musculoskeletal symptoms. Cancer 117(24):5469–5475. doi:10.1002/cncr.26230 PubMedCrossRef

37.

Crew KD, Capodice JL, Greenlee H, Brafman L, Fuentes D, Awad D, Yann Tsai W, Hershman DL (2010) Randomized, blinded, sham-controlled trial of acupuncture for the management of aromatase inhibitor-associated joint symptoms in women with early-stage breast cancer. J Clin Oncol 28(7):1154–1160. doi:10.1200/JCO.2009.23.4708 PubMedCrossRef

38.

Crew KD, Capodice JL, Greenlee H, Apollo A, Jacobson JS, Raptis G, Blozie K, Sierra A, Hershman DL (2007) Pilot study of acupuncture for the treatment of joint symptoms related to adjuvant aromatase inhibitor therapy in postmenopausal breast cancer patients. J Cancer Surviv 1(4):283–291. doi:10.1007/s11764-007-0034-x PubMedCrossRef

39.

Mao JJ, Bruner DW, Stricker C, Farrar JT, Xie SX, Bowman MA, Pucci D, Han X, DeMichele A (2009) Feasibility trial of electroacupuncture for aromatase inhibitor-related arthralgia in breast cancer survivors. Integr Cancer Ther 8(2):123–129. doi:10.1177/1534735409332903 PubMedCrossRef

40.

Galantino ML, Desai K, Greene L, Demichele A, Stricker CT, Mao JJ (2011) Impact of yoga on functional outcomes in breast cancer survivors with aromatase inhibitor-associated arthralgias. Integr Cancer Ther. doi:10.1177/1534735411413270

41.

Briot K, Tubiana-Hulin M, Bastit L, Kloos I, Roux C (2010) Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer: the ATOLL (Articular Tolerance of Letrozole) study. Breast Cancer Res Treat 120(1):127–134. doi:10.1007/s10549-009-0692-7 PubMedCrossRef

42.

Gabay C, Medinger-Sadowski C, Gascon D, Kolo F, Finckh A (2011) Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial at a single center. Arthritis Rheum 63(11):3383–3391. doi:10.1002/art.30574 PubMedCrossRef

43.

Wilkens P, Scheel IB, Grundnes O, Hellum C, Storheim K (2010) Effect of glucosamine on pain-related disability in patients with chronic low back pain and degenerative lumbar osteoarthritis: a randomized controlled trial. JAMA 304(1):45–52. doi:10.1001/jama.2010.893 PubMedCrossRef

44.

Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, Haythornthwaite JA, Jensen MP, Kerns RD, Ader DN, Brandenburg N, Burke LB, Cella D, Chandler J, Cowan P, Dimitrova R, Dionne R, Hertz S, Jadad AR, Katz NP, Kehlet H, Kramer LD, Manning DC, McCormick C, McDermott MP, McQuay HJ, Patel S, Porter L, Quessy S, Rappaport BA, Rauschkolb C, Revicki DA, Rothman M, Schmader KE, Stacey BR, Stauffer JW, von Stein T, White RE, Witter J, Zavisic S (2008) Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain 9(2):105–121. doi:10.1016/j.jpain.2007.09.005 PubMedCrossRef

Title: Phase II study of glucosamine with chondroitin on aromatase inhibitor-associated joint symptoms in women with breast cancer
Authors: Heather Greenlee
Katherine D. Crew
Theresa Shao
Grace Kranwinkel
Kevin Kalinsky
Matthew Maurer
Lois Brafman
Beverly Insel
Wei Yann Tsai
Dawn L Hershman
Publication date: 01-04-2013
Publisher: Springer-Verlag
Published in: Supportive Care in Cancer / Issue 4/2013
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-012-1628-z

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