How are Interactions Taken into Account in Studies on Conventional and Complementary Therapies for Breast Cancer Patients with Menopausal Complaints?

Abstract

Introduction: Postmenopausal symptoms in breast cancer patients undergoing antihormone treatment lead to high drop-out rates from the therapy. From the therapeutic point of view, methods of both conventional and complementary medicine are concerned. Interactions are being discussed in cases of natural substances. However, they are also relevant for conventional medical substances. The aim of this analysis is to answer the question as to what extent potential interactions are taken into account in clinical studies and reviews on supportive therapies. Materials and Methods: Clinical studies and reviews were identified by means of a systematic search and analysed with regard to the consideration of potential interactions. Results: Altogether 46 clinical studies and one Cochrane review were found. Among the 35 studies on conventional drug therapies, 5 (14 %) took possible interactions into account. Among the 17 studies on complementary medicine, there were 2 (11.7 %) such publications. The Cochrane review did not mention interactions. Discussion: For future studies in which interactions cannot be excluded, a strategy to control for their clinically relevant consequences should be developed. The present authors suggest that the use of survival and recurrence data as secondary endpoints, also for studies on purely supportive therapies, is a reasonable approach. The resulting considerations for study routines are listed thematically.

Zusammenfassung

Einleitung: Postmenopausale Symptome bei Mammakarzinompatientinnen unter antihormoneller Therapie führen zu einer hohen Abbrecherrate der Therapie. Therapeutisch kommen Methoden der konventionellen wie der komplementären Medizin infrage. Bei den natürlichen Substanzen werden Interaktionen diskutiert. Sie betreffen aber auch Substanzen der konventionellen Medizin. Ziel der Analyse ist die Frage, inwieweit in klinischen Studien und Reviews zur supportiven Therapie potentielle Interaktionen berücksichtigt werden.

Material und Methodik: Mittels systematischer Recherche wurden klinische Studien und Reviews identifiziert und im Hinblick auf die Berücksichtigung möglicher Interaktionen analysiert. Ergebnisse: Es wurden 46 klinische Studien und ein Cochrane-Review erfasst. Von den 35 Studien zur konventionellen medikamentösen Therapie berücksichtigten 5 (14 %) evtl. Interaktionen. Von 17 Studien zur Komplementärmedizin waren es 2 Arbeiten (11,7 %). Das Cochrane-Review geht nicht auf Interaktionen ein. Diskussion: Für zukünftige Studien sollte bei nicht auszuschließender Interaktion eine Strategie zur Kontrolle der klinisch relevanten Folgen erarbeitet werden. Die Autoren schlagen hierfür Überlebens- und Rezidivdaten als sekundäre Endpunkte auch bei rein supportiven Therapiestudien als sinnvollen Ansatz vor. Die sich hieraus ergebenden Überlegungen für den Studienalltag werden im Artikel thematisiert.

Key words

breast cancer - antihormone therapy - hormone withdrawal signs - complementary medicine - interactions

Schlüsselwörter

Mammakarzinom - antihormonelle Therapie - Hormonentzugserscheinungen - Komplementärmedizin - Interaktionen

• References

• 1 Hadji P et al. Onkologie. Non-Compliance in der adjuvanten, endokrinen Therapie des Mammakarzinoms. Geburtsh Frauenheilk 2007; 67: 497
• 2 Brucker S. Onkologie. Postmenopause: adjuvante endokrine Therapie des frühen hormonrezeptorpositiven Mammakarzinoms. Geburtsh Frauenheilk 2008; 68: 847
• 3 Distler W et al. Unerwünschte gynäkologische und operative Interventionen bei der Behandlung des postmenopausalen Mammakarzinoms mit Anastrozol und Tamoxifen. Geburtsh Frauenheilk 2010; 70: 57
• 4 Bossart M et al. Frühes Mammakarzinom – Lebensqualität nach Switch von Tamoxifen auf Exemestan. Geburtsh Frauenheilk 2011; 71: 847
• 5 Sparreboom A et al. Herbal interactions in the United States: potential adverse interactions with anticancer agents. J Clin Oncol 2003; 22: 2489-2503
• 6 http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm%23background Stand: 30.8.2012
• 7 Zhang L et al. Drug interactions evaluation: an integrated part of risk assessment of therapeutics. Toxicol Appl Pharmacol 2010; 243: 134-145
• 8 Hu Z et al. St. Johnʼs wort modulates the toxicities and pharmacokinetics of CPT-11 (irinotecan) in rats. Pharm Res 2005; 22: 902-914
• 9 Barton D et al. Depomedroxyprogesterone acetate for hot flashes. J Pain Symptom Manage 2002; 24: 603-607
• 10 Barton DL et al. Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. J Clin Oncol 1998; 16: 495-500
• 11 Bertelli G et al. Intramuscular depot medroxyprogesterone versus oral megestrol for the control of postmenopausal hot flashes in breast cancer patients: a randomized study. Ann Oncol 2002; 13: 883-888
• 12 Biglia N et al. Non-hormonal treatment of hot flushes in breast cancer survivors: gabapentin vs. vitamin E. Climacteric 2009; 12: 310-318
• 13 Biglia N et al. Evaluation of low-dose venlafaxine hydrochloride for the therapy of hot flushes in breast cancer survivors. Maturitas 2005; 52: 78-85
• 14 Bordeleau L et al. Multicenter, randomized, cross-over clinical trial of venlafaxine versus gabapentin for the management of hot flashes in breast cancer survivors. J Clin Oncol 2010; 28: 5147-5152
• 15 Buijs C et al. Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: a double-blind, randomized cross-over study. Breast Cancer Res Treat 2009; 115: 573-580
• 16 Carpenter JS et al. Randomized, double-blind, placebo-controlled crossover trials of venlafaxine for hot flashes after breast cancer. Oncologist 2007; 12: 124-135
• 17 Carpenter JS et al. Evaluating the role of serotonin in hot flashes after breast cancer using acute tryptophan depletion. Menopause 2009; 16: 644-652
• 18 Clover A et al. Homeopathic treatment of hot flushes: a pilot study. Homeopathy 2002; 91: 75-79
• 19 Deng G et al. Randomized, controlled trial of acupuncture for the treatment of hot flashes in breast cancer patients. J Clin Oncol 2007; 25: 5584-5590
• 20 Dyer J et al. A study to look at the effects of a hydrolat spray on hot flushes in women being treated for breast cancer. Complement Ther Clin Pract 2008; 14: 273-279
• 21 Elkins G et al. Randomized trial of a hypnosis intervention for treatment of hot flashes among breast cancer survivors. J Clin Oncol 2008; 26: 5022-5026
• 22 Frisk J et al. Long-term follow-up of acupuncture and hormone therapy on hot flushes in women with breast cancer: a prospective, randomized, controlled multicenter trial. Climacteric 2008; 11: 166-174
• 23 Goldberg RM et al. Transdermal clonidine for ameliorating tamoxifen-induced hot flashes. J Clin Oncol 1994; 12: 155-158
• 24 Goodwin JW et al. Phase III randomized placebo-controlled trial of two doses of megestrol acetate as treatment for menopausal symptoms in women with breast cancer: Southwest Oncology Group Study 9626. J Clin Oncol 2008; 26: 1650-1656
• 25 Hernandez MG et al. Cimicifuga racemosa for the treatment of hot flushes in women surviving breast cancer. Maturitas 2003; 44 (Suppl. 01) S59-S65
• 26 Hervik J et al. Acupuncture for the treatment of hot flashes in breast cancer patients, a randomized, controlled trial. Breast Cancer Res Treat 2009; 116: 311-316
• 27 Jacobs J et al. Homeopathy for menopausal symptoms in breast cancer survivors: a preliminary randomized controlled trial. J Altern Complement Med 2005; 11: 21-27
• 28 Jacobson JS et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 2001; 19: 2739-2745
• 29 Joffe H et al. Augmentation of venlafaxine and selective serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer patients with hot flashes: a randomized, double-blind, placebo-controlled trial. Menopause 2010; 17: 908-916
• 30 Kenemans P et al. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol 2009; 10: 135-146
• 31 Kimmick GG et al. Randomized, double-blind, placebo-controlled, crossover study of sertraline (Zoloft) for the treatment of hot flashes in women with early stage breast cancer taking tamoxifen. Breast J 2006; 12: 114-122
• 32 Kroiss R et al. The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo-controlled trial. BJOG 2005; 112: 228-233
• 33 Lipov EG et al. Effects of stellate-ganglion block on hot flushes and night awakenings in survivors of breast cancer: a pilot study. Lancet Oncol 2008; 9: 523-532
• 34 Loibl S et al. Venlafaxine is superior to clonidine as treatment of hot flashes in breast cancer patients – a double-blind, randomized study. Ann Oncol 2007; 18: 689-693
• 35 Loprinzi CL et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet 2000; 356: 2059-2063
• 36 Loprinzi CL et al. Megestrol acetate for the prevention of hot flashes. N Engl J Med 1994; 331: 347-352
• 37 Loprinzi CL et al. Pilot evaluation of venlafaxine hydrochloride for the therapy of hot flashes in cancer survivors. J Clin Oncol 1998; 16: 2377-2381
• 38 Loprinzi CL et al. Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol 2002; 20: 1578-1583
• 39 MacGregor CA et al. A randomised double-blind controlled trial of oral soy supplements versus placebo for treatment of menopausal symptoms in patients with early breast cancer. Eur J Cancer 2005; 41: 708-714
• 40 Mariani L et al. Hot-flashes in breast cancer survivors: effectiveness of low-dosage fluoxetine. A pilot study. J Exp Clin Cancer Res 2005; 24: 373-378
• 41 Nikander E et al. Effects of phytoestrogens on bone turnover in postmenopausal women with a history of breast cancer. J Clin Endocrinol Metab 2004; 89: 1207-1212
• 42 Pandya KJ et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial. Lancet 2005; 366: 818-824
• 43 Pandya KJ et al. Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study. Ann Intern Med 2000; 132: 788-793
• 44 Pandya KJ et al. Pilot study using gabapentin for tamoxifen-induced hot flashes in women with breast cancer. Breast Cancer Res Treat 2004; 83: 87-89
• 45 Quella SK et al. Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial. J Clin Oncol 2000; 18: 1068-1074
• 46 Quella SK et al. Long term use of megestrol acetate by cancer survivors for the treatment of hot flashes. Cancer 1998; 82: 1784-1788
• 47 Rada G et al. Non-hormonal interventions for hot flushes in women with a history of breast cancer. Cochrane Database Syst Rev 2010; (9) CD004923
• 48 Stearns V et al. A pilot trial assessing the efficacy of paroxetine hydrochloride (Paxil) in controlling hot flashes in breast cancer survivors. Ann Oncol 2000; 11: 17-22
• 49 Stearns V et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol 2005; 23: 6919-6930
• 50 Thompson EA et al. A pilot, randomized, double-blinded, placebo-controlled trial of individualized homeopathy for symptoms of estrogen withdrawal in breast-cancer survivors. J Altern Complement Med 2005; 11: 13-20
• 51 Thompson S et al. Levetiracetam for the treatment of hot flashes: a phase II study. Support Care Cancer 2008; 16: 75-82
• 52 Van Patten CL et al. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol 2002; 20: 1449-1455
• 53 Walker EM et al. Acupuncture versus venlafaxine for the management of vasomotor symptoms in patients with hormone receptor-positive breast cancer: a randomized controlled trial. J Clin Oncol 2010; 28: 634-640
• 54 Weitzner MA et al. A pilot trial of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer. J Pain Symptom Manage 2002; 23: 337-345
• 55 Wu MF et al. The efficacy of sertraline for controlling hot flashes in women with or at high risk of developing breast cancer. Breast Cancer Res Treat 2009; 118: 369-375
• 56 Riechelmann RP et al. Drug interactions in oncology: how common are they?. Ann Oncol 2009; 20: 1907-1912
• 57 Haddad A et al. The pharmacological importance of cytochrome CYP3A4 in palliation of symptoms: review and recommendations for avoiding adverse drug interactions. Support Care Cancer 2007; 15: 251-257
• 58 Desmarais JE et al. Interactions between tamoxifen and antidepressants via cytochrome P450 2D6. J Clin Psychiatry 2009; 70: 1688-1697