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Use of Guarana for Hot Flashes after Breast Cancer: Randomized, Double-Blind, Placebo-Controlled Phase II Trial


Affiliations
1 (School of Medicine of the ABC Foundation), AV Lauro Gomes, 2000, Santo Andre, SP - 09060-870, Brazil
 

Background: Hot flashes are common in menopausal women and significantly affect the quality of life of many patients diagnosed with breast cancer for which hormone replacement therapy is not indicated. In a previous uncontrolled study, guarana (Paullinia cupana) showed significant decreases in the amount and intensity of hot flashes in this group of women. Hypothesis/Purpose: The main objective was to reduce the intensity and frequency of hot flashes with the use of PC-18, compared with placebo in women who survived breast cancer without current evidence of disease. Study Design: The present study consists of a double-blind, randomized, placebo-controlled, uni-institutional, two-arm phase II clinical trial. Methods: The experimental group received the purified dry extract of Paullinia cupana (PC-18) at a dose of 37.5 g twice daily, while the other group received placebo, also twice daily. Results: The study included 40 patients who had completed surgical, chemotherapeutic and/or radiotherapeutic treatment for more than 3 months and who were on adjuvant hormone therapy at the time of inclusion, 20 in each arm. Both groups showed significant reductions in the number and intensity of hot flashes, with no significant difference between the arms. There was a higher intensity and frequency of hot flashes in patients receiving tamoxifen compared with those who received aromatase inhibitors. The toxicities observed were not very significant. Conclusion: This concludes that PC-18 did not demonstrate significantly greater capacity than placebo for control of hot flashes in women with a history of breast cancer and adjuvant hormone therapy.

Keywords

Breast Neoplasia, Guarana, Hot Flashes, Paullinia cupana.
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  • Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC. The European organization for research and treatment of cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology. J. Natl Cancer Inst. 1993; 85:365–76. PMid: 8433390. https://doi.org/10.1093/jnci/85.5.365
  • Andersen O, Engebretsen T, Solberg VM, Orbo A. α-Methyldopa for climacteric hot flushes: A double-blind, randomized, cross-over study. Acta Obstet Gynecol Scand. 1986; 65:405–9. PMid: 3535358. https://doi.org/10.3109/00016348609157373
  • Andrade L, Gorenstein C, Filho AHV, Tung TC, Artes R. Psychometric properties of the Portuguese version of the State-Trait Anxiety Inventory applied to college students: Factor analysis and relation to the Beck Depression Inventory. Braz J Med Biol Res. 2001; 34:367–74. PMid: 11262588. https://doi.org/10.1590/S0100-879X2001000300011
  • Beck AT, Steer RA. Internal consistencies of the original and revised beck depression inventory. J Clin Psychol. 1984; 40:1365–7. https://doi.org/10.1002/1097-4679(198411)40:6 < 1365::AID-JCLP2270400615>3.0.CO;2-D
  • Berry DA, Cronin KA, Plevriti, SK, Fryback DG, Clarke L, Zelen M, Mandelblatt JS, Yakovlev AY, Habbema JDF, Feuer EJ. Effect of screening and adjuvant therapy on mortality from breast cancer. New Engl J Med. 2005; 353:1784–92. PMid: 16251534. https://doi.org/10.1056/NEJMoa050518
  • Buijs C, Mom CH, Willemse PHB, Boezen HM, Maurer JM, Wymenga ANM, de Jong RS, Nieboer P, de Vries EGE, Mourits MJE. Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: A double-blind, randomized cross-over study. Breast Cancer Res Treat. 2008; 115:573–80. PMid18670875. https://doi.org/10.1007/s10549-008-0138-7
  • Butt DA, Lock M, Lewis JE, Ross S, Moineddin R. Gabapentin for the treatment of menopausal hot flashes: A randomized controlled trial. Menopause. 2008; 15:310–8. PMid: 17917611. https://doi.org/10.1097/gme.0b013e3180dca175
  • Campos MP, Riechelmann R, Martins LC, Hassan BJ, Casa FB, Del Giglio A. Effect of guarana (Paullinia cupana) on fatigue in breast cancer patients undergoing systemic chemotherapy. J Clin Oncol. 2010; 28:9007. https://doi.org/10.1200/jco.2010.28.15_suppl.9007
  • Carpenter JS. The hot flash related daily interference scale: A tool for assessing the impact of hot flashes on quality of life following breast cancer. J Pain Symptom Manag. 2001; 22:979–89. https://doi.org/10.1016/S0885-3924(01)00353-0
  • Carpenter JS, Johnson DH, Wagner LJ, Andrykowski MA. Hot flashes and related outcomes in breast cancer survivors and matched comparison women. Oncol Nurs Forum. 2002; 29:E16–25. PMid: 11979290. https://doi.org/10.1188/02.ONF.E16-E25
  • Carpenter JS, Storniolo AM, Johns S, Monahan PO, Azzouz F, Elam JL, Johnson CS, Shelton RC. Randomized, double-blind, placebo-controlled crossover trials of venlafaxine for hot flashes after breast cancer. Oncologist. 2007; 12:124–35. PMid: 17227907. https://doi.org/10.1634/theoncologist.12-1-124
  • Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, Wallace EP. Development of a fatigue scale. J Psychosom Res. 1993; 37:147–53. https://doi.org/10.1016/0022-3999(93)90081-P
  • CTCAE versão 4.0. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm.
  • Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), 2005. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet. 2005; 365:1687– 717. https://doi.org/10.1016/S0140-6736(05)66544-0
  • Espinola EB, Dias RF, Mattei R, Carlini EA. Pharmacological activity of Guarana (Paullinia cupana Mart.) in laboratory animals. J Ethnopharmacol. 1997; 55:223–9. https://doi.org/10.1016/S0378-8741(96)01506-1
  • Evans ML, Pritts E, Vittinghoff E, McClish K, Morgan KS, Jaffe RB. Management of postmenopausal hot flushes with venlafaxine hydrochloride: A randomized, controlled trial.Obstet. Gynecol. 2005; 105:161–6. PMid: 15625158. https://doi.org/10.1097/01.AOG.0000147840.06947.46
  • Ganz PA, Desmond KA, Leedham B, Rowland JH, Meyerowitz BE, Belin TR. Quality of life in long-term, disease-free survivors of breast cancer: A follow-up study. J Natl Cancer Inst. 2002; 94:39–49. PMid: 11773281. https://doi.org/10.1093/jnci/94.1.39
  • Goodwin JW, Green SJ, Moinpour CM, Bearden JD, Giguere JK, Jiang CS, Lippman SM, Martino S, Albain KS. 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; 26:1650–6. PMid: 18375894. https://doi.org/10.1200/JCO.2006.10.6179
  • Guttuso T, Kurlan R, McDermott MP, Kieburtz K. Gabapentinʼs effects on hot flashes in postmenopausal women: A randomized controlled trial. Obstet Gynecol. 2003; 101:337–45. https://doi.org/10.1016/S0029-7844(02)02712-6
  • Instituto Nacional de Cancer Jose Alencar Gomes da Silva. Estimativa 2018: Incidencia de Cancer no Brasil. INCA, Rio de Janeiro. 2018.
  • Jin Y, Hayes DF, Li L, Robarge JD, Skaar TC, Philips S, Nguyen A, Schott A, Hayden J, Lemler S, Storniolo AM, Flockhart DA, Stearns V. Estrogen receptor genotypes influence hot flash prevalence and composite score before and after tamoxifen therapy. J Clin Oncol. 2008; 26:5849–54. PMid: 19018086 PMCid: PMC2645113. https://doi.org/10.1200/JCO.2008.16.8377
  • Jones SE, Cantrell J, Vukelja S, Pippen J, O’Shaughnessy J, Blum JL, Brooks R, Hartung NL, Negron AG, Richards DA, Rivera R, Holmes FA, Chittoor S, Whittaker TL, Bordelon JH, Ketchel SJ, Davis JC, Ilegbodu D, Kochis J, Asmar L. Comparison of menopausal symptoms during the first year of adjuvant therapy with either exemestane or tamoxifen in early breast cancer: Report of a tamoxifen exemestane adjuvant multicenter trial substudy. J Clin Oncol. 2007; 25:4765–71. PMid: 17947724. https://doi.org/10.1200/JCO.2007.10.8274
  • Kagan R, Constantine G, Olivier S. Treatment with Desvenlafaxine Succinate (DVS) results in a sustained reduction in number of severe Hot Flushes (HFs) in menopausal women. Menopause. 2007; 14:1084–4.
  • Kawamura T, Sobue T. Comparison of breast cancer mortality in five countries: France, Italy, Japan, the UK and the USA from the WHO mortality database (1960-2000). Jpn J Clin Oncol. 2005; 35:758–9. PMid. 16377739. https://doi.org/10.1093/jjco/hyi201
  • Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL, Novotny PJ, Dakhil SR, Rodger K, Rummans TA, Christensen BJ. Venlafaxine in management of hot flashes in survivors of breast cancer: A randomised controlled trial. Lancet. 2000; 356:2059–63. https://doi.org/10.1016/S0140-6736(00)03403-6
  • Loprinzi CL, Sloan JA, Perez EA, Quella SK, Stella PJ, Mailliard JA, Halyard MY, Pruthi S, Novotny PJ, Rummans TA. Phase III evaluation of fluoxetine for treatment of hot flashes. J Cli. Oncol. 2002; 20:1578–83. PMid: 11896107. https://doi.org/10.1200/JCO.2002.20.6.1578
  • Mathias C, Athanazio RA, Braghiroli MI, Nu-ez G, Lessa R, Macedo G, Sena EPD, Del Giglio A. Uso da escala de experiencia sexual do Arizona (ASEX) na avaliacao de disfuncao sexual em pacientes oncologicos brasileiros. J Bras Psiquiatr. 2005; 54:216–20.
  • McGahuey CA, Gelenberg AJ, Laukes CA, Moreno FA, Delgado PL, McKnight KM, Manber R. The Arizona sexual experience scale (ASEX): Reliability and validity. J Sex Marital Ther. 2000; 26:25–40. PMid: 10693114. https://doi.org/10.1080/009262300278623
  • Miranda MV, Metzner BS. Paullinia cupana: Revisao da materia medica. Rev Homeopat. 2010; 73:1–17.
  • Morrow PKH, Mattair DN, Hortobagyi GN. Hot flashes: A review of pathophysiology and treatment modalities. Oncologist. 2011; 16:1658–64. PMid: 22042786 PMCid: PMC3233302. https://doi.org/10.1634/theoncologist.2011-0174
  • Mortimer JE, Boucher L, Baty J, Knapp DL, Ryan E, Rowland JH. Effect of tamoxifen on sexual functioning in patients with breast cancer. J Clin Oncol. 1999; 17:1488–8. PMid: 10334535. https://doi.org/10.1200/JCO.1999.17.5.1488 32. NCCN Guidelines version 3, 2017. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
  • Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes: Scientific review. JAMA. 2004; 291:1610–20. https://doi.org/10.1001/jama.291.13.1610
  • Nesheim BI, Stre T. Reduction of menopausal hot flushes by methyldopa: A double blind crossover trial. Eur J Clin Pharmacol. 1981; 20:413–6. PMid: 7026262. https://doi.org/10.1007/BF00542092
  • Oliveira SS, del Giglio AB, Lerner TG, Zanellato RM, Tiemi L, Reifur L, Santi PX, del Giglio A. Paullinia cupana for control of hot flashes in breast cancer patients: A pilot study. Einstein. 2013; 11:435–8. PMCid: PMC4880378. https://doi.org/10.1590/S1679-45082013000400005
  • Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, Kamby C, Kjaer M, Gadeberg CC, Rasmussen BB, Blichert-Toft M, Mouridsen HT. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish breast cancer cooperative group DBCG 82c randomised trial. Lancet. 1999; 353:1641– 8. https://doi.org/10.1016/S0140-6736(98)09201-0
  • Pachman DR, Jones JM, Loprinzi CL. Management of menopause-associated vasomotor symptoms: Current treatment options, challenges and future directions. Int J Womens Health. 2010; 2:123–35. PMid: 21072305 PMCid: PMC2971731.
  • Pandya KJ, Morrow GR, Roscoe JA, Zhao H, Hickok JT, Pajon E, Sweeney TJ, Banerjee TK, Flynn PJ. Gabapentin for hot flashes in 420 women with breast cancer: A randomised double-blind placebo-controlled trial. Lancet. 2005; 366:818– 24. https://doi.org/10.1016/S0140-6736(05)67215-7
  • Pandya KJ, Raubertas RF, Flynn PJ, Hynes HE, Rosenbluth RJ, Kirshner JJ, Pierce HI, Dragalin V, Morrow GR. 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; 132:788–93. PMid: 10819701. https://doi.org/10.7326/0003-4819-132-10-200005160-00004
  • Peto R, Boreham J, Clarke M, Davies C, Beral V. UK and USA breast cancer deaths down 25% in year 2000 at ages 20–69 years. Lancet. 2000; 355:1822. https://doi.org/10.1016/S0140-6736(00)02277-7
  • Santen RJ, Stuenkel CA, Davis SR, Pinkerton JV, Gompel A, Lumsden MA. Managing menopausal symptoms and associated clinical issues in breast cancer survivors. J Clin Endocrinol Metab. 2017; 102:3647–61. PMid: 28934376. https://doi.org/10.1210/jc.2017-01138
  • Sloan JA, Loprinzi CL, Novotny PJ, Barton DL, Lavasseur BI, Windschitl H. Methodologic lessons learned from hot flash studies. J Clin Oncol. 2001; 19:4280–90. PMid: 11731510. https://doi.org/10.1200/JCO.2001.19.23.4280
  • Soares HP, Zatta SM, Bezerra AS, Wroclawski ML, Pertusier LO, Giglio A. Aplicacao dos questionarios de qualidade de vida ‘’FLIE’’ e ‘’EORTC QLQ C-30’’ para pacientes oncologicos em tratamento quimioterapico: Estudo piloto da Disciplina de Oncologia e Hematologia da Faculdade de Medicina da Fundacao ABC. Rev Soc Bras Cancerol. 2001; 15:19.
  • Speroff L, Gass M, Constantine G, Olivier S, Study 315 Investigators. Efficacy and tolerability of desvenlafaxine succinate treatment for menopausal vasomotor symptoms: A randomized controlled trial. Obstet Gynecol. 2008l 111:77–87. PMid: 18165395. https://doi.org/10.1097/01.AOG.0000297371.89129.b3
  • Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: A randomized controlled trial. JAMA. 2003; 289:2827–34. PMid: 12783913. https://doi.org/10.1001/jama.289.21.2827
  • Tfouni SAV, Camargo MCR, Vitorino SHP, Menegario TF, Toledo MCDF. Contribuicao do guarana em po (Paullinia cupana) como fonte de cafeína na dieta. Rev Nutr. 2007; 20:63–8. https://doi.org/10.1590/S1415-52732007000100007
  • Thurston RC, Sutton-Tyrrell K, Everson-Rose SA, Hess R, Matthews KA. Hot flashes and subclinical cardiovascular disease: Findings from the study of women’s health across the nation heart study. Circulation. 2008; 118:1234–40. PMid: 18765392 PMCid: PMC2728044. https://doi.org/10.1161/CIRCULATIONAHA.108.776823
  • Weckerle CS, Stutz MA, Baumann TW. Purine alkaloids in Paullinia. Phytochemistry. 2003; 64:735–42. https://doi.org/10.1016/S0031-9422(03)00372-8
  • Young-McCaughan S. Sexual functioning in women with breast cancer after treatment with adjuvant therapy. Cancer Nurs. 1996; 19:308–19. PMid: 8768689. https://doi.org/10.1097/00002820-199608000-00007

Abstract Views: 313

PDF Views: 153




  • Use of Guarana for Hot Flashes after Breast Cancer: Randomized, Double-Blind, Placebo-Controlled Phase II Trial

Abstract Views: 313  |  PDF Views: 153

Authors

Abna Faustina de Sousa Vieira
(School of Medicine of the ABC Foundation), AV Lauro Gomes, 2000, Santo Andre, SP - 09060-870, Brazil
Vitor Augusto Queiroz Mauad
(School of Medicine of the ABC Foundation), AV Lauro Gomes, 2000, Santo Andre, SP - 09060-870, Brazil
Daniel Cubero
(School of Medicine of the ABC Foundation), AV Lauro Gomes, 2000, Santo Andre, SP - 09060-870, Brazil
Patrícia Xavier Santi
(School of Medicine of the ABC Foundation), AV Lauro Gomes, 2000, Santo Andre, SP - 09060-870, Brazil
Auro del Giglio
(School of Medicine of the ABC Foundation), AV Lauro Gomes, 2000, Santo Andre, SP - 09060-870, Brazil

Abstract


Background: Hot flashes are common in menopausal women and significantly affect the quality of life of many patients diagnosed with breast cancer for which hormone replacement therapy is not indicated. In a previous uncontrolled study, guarana (Paullinia cupana) showed significant decreases in the amount and intensity of hot flashes in this group of women. Hypothesis/Purpose: The main objective was to reduce the intensity and frequency of hot flashes with the use of PC-18, compared with placebo in women who survived breast cancer without current evidence of disease. Study Design: The present study consists of a double-blind, randomized, placebo-controlled, uni-institutional, two-arm phase II clinical trial. Methods: The experimental group received the purified dry extract of Paullinia cupana (PC-18) at a dose of 37.5 g twice daily, while the other group received placebo, also twice daily. Results: The study included 40 patients who had completed surgical, chemotherapeutic and/or radiotherapeutic treatment for more than 3 months and who were on adjuvant hormone therapy at the time of inclusion, 20 in each arm. Both groups showed significant reductions in the number and intensity of hot flashes, with no significant difference between the arms. There was a higher intensity and frequency of hot flashes in patients receiving tamoxifen compared with those who received aromatase inhibitors. The toxicities observed were not very significant. Conclusion: This concludes that PC-18 did not demonstrate significantly greater capacity than placebo for control of hot flashes in women with a history of breast cancer and adjuvant hormone therapy.

Keywords


Breast Neoplasia, Guarana, Hot Flashes, Paullinia cupana.

References





DOI: https://doi.org/10.18311/jnr%2F2019%2F22737