Skip to main content
Top
Published in: BMC Neurology 1/2016

Open Access 01-12-2016 | Research article

The impact of paclitaxel and carboplatin chemotherapy on the autonomous nervous system of patients with ovarian cancer

Authors: Emmanouil V. Dermitzakis, Vasilios K. Kimiskidis, George Lazaridis, Zoi Alexopoulou, Eleni Timotheadou, Alexandros Papanikolaou, Ourania Romanidou, George Georgiadis, Konstantine T. Kalogeras, Iakovos Tsiptsios, Basil Tarlatzis, George Fountzilas

Published in: BMC Neurology | Issue 1/2016

Login to get access

Abstract

Background

Paclitaxel-based regimens are frequently associated with the development of peripheral neuropathy. The autonomous nervous system (ANS) effects, however, of this chemotherapeutic agent remain unexplored.

Methods

We investigated a group of 31 female patients with ovarian cancer receiving treatment with paclitaxel and carboplatin, as well as a group of 16 healthy age- and gender-matched healthy volunteers. All study participants completed a questionnaire and were assessed neurophysiologically at three time points (baseline, 3–4 months and 6–8 months following the onset of chemotherapy). The evaluation of the ANS included assessment of the adrenergic cardiovascular function (orthostatic hypotension-OH), parasympathetic heart innervation (30/15 ratio) and sympathetic skin response (SSR).

Results

At the 3–4 months ANS assessment, 19.2 % of the patients had systolic OH and the same percentage had diastolic OH, but at the 6–8 months evaluation no patient had systolic OH and only 13.8 % had diastolic OH. The values of the 30/15 ratio were significantly reduced at both time points, whereas the SSR was not affected.

Conclusions

Combined paclitaxel and carboplatin chemotherapy is associated with significant effects on the parasympathetic heart innervation and occasionally with effects on the adrenergic cardiovascular reaction. The SSR remained unaffected. Physicians should be alert to the possibility of these treatment-emergent side effects, so as to monitor ANS parameters and introduce treatment modifications accordingly. Our findings however, should be validated in larger cohorts.
Appendix
Available only for authorised users
Literature
1.
go back to reference Argyriou AA, Bruna J, Marmiroli P, Cavaletti G. Chemotherapy-induced peripheral neurotoxicity (CIPN): an update. Crit Rev Oncol Hematol. 2012;82(1):51–77.CrossRefPubMed Argyriou AA, Bruna J, Marmiroli P, Cavaletti G. Chemotherapy-induced peripheral neurotoxicity (CIPN): an update. Crit Rev Oncol Hematol. 2012;82(1):51–77.CrossRefPubMed
2.
go back to reference Lee JJ, Swain SM. Peripheral neuropathy induced by microtubule-stabilizing agents. J Clin Oncol. 2006;24(10):1633–42.CrossRefPubMed Lee JJ, Swain SM. Peripheral neuropathy induced by microtubule-stabilizing agents. J Clin Oncol. 2006;24(10):1633–42.CrossRefPubMed
3.
go back to reference Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC. Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol. 1993;20(4 Suppl 3):1–15.PubMed Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC. Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol. 1993;20(4 Suppl 3):1–15.PubMed
4.
go back to reference Lipton RB, Apfel SC, Dutcher JP, Rosenberg R, Kaplan J, Berger A, Einzig AI, Wiernik P, Schaumburg HH. Taxol produces a predominantly sensory neuropathy. Neurology. 1989;39(3):368–73.CrossRefPubMed Lipton RB, Apfel SC, Dutcher JP, Rosenberg R, Kaplan J, Berger A, Einzig AI, Wiernik P, Schaumburg HH. Taxol produces a predominantly sensory neuropathy. Neurology. 1989;39(3):368–73.CrossRefPubMed
5.
go back to reference Fountzilas G, Tsavdaridis D, Kalogera-Fountzila A, Christodoulou CH, Timotheadou E, Kalofonos CH, Kosmidis P, Adamou A, Papakostas P, Gogas H, et al. Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with advanced breast cancer. A Hellenic Cooperative Oncology Group phase II study. Ann Oncol. 2001;12(11):1545–51.CrossRefPubMed Fountzilas G, Tsavdaridis D, Kalogera-Fountzila A, Christodoulou CH, Timotheadou E, Kalofonos CH, Kosmidis P, Adamou A, Papakostas P, Gogas H, et al. Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with advanced breast cancer. A Hellenic Cooperative Oncology Group phase II study. Ann Oncol. 2001;12(11):1545–51.CrossRefPubMed
6.
go back to reference Seidman AD, Hudis CA, Albanell J, Tong W, Tepler I, Currie V, Moynahan ME, Theodoulou M, Gollub M, Baselga J, et al. Dose-dense therapy with weekly 1-h paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol. 1998;16(10):3353–61.PubMed Seidman AD, Hudis CA, Albanell J, Tong W, Tepler I, Currie V, Moynahan ME, Theodoulou M, Gollub M, Baselga J, et al. Dose-dense therapy with weekly 1-h paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol. 1998;16(10):3353–61.PubMed
7.
go back to reference Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2001;19(22):4216–23.PubMed Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2001;19(22):4216–23.PubMed
9.
go back to reference Dermitzakis EV, Kimiskidis VK, Eleftheraki A, Lazaridis G, Konstantis A, Basdanis G, Tsiptsios I, Georgiadis G, Fountzilas G. The impact of oxaliplatin-based chemotherapy for colorectal cancer on the autonomous nervous system. Eur J Neurol. 2014;21(12):1471–7.CrossRefPubMed Dermitzakis EV, Kimiskidis VK, Eleftheraki A, Lazaridis G, Konstantis A, Basdanis G, Tsiptsios I, Georgiadis G, Fountzilas G. The impact of oxaliplatin-based chemotherapy for colorectal cancer on the autonomous nervous system. Eur J Neurol. 2014;21(12):1471–7.CrossRefPubMed
10.
go back to reference Kaufmann H. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure and multiple system atrophy. Clin Auton Res. 1996;6(2):125–6.CrossRefPubMed Kaufmann H. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure and multiple system atrophy. Clin Auton Res. 1996;6(2):125–6.CrossRefPubMed
11.
go back to reference Assessment: Clinical autonomic testing report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 1996;46(3):873–80. Assessment: Clinical autonomic testing report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 1996;46(3):873–80.
12.
go back to reference Mc NQ. Note on the sampling error of the difference between correlated proportions or percentages. Psychometrika. 1947;12(2):153–7.CrossRef Mc NQ. Note on the sampling error of the difference between correlated proportions or percentages. Psychometrika. 1947;12(2):153–7.CrossRef
13.
go back to reference Wilcoxon F. Individual comparisons by ranking methods. Biom Bull. 1945;1(6):80–3.CrossRef Wilcoxon F. Individual comparisons by ranking methods. Biom Bull. 1945;1(6):80–3.CrossRef
14.
go back to reference Mann HW, Whitney DR. On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other. Ann Math Stat. 1947;18(1):50–60.CrossRef Mann HW, Whitney DR. On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other. Ann Math Stat. 1947;18(1):50–60.CrossRef
16.
go back to reference Pentassuglia L, Timolati F, Seifriz F, Abudukadier K, Suter TM, Zuppinger C. Inhibition of ErbB2/neuregulin signaling augments paclitaxel-induced cardiotoxicity in adult ventricular myocytes. Exp Cell Res. 2007;313(8):1588–601.CrossRefPubMed Pentassuglia L, Timolati F, Seifriz F, Abudukadier K, Suter TM, Zuppinger C. Inhibition of ErbB2/neuregulin signaling augments paclitaxel-induced cardiotoxicity in adult ventricular myocytes. Exp Cell Res. 2007;313(8):1588–601.CrossRefPubMed
17.
go back to reference Nistico C, Bria E, Cuppone F, Carpino A, Ferretti G, Vitelli G, Sperduti I, Calabretta F, Toglia G, Tomao S, et al. Troponin-T and myoglobin plus echocardiographic evaluation for monitoring early cardiotoxicity of weekly epirubicin-paclitaxel in metastatic breast cancer patients. Anti-Cancer Drugs. 2007;18(2):227–32.CrossRefPubMed Nistico C, Bria E, Cuppone F, Carpino A, Ferretti G, Vitelli G, Sperduti I, Calabretta F, Toglia G, Tomao S, et al. Troponin-T and myoglobin plus echocardiographic evaluation for monitoring early cardiotoxicity of weekly epirubicin-paclitaxel in metastatic breast cancer patients. Anti-Cancer Drugs. 2007;18(2):227–32.CrossRefPubMed
18.
go back to reference Gennari A, Salvadori B, Donati S, Bengala C, Orlandini C, Danesi R, Del Tacca M, Bruzzi P, Conte PF. Cardiotoxicity of epirubicin/paclitaxel-containing regimens: role of cardiac risk factors. J Clin Oncol. 1999;17(11):3596–602.PubMed Gennari A, Salvadori B, Donati S, Bengala C, Orlandini C, Danesi R, Del Tacca M, Bruzzi P, Conte PF. Cardiotoxicity of epirubicin/paclitaxel-containing regimens: role of cardiac risk factors. J Clin Oncol. 1999;17(11):3596–602.PubMed
19.
go back to reference Biganzoli L, Cufer T, Bruning P, Coleman RE, Duchateau L, Rapoport B, Nooij M, Delhaye F, Miles D, Sulkes A, et al. Doxorubicin-paclitaxel: a safe regimen in terms of cardiac toxicity in metastatic breast carcinoma patients. Results from a European Organization for Research and Treatment of Cancer multicenter trial. Cancer. 2003;97(1):40–5.CrossRefPubMed Biganzoli L, Cufer T, Bruning P, Coleman RE, Duchateau L, Rapoport B, Nooij M, Delhaye F, Miles D, Sulkes A, et al. Doxorubicin-paclitaxel: a safe regimen in terms of cardiac toxicity in metastatic breast carcinoma patients. Results from a European Organization for Research and Treatment of Cancer multicenter trial. Cancer. 2003;97(1):40–5.CrossRefPubMed
20.
go back to reference Gehl J, Boesgaard M, Paaske T, Vittrup Jensen B, Dombernowsky P. Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Ann Oncol. 1996;7(7):687–93.CrossRefPubMed Gehl J, Boesgaard M, Paaske T, Vittrup Jensen B, Dombernowsky P. Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Ann Oncol. 1996;7(7):687–93.CrossRefPubMed
21.
go back to reference Salvatorelli E, Menna P, Cascegna S, Liberi G, Calafiore AM, Gianni L, Minotti G. Paclitaxel and docetaxel stimulation of doxorubicinol formation in the human heart: implications for cardiotoxicity of doxorubicin-taxane chemotherapies. J Pharmacol Exp Ther. 2006;318(1):424–33.CrossRefPubMed Salvatorelli E, Menna P, Cascegna S, Liberi G, Calafiore AM, Gianni L, Minotti G. Paclitaxel and docetaxel stimulation of doxorubicinol formation in the human heart: implications for cardiotoxicity of doxorubicin-taxane chemotherapies. J Pharmacol Exp Ther. 2006;318(1):424–33.CrossRefPubMed
22.
go back to reference Minotti G, Saponiero A, Licata S, Menna P, Calafiore AM, Teodori G, Gianni L. Paclitaxel and docetaxel enhance the metabolism of doxorubicin to toxic species in human myocardium. Clin Cancer Res. 2001;7(6):1511–5.PubMed Minotti G, Saponiero A, Licata S, Menna P, Calafiore AM, Teodori G, Gianni L. Paclitaxel and docetaxel enhance the metabolism of doxorubicin to toxic species in human myocardium. Clin Cancer Res. 2001;7(6):1511–5.PubMed
23.
go back to reference Altin C, Sade LE, Demirtas S, Karacaglar E, Kanyilmaz S, Simsek V, Ayhan A, Muderrisoglu H. Effects of Paclitaxel and Carboplatin combination on mechanical myocardial and microvascular functions: a transthoracic Doppler echocardiography and two-dimensional strain imaging study. Echocardiography. 2015;32(2):238–47.CrossRefPubMed Altin C, Sade LE, Demirtas S, Karacaglar E, Kanyilmaz S, Simsek V, Ayhan A, Muderrisoglu H. Effects of Paclitaxel and Carboplatin combination on mechanical myocardial and microvascular functions: a transthoracic Doppler echocardiography and two-dimensional strain imaging study. Echocardiography. 2015;32(2):238–47.CrossRefPubMed
24.
go back to reference Sasaki H, Yano M, Kawano O, Hikosaka Y, Fujii Y. Thymoma associated with fatal myocarditis and polymyositis in a 58-year-old man following treatment with carboplatin and paclitaxel: A case report. Oncol Lett. 2012;3(2):300–2.PubMed Sasaki H, Yano M, Kawano O, Hikosaka Y, Fujii Y. Thymoma associated with fatal myocarditis and polymyositis in a 58-year-old man following treatment with carboplatin and paclitaxel: A case report. Oncol Lett. 2012;3(2):300–2.PubMed
25.
go back to reference Haj Mohammad N, Kamphuis M, Hulshof MC, Lutkenhaus LJ, Gisbertz SS, Bergman JJ, de Bruin-Bon HA, Geijsen ED, Bel A, Boekholdt SM, et al. Reduction of heart volume during neoadjuvant chemoradiation in patients with resectable esophageal cancer. Radiother Oncol. 2015;114(1):91–5.CrossRefPubMed Haj Mohammad N, Kamphuis M, Hulshof MC, Lutkenhaus LJ, Gisbertz SS, Bergman JJ, de Bruin-Bon HA, Geijsen ED, Bel A, Boekholdt SM, et al. Reduction of heart volume during neoadjuvant chemoradiation in patients with resectable esophageal cancer. Radiother Oncol. 2015;114(1):91–5.CrossRefPubMed
26.
go back to reference Sener HO, Tascilar NF, Balaban H, Selcuki D. Sympathetic skin response in carpal tunnel syndrome. Clin Neurophysiol. 2000;111(8):1395–9.CrossRefPubMed Sener HO, Tascilar NF, Balaban H, Selcuki D. Sympathetic skin response in carpal tunnel syndrome. Clin Neurophysiol. 2000;111(8):1395–9.CrossRefPubMed
Metadata
Title
The impact of paclitaxel and carboplatin chemotherapy on the autonomous nervous system of patients with ovarian cancer
Authors
Emmanouil V. Dermitzakis
Vasilios K. Kimiskidis
George Lazaridis
Zoi Alexopoulou
Eleni Timotheadou
Alexandros Papanikolaou
Ourania Romanidou
George Georgiadis
Konstantine T. Kalogeras
Iakovos Tsiptsios
Basil Tarlatzis
George Fountzilas
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2016
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-016-0710-4

Other articles of this Issue 1/2016

BMC Neurology 1/2016 Go to the issue