The impact of paclitaxel and carboplatin chemotherapy on the autonomous nervous system of patients with ovarian cancer (+heart systems)

sen·so·ri·mo·tor

ˌsen(t)sərēˈmōdər/adjective

Physiology adjective: sensorimotor (of nerves or their actions) having or involving both sensory and motor functions or pathways.

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open access - | BMC Neurology | Full Text
October 1, 2016

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.

Background

Paclitaxel is commonly used as first-line chemotherapy for advanced ovarian cancer and as adjuvant treatment, in combination with cisplatin or carboplatin, for residual disease. Taxanes (paclitaxel and docetaxel) are associated with numerous side effects, particularly including neurotoxic phenomena [1] . For instance, severe peripheral neuropathy is known to occur in patients receiving cumulative doses of around 1000 mg/m² paclitaxel and 400 mg/m² docetaxel [2]. In recent years, research interest focused on maximizing the therapeutic efficacy of paclitaxel, while minimizing the associated side effects. Despite these efforts, primarily sensory and occasionally sensorimotor [3, 4] peripheral neuropathy occurs in 59 to 78 % of treated patients [5, 6, 7].

Generalized peripheral neuropathies are frequently accompanied by autonomous nervous system (ANS) dysfunction [8]. However, it is currently unknown whether paclitaxel or its combination with carboplatin affects the ANS and whether paclitaxel-induced neuropathy comprises autonomic phenomena, as well.

The present study was designed to address this issue and investigate the effects of the combination of paclitaxel and carboplatin chemotherapy on the ANS. From a clinical point of view, paclitaxel is occasionally associated with hypotension, bradycardia and hypertension. Accordingly, we investigated the impact of paclitaxel on the sympathetic and parasympathetic innervation of the heart....

 Conclusions

The present study highlights the fact that combined paclitaxel and carboplatin chemotherapy for ovarian cancer is associated with significant effects on the sympathetic and parasympathetic heart innervation, whereas the SSR remains relatively untouched. Physicians caring for patients with ovarian cancer should be alert to the possibility of these treatment-emergent side effects, so as to monitor ANS parameters (BP, cardiac rhythm and their alterations upon standing) and introduce treatment modifications accordingly. Our findings however, should be validated in larger cohorts.

Abbreviations

ANS: 

Autonomous nervous system

BP: 

Blood pressure

DBP: 

Diastolic blood pressure

NCVs: 

Nerve conduction velocities

OH: 

Orthostatic hypotension

OS: 

Overall survival

PFS: 

Progression-free survival

SBP: 

Systolic blood pressure

SD: 

Standard deviation

SSR: 

Sympathetic skin response