Long-term neurotoxicity and Raynaud's phenomenon in patients treated with cisplatin-based chemotherapy for malignant ovarian germ cell tumor

Acta Obstet Gynecol Scand. 2019 Feb;98(2):240-249. doi: 10.1111/aogs.13477. Epub 2018 Nov 22.

Abstract

Introduction: The aim was to evaluate "overall neuropathy", defined as peripheral paresthesia and Raynaud's phenomenon, in long-term survivors of malignant ovarian germ cell tumors (MOGCTs) treated with cisplatin-based chemotherapy (CBCT).

Material and methods: Ninety-three MOGCT survivors recorded in Norway in 1980-2009 (median follow up: 15 years) were included in this analysis. Forty-nine received CBCT (CBCT group) and 44 received other or no chemotherapy (non-CBCT group). Applying the scale for chemotherapy-induced neurotoxicity, the prevalence of overall neuropathy (ie score >1 on a 0-3 scale) was compared between the two groups. Forty women from the CBCT group also underwent neurophysiological and neurological examinations; results from the neurological examination were graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Effects version 4 (NCI-CTCAE scale v4). These women were then categorized into subgroups of low (≤3 cycles of CBCT, n = 23) and high CBCT (≥4 cycles of CBCT, n = 17).

Results: Twenty-eight (57%) women from the CBCT group reported overall neuropathy, compared with 20 (45%) in the non-CBCT group (P = .06). Of the 40 MOGCT survivors in the CBCT group who underwent neurophysiological and neurological examinations, 14 (35%) showed NCI-CTCAE grade ≥1 signs or symptoms of peripheral neuropathy. Pathological findings of NCI-CTCAE grade 2 or 3 signs or symptoms were found in four survivors (10%) from the high CBCT subgroup, all of whom also showed objective signs of neuropathy.

Conclusions: Though about half of our MOGCT survivors reported overall neuropathy after CBCT, more severe pathological neurological/neurophysiological findings that impacted daily living were recorded in only 10% of them. Our observations of a similar prevalence of self-reported overall neuropathy in the CBCT and non-CBCT group, combined with limited objective neurological findings, warrant further study to increase the understanding of the specific pathophysiological pathways of long-term CBCT-induced neuropathy.

Keywords: Raynaud's phenomenon; cisplatin-based chemotherapy; malignant ovarian germ cell tumors; neuropathy; peripheral paresthesia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cancer Survivors
  • Cisplatin* / administration & dosage
  • Cisplatin* / adverse effects
  • Female
  • Humans
  • Long Term Adverse Effects / diagnosis
  • Long Term Adverse Effects / epidemiology
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal / drug therapy*
  • Neoplasms, Germ Cell and Embryonal / epidemiology
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Norway / epidemiology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / pathology
  • Paresthesia* / chemically induced
  • Paresthesia* / diagnosis
  • Paresthesia* / epidemiology
  • Peripheral Nervous System Diseases* / chemically induced
  • Peripheral Nervous System Diseases* / diagnosis
  • Peripheral Nervous System Diseases* / epidemiology
  • Prevalence
  • Raynaud Disease* / chemically induced
  • Raynaud Disease* / diagnosis
  • Raynaud Disease* / epidemiology

Substances

  • Antineoplastic Agents
  • Cisplatin

Supplementary concepts

  • Ovarian Germ Cell Cancer