Frailty is a determinant of suboptimal chemotherapy in women with advanced ovarian cancer

Gynecol Oncol. 2020 Sep;158(3):646-652. doi: 10.1016/j.ygyno.2020.05.046. Epub 2020 Jun 6.

Abstract

Objective: To evaluate the relationship between frailty and chemotherapy delivery among women with epithelial ovarian cancer (EOC).

Methods: We included women who underwent primary debulking surgery (PDS) for stage IIIC/IV EOC between 1/2/2003 and 12/30/2011, received adjuvant chemotherapy at our institution, and had data available to calculate a frailty deficit index. Frailty was defined as a frailty deficit index ≥0.15. Relative dose intensity (RDI) of chemotherapy was calculated as the percentage of the standard dose that was administered, and compared between frail and non-frail using the Wilcoxon rank-sum test.

Results: Failure to receive chemotherapy following PDS was twice as common among frail vs. non-frail women (26.7% vs 14.2%, p = 0.001). Of the 169 women who received chemotherapy at our institution, 17.2% (29/169) were frail. Frail women were older (mean, 67.9 vs 62.3 years, p = 0.01), had higher BMI (mean, 29.6 vs 25.7 kg/m2, p = 0.003), and were less likely to complete 6 cycles of chemotherapy (75.9 vs. 93.6%, p = 0.008). Using an RDI cutoff of 85%, frail women were less likely to have adequate doses of carboplatin (15.8 vs. 66.2%, p < 0.001) and paclitaxel (57.9 vs. 80.5%, p = 0.07) despite no differences in dose delays (34.5 vs. 42.1%), dose reductions (65.5 vs. 68.6%), and severe neutropenia (44.8 vs. 39.3%). After adjusting for age, frailty was associated with shorter progression-free (HR 1.58, 95% CI: 0.99-2.50) and overall survival (HR 2.14, 95% CI: 1.35-3.41).

Conclusion: Frail women with EOC were less likely to receive chemotherapy or the optimal dose of chemotherapy after PDS despite no evidence of treatment-related toxicity. Frail EOC patients demonstrated shorter progression-free and overall survival. Further studies are needed to explore the association between frailty, chemotherapy, and survival.

Keywords: Chemotherapy; Frailty; Frailty index; Ovarian cancer; Relative dose intensity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / pathology
  • Carcinoma, Ovarian Epithelial / surgery
  • Cohort Studies
  • Female
  • Frailty / physiopathology*
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / surgery
  • Progression-Free Survival
  • Retrospective Studies

Substances

  • Antineoplastic Agents