Presurgical axitinib therapy increases fibrotic reactions within tumor thrombus in renal cell carcinoma with thrombus extending to the inferior vena cava

Int J Clin Oncol. 2018 Feb;23(1):134-141. doi: 10.1007/s10147-017-1169-z. Epub 2017 Jul 27.

Abstract

Background: Clinical benefits of presurgical axitinib therapy for renal cell carcinoma (RCC) extending into the inferior vena cava (IVC) remain unclear. We aimed to investigate surgical benefits and pathological antitumor effects of presurgical axitinib therapy for RCC with IVC thrombus.

Methods: Of 56 consecutive RCC patients with IVC thrombus between January 1994 and December 2016, 41 patients who underwent radical nephrectomy (RN) were categorized as upfront RN (Upfront group) or presurgical axitinib followed by RN (Presurgical group). We retrospectively evaluated safety, radiologic tumor responses, and Ki-67 proliferation index before and after axitinib administration in the Presurgical group. Surgical outcomes, postoperative complications, and fibrosis within the IVC thrombus were compared between the Upfront and Presurgical groups.

Results: The number of patients in the Upfront and Presurgical groups was 31 and 10, respectively. Major presurgical axitinib-related adverse events were grade 2 or 3 hypertension (50%). The median radiological tumor response in the renal tumor, IVC thrombus length, and IVC thrombus volume were -19%, -21 mm, and -54%, respectively. The fibrosis within the IVC thrombus was significantly higher in the Presurgical group (10%) than in the Upfront group (3.4%). The Ki-67 proliferation index was significantly decreased in RN specimens (7.3%) versus needle biopsy specimens (23%) in the Presurgical group. Blood loss and operative duration were significantly lower and shorter, respectively, in the Presurgical group than in the Upfront group.

Conclusions: Presurgical axitinib therapy enhanced tumor reduction accompanied by fibrosis and may contribute to surgical risk reduction for selected patients.

Keywords: Axitinib; Fibrosis; Presurgical therapy; Radiological response; Renal cell carcinoma.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Axitinib
  • Blood Loss, Surgical
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / surgery*
  • Female
  • Fibrosis / pathology
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use*
  • Indazoles / adverse effects
  • Indazoles / therapeutic use*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / surgery*
  • Male
  • Middle Aged
  • Nephrectomy / adverse effects
  • Nephrectomy / methods
  • Postoperative Complications / etiology
  • Preoperative Care
  • Retrospective Studies
  • Thrombosis / diagnostic imaging
  • Thrombosis / drug therapy
  • Thrombosis / pathology
  • Vena Cava, Inferior / pathology
  • Venous Thrombosis / diagnostic imaging
  • Venous Thrombosis / drug therapy
  • Venous Thrombosis / etiology

Substances

  • Imidazoles
  • Indazoles
  • Axitinib