Adverse event profile and dose modification of everolimus for advanced renal cell carcinoma in real-world Japanese clinical practice

Jpn J Clin Oncol. 2013 Nov;43(11):1132-8. doi: 10.1093/jjco/hyt121. Epub 2013 Sep 1.

Abstract

Objective: The aim of the study was to assess the safety and efficacy of everolimus therapy for advanced renal cell carcinoma in Japanese patients receiving real-world care.

Methods: Patients who had been treated with everolimus for advanced renal cell carcinoma at 39 Japanese medical centers between January 2010 and November 2011 were retrospectively investigated to assess adverse events and the time to treatment failure.

Results: A total of 180 patients were identified. Their median age was 65 years (range 23-93). The median time to treatment failure was 2.9 months (95% confidence interval 2.4-3.4). The median time to treatment failure was significantly longer in patients with dose modification (4.2 months; 95% confidence interval 3.4-5.0) than in patients without dose modification (1.7 months; 95% confidence interval 1.0-2.3; P < 0.01) after experiencing adverse events. Stomatitis (44%) was the most frequent adverse event, followed by thrombocytopenia (31%), anemia (22%), interstitial pneumonia (22%) and hyperglycemia (17%). Interstitial pneumonia was the most frequent cause of discontinuation in patients who discontinued everolimus due to intolerability regardless of the dose modification status. None of the patients with dose modification of everolimus discontinued everolimus due to thrombocytopenia or leukopenia.

Conclusions: The adverse event profile of everolimus may differ between Japanese and Caucasian patients. Dose modification of everolimus might be associated with longer treatment duration in patients with advanced renal cell carcinoma. Further studies are required to clarify this association. Interstitial pneumonia may be difficult to overcome by dose modification.

Keywords: adverse event; dose modification; dose reduction; everolimus; renal cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / secondary
  • Drug Administration Schedule
  • Everolimus
  • Female
  • Humans
  • Hyperglycemia / chemically induced
  • Japan
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Lung Diseases, Interstitial / chemically induced
  • Male
  • Middle Aged
  • Retrospective Studies
  • Sirolimus / administration & dosage
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives*
  • Stomatitis / chemically induced
  • Thrombocytopenia / chemically induced
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Everolimus
  • Sirolimus