Pneumothorax as a complication of combination antiangiogenic therapy in children and young adults with refractory/recurrent solid tumors

J Pediatr Surg. 2015 Sep;50(9):1484-9. doi: 10.1016/j.jpedsurg.2015.01.005. Epub 2015 Jan 16.

Abstract

Purpose: Antiangiogenic agents show significant antitumor activity against various tumor types. In a study evaluating the combination of sorafenib, bevacizumab, and low-dose cyclophosphamide in children with solid tumors, an unexpectedly high incidence of pneumothorax was observed. We evaluated patient characteristics and risk factors for the development of pneumothorax in patients receiving this therapy.

Patients and methods: Demographics, clinical course, and radiographic data of 44 patients treated with sorafenib, bevacizumab and cyclophosphamide were reviewed. Risk factors associated with the development of pneumothorax were analyzed.

Results: Pneumothorax likely related to study therapy developed in 11 of 44 (25%) patients of whom 33 had pulmonary abnormalities. Median age of patients was 14.7 years (range, 1.08-24.5). Histologies associated with pneumothorax included rhabdoid tumor, synovial sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, and renal cell carcinoma. Cavitation of pulmonary nodules in response to therapy was associated with pneumothorax development (P<0.001). Median time from start of therapy to development of pneumothorax was 5.7 weeks (range, 2.4-31).

Conclusion: The development of cavitary pulmonary nodules in response to therapy is a risk factor for pneumothorax. As pneumothorax is a potentially life-threatening complication of antiangiogenic therapy in children with solid tumors, its risk needs to be evaluated when considering this therapy.

Keywords: Antiangiogenic; Cavitary pulmonary lesions; Pneumothorax; Solid tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Angiogenesis Inhibitors / adverse effects*
  • Angiogenesis Inhibitors / therapeutic use
  • Bevacizumab / adverse effects
  • Bevacizumab / therapeutic use
  • Bone Neoplasms / drug therapy*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Male
  • Neoplasm Recurrence, Local / drug therapy
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives
  • Niacinamide / therapeutic use
  • Osteosarcoma / drug therapy
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / therapeutic use
  • Pneumothorax / chemically induced*
  • Pneumothorax / diagnosis
  • Sarcoma, Ewing / drug therapy*
  • Sarcoma, Synovial / drug therapy*
  • Sorafenib
  • Wilms Tumor / drug therapy*
  • Young Adult

Substances

  • Angiogenesis Inhibitors
  • Phenylurea Compounds
  • Niacinamide
  • Bevacizumab
  • Sorafenib