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

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.

<p>Anorexia, Hypertension, Pneumothorax, and Hypothyroidism: Potential Signs of Improved Clinical Outcome Following Apatinib in Advanced Osteosarcoma</p>

“…1 The pathophysiologic mechanisms of pneumothorax in this setting are not clearly known, but may include fistula formation between the lung parenchyma and pleural space due to necrosis of a subpleural tumor nodule, infarction and necrosis of tumor emboli, over distension, and subsequent rupture of alveoli following VEGFR-TKI therapy. 15,17 In our study, pneumothorax was reported far more frequently than other solid tumors and with appropriate management, the prognosis seemed to be far more better than those that did not have it.…”

“…[32][33][34] Most of the AEs reported with apatinib can be ascribed to VEGFR inhibition and are consistent with the AEs observed with other VEGFR TKIs. 10,15,17,33 As tumor growth addiction to the specific pathway that is effectively targeted may be the link between a mechanism-based toxicity and efficacy, the biological basis of AEs might be pharmacological, with higher drug exposure being associated with greater toxicity and antitumor activity. 10,15 Some TKI-associated AEs correlate with improved patient outcomes.…”

“…10,15 Some TKI-associated AEs correlate with improved patient outcomes. 17,33 An awareness of the mode of action can help the physician anticipate potential drug interactions, and an appreciation of the most common AEs but with appropriate management in case those AEs progressing into grades 3-4. The objectives of this single institution, phase two, open-label, single-arm study were to assess the efficacy and safety of apatinb in patients with heavily pretreated advanced osteosarcoma, and to evaluate the potential of apatinib-induced AEs for efficacy prediction.…”

“…Pneumothorax as a complication of antiangiogenesis therapy in children and young adults with refractory/recurrent solid tumors has been shown to be an indicator of a favorable prognosis. 17 Osteosarcoma tends to have pulmonary metastasis. 1 The pathophysiologic mechanisms of pneumothorax in this setting are not clearly known, but may include fistula formation between the lung parenchyma and pleural space due to necrosis of a subpleural tumor nodule, infarction and necrosis of tumor emboli, over distension, and subsequent rupture of alveoli following VEGFR-TKI therapy.…”

“…Anti-angiogenesis TKIs have some common toxicities such as hypertension, hand-foot skin reactions, hypothyroidism, fatigue, and anorexia. [11][12][13][14] However, previous trials [15][16][17] on other tumors have indicated that some of these toxicities correspond to a favorable outcome with these drugs.…”