Pneumothorax as adverse event in patients with lung metastases of soft tissue sarcoma treated with pazopanib: a single reference centre case series

Abstract

Background: Recently, the phase III PALETTE study introduced pazopanib (Votrient®) as treatment for adult patients with locally advanced or metastatic non-liposarcoma soft tissue sarcoma after prior treatment with doxorubicin and/or ifosfamide. Pneumothorax was reported as adverse event in 8 of 246 treated patients (3.3%) in that study. This case series presents the incidence and clinic of this complication in the Leiden University Medical Centre.

Cases: Forty-three patients were treated with pazopanib of which six patients (14.0%) developed a pneumothorax. These six patients were treated for malignant peripheral nerve sheath tumour, angiosarcoma, synovial sarcoma, fibromyxomatoid sarcoma, pleomorphic sarcoma and endometrial stromal sarcoma. All six patients had subpleural pulmonary or pleural metastases at the start of pazopanib and the pneumothorax developed during or shortly after treatment with pazopanib and was difficult to treat.

Discussion: The incidence reported by us is higher than the incidence in the PALETTE study. Trials with pazopanib in renal cell carcinoma, urothelial carcinoma and cervix carcinoma did not report pneumothorax as an adverse event, suggesting pneumothorax as a specific adverse event in soft tissue sarcoma patients treated with pazopanib. This may be related to the fact that there is often pleural metastatic involvement and cystic degeneration due to pazopanib treatment may add to the risk.

Conclusion: The risk of an, often difficult to treat, pneumothorax during pazopanib therapy should be discussed with the patient before initiation of treatment for a pulmonary metastasized sarcoma and physicians should be alert to the occurrence of such an event.

Keywords: Adverse event; Pazopanib; Pleural metastases; Pneumothorax; Pulmonary metastases; Soft tissue sarcoma.

Figure 1

CT scans of patient 1. A and B: CT scan of the thorax at start of pazopanib, showing a pleural metastasis of the left lung with central hypodensities suggesting necrosis (A, arrow) and showing a pulmonary metastasis in the right lung (B, arrow). C and D: CT scan, when presenting with a left-sided pneumothorax (D), showing progressive hypodensity of the pleural metastasis on the left side (C, arrow) and central cavitation in the metastasis in the right lung (D, arrow).

Figure 2

CT scans and X-thorax of patient 2. A: CT scan at start of pazopanib showing metastases in both lungs with a large necrotizing metastasis on the left side. The pleural metastasis indicated by the arrow is also visible in B, which is a CT scan after 3 months of pazopanib treatment, now showing cavitations. C is also an image from the CT scan after 3 months of pazopanib treatment showing a metastasis (arrow) with cavitation next to the pleura. D: The X-thorax shows the right sided pneumothorax. The visceral pleural line is indicated by the arrow.

Figure 3

CT scans of patient 3. Routine follow-up CT scan showing the pneumothorax on the right side. A shows one of the pulmonary metastasis, B shows a pleural metastasis.

Figure 4

CT scan of patient 4. The CT scan shows the massive pulmonary metastases and a left-sided pneumothorax.

Figure 5

CT scans of patient 5. A: CT scan before the start of pazopanib showing multiple metastases in the right lung, one is indicated by the arrow. B: Routine follow-up CT scan during pazopanib treatment showing the left-sided pneumothorax and the earlier mentioned metastasis in the right lung is now showing cavitation.

Figure 6

CT scan of patient 6. A: CT scan at start of pazopanib showing a metastasis in the right lower lobe with a diameter of 49.6 mm. B: CT scan after 12 weeks of pazopanib (6 weeks of treatment and 6 weeks on hold due to liver toxicity), showing a decrease in diameter of the metastasis to 33.1 mm. C: CT scan showing the bilateral pneumothorax.