Resolution of Cullen’s sign in patient with metastatic melanoma responding to hypoxia-activated prodrug TH-302

Cullen’s sign, ecchymosis of the subcutaneous periumbilical tissue often described in association with non-malignant conditions such as ruptured ectopic pregnancy or acute pancreatitis, has been reported in malignancies involving the abdomen. In melanoma, hematoma-like metastasis has been observed and can resolve with an effective therapy. We observed resolution of Cullen’s sign (probably hematoma-like metastasis) in a patient with metastatic melanoma. The patient was participating in a phase I clinical trial and treated with TH-302, a hypoxia-activated prodrug. After 2 months on study, complete resolution of Cullen’s sign resolved in concert with extracranial response in lung, liver, and lymph node metastases. Based on the dramatic extracranial response to this investigational agent, additional patients with metastatic melanoma without evidence of brain metastasis were treated on study with TH-302.