In vitro drug sensitivity predicts response and survival after individualized sensitivity-directed chemotherapy in metastatic melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group.

PURPOSE: In vitro sensitivity assays are promising tools to predict the individual outcome of different chemotherapy regimens. However, a direct association between in vitro and in vivo chemosensitivity has to be shown by clinical studies. This multicenter phase II trial was aimed to investigate the efficacy of a sensitivity-directed, first-line chemotherapy in metastasized melanoma patients, and to prove an association between in vitro sensitivity and therapy outcome. PATIENTS AND METHODS: The primary study end point was objective response; secondary end points were safety, overall survival, and progression-free survival. Viable tumor cells obtained from metastatic lesions were tested for chemosensitivity to seven single drugs and five drug combinations using an ATP-based luminescence viability assay. RESULTS: Out of 82 recruited patients (intention-to-treat), 57 received assay-directed chemotherapy and 53 were evaluable for all study end points (per protocol). The drug combinations used were gemcitabine+treosulfan, paclitaxel+cisplatin, paclitaxel+doxorubicin, and gemcitabine+cisplatin. The per protocol population could be divided into 22 (42%) chemosensitive and 31 (58%) chemoresistant patients by an arbitrary chemosensitivity index. Objective response was 36.4% in chemosensitive patients compared with 16.1% in chemoresistant patients (P=0.114); progression arrest (complete response+partial response+stable disease) was 59.1% versus 22.6% (P=0.01). Chemosensitive patients showed an increased overall survival of 14.6 months compared with 7.4 months in chemoresistant patients (P=0.041). CONCLUSION: In vitro chemosensitivity testing may be worthy of further exploration to see if it could be a useful tool to predict the outcome of melanoma patients treated with a sensitivity-directed chemotherapy. Therefore, these preliminary results will be evaluated by a planned phase III trial using a randomized, standard-regimen controlled setting.

Jo-1 positive paraneoplastic systemic sclerosis in a patient with metastatic melanoma.

A link between systemic sclerosis (SSc) and malignancy is suggested by epidemiological evidence, but the underlying mechanism connecting both diseases has been a source of ongoing controversy. Here, we describe the first case of paraneoplastic SSc secondary to a primarily diagnosed melanoma. Two months after diagnosis of metastatic melanoma, a 40-year-old female presented with high serum titers of antinuclear antibodies (ANA), but no symptoms of autoimmune disease. Five months later, the onset of Raynaud's phenomenon together with highly positive Jo-1 antibodies was observed. The following clinical course of scleroderma was correlated to melanoma remission and progression. Finally, the patient developed severe pulmonary fibrosis, massive pleural effusion, severe thoracic scleroderma and necrosis of the fingertips, simultaneously with a progression of melanoma to disseminated lymph node metastases and a small brain metastasis. This rare case of SSc concurrent with melanoma suggests that besides other possible mechanisms, paraneoplastic etiology can be responsible for the association between SSc and cancer.