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 sensitivitydirected chemotherapy. Therefore, these preliminary results will be evaluated by a planned phase III trial using a randomized, standard-regimen controlled setting.Melanoma is a cutaneous neoplasm known for its high aggressiveness, its early dissemination of metastases, and its poor prognosis once metastasized. Chemotherapy with dacarbacine (DTIC) does actually apply as the standard treatment regimen in metastasized melanoma, with reported response rates of only 10% to 18% (1). Even these might be overestimated, as recent studies using new standardized evaluation criteria (2) revealed much lower response rates of 6% to 7% (3, 4). This poor outcome does not rely on an impaired penetration of chemotherapeutics into the tumor, but has been proposed to be caused by chemoresistance mechanisms intrinsic to melanoma cells (5, 6). Moreover, biochemotherapy and immunotherapy regimens did not prove to be superior to DTIC (1, 7).Due to this unfavorable situation, a number of nonstandard chemotherapeutics were tested in small pilot studies to prove a stronger efficacy in melanoma. Although complete remissions of metastatic lesions could only be observed in few patients

In metastatic melanoma treatment with TMZ + IFN-alpha leads to a significantly superior OR rate compared to treatment with TMZ alone, which did not translate into prolonged survival in our study population.