Chemosensitivity-directed therapy compared to dacarbazine in chemo-naive advanced metastatic melanoma: A multicenter randomized phase-3 DeCOG trial

Selma Ugurel*, Carmen Loquai, Patrick Terheyden, Dirk Schadendorf, Erika Richtig, Jochen Utikal, Ralf Gutzmer, Knuth Rass, Cord Sunderkötter, Annette Stein, Michael Fluck, Martin Kaatz, Uwe Trefzer, Katharina Kähler, Rudolf Stadler, Carola Berking, Christoph Höller, Laura Kerschke, Lutz Edler, Annette Kopp-SchneiderJürgen C. Becker

*Corresponding author for this work
1 Citation (Scopus)


Chemotherapy still plays an important role in metastatic melanoma, particularly for patients who are not suitable or have no access to highly efficacious new therapies. Pre-therapeutic chemosensitivity testing might be useful to identify optimal chemotherapy regimens for individual patients. This multicenter randomized phase-3 trial was aimed to test for superiority of chemosensitivity-directed combination chemotherapy compared to standard dacarbazine monochemotherapy, and to demonstrate the chemosensitivity test result as prognostic in metastatic melanoma. Chemo-naive patients with advanced melanoma were biopsied from metastatic lesions. Tumor cells were isolated and tested ex-vivo for sensitivity to chemotherapeutic agents using an ATP-based viability assay. Patients with evaluable test results were randomly assigned to receive either chemosensitivity-directed combination chemotherapy (paclitaxel+cisplatin, treosulfan+gemcitabine, treosulfan+cytarabine), or dacarbazine. The primary study endpoint was overall survival (OS). After inclusion of 287 patients and a median follow-up of 26 months, the per-protocol population (n=244) showed no difference in OS between chemosensitivity-directed therapy and dacarbazine (median 9.2 vs 9.0 months, HR=1.08, p=0.64). The disease control rate (CR+PR+SD) tended to be higher in patients treated with chemosensitivity-directed therapy (32.8% vs 23.0%, p=0.088); objective response rates (CR+PR) showed no difference between groups (10.7% vs 12.3%, p=0.90). Patients whose tumors were tested chemosensitive showed no better OS or response rate than patients with chemoresistant tumors. Severe toxicities (CTC grade 3-4) were significantly more frequently observed with chemosensitivity-directed combination chemotherapy than with dacarbazine (40.2% vs 12.3%, p < 0.0001). These results indicate, that chemosensitivity-directed combination chemotherapy is not superior to dacarbazine, but leads to significantly more severe toxicities.

Original languageEnglish
Issue number44
Pages (from-to)76029-76043
Number of pages15
Publication statusPublished - 01.01.2017

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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