Pazopanib induced a partial response in a patient with metastatic fibrosarcomatous dermatofibrosarcoma protuberans without genetic translocations resistant to mesna, doxorubicin, ifosfamide and dacarbazine chemotherapy and gemcitabine–docetaxel chemotherapy

Abstract

Dear Editor, Fibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP) is a variant of DFSP with increased risk of recurrence and metastasis (~30% and 15%, respectively).1 There are only limited choices of treatment once metastasis occurs. Metastatic DFSP is resistant to conventional chemotherapy. 2Imatinib is effective for metastatic DFSP with genetic translocations involving the platelet-derived growth factor (PDGF) locus. However, it is known that imatinib is not efficacious without the fusion genes, and in such cases there has been almost no promising systemic treatment. We first describe a case of metastatic FS-DFSP without genetic translocations which was resistant to conventional chemotherapy but was sensitive to pazopanib.A 47-year-old man was referred to our department with an abdominal mass (Fig. 1a). Wide local excision was performed. Histopathology revealed that spindle cells were arranged in irregular interwoven fascicles in most parts, while in some parts these cells were lined in diagonal fascicles (Fig. 1b). The tumor cells forming a storiform pattern stained positively for

S1 guidelines for dermatofibrosarcoma protuberans (DFSP) – update 2018

“…There have also been some cases in which a treatment response to other kinase inhibitors, e.g. pazopanib, was achieved after imatinib had become ineffective . In cases of secondary resistance to imatinib, second‐line treatment with another PDGF‐R inhibitor may therefore be useful and has a good chance of success.…”

Cutaneous sarcomas

“…Given the good response rates, especially in a neoadjuvant setting, imatinib is given preference over radiation therapy in English‐speaking countries. In case of primary or secondary imatinib resistance, some case reports have described the use of another multikinase inhibitor: pazopanib; This agent is characterized by a high affinity for the vascular endothelial growth factor receptor (VEGFR) and lower affinities for platelet‐derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and c‐kit . Clinical trial data on its efficacy in larger patient groups is still pending.…”

“…Bei guten Ansprechraten, vor allem im neoadjuvanten Bereich, wird der Therapie mit Imatinib im angloamerikanischen Sprachraum der Vorzug vor einer Radiatio gegeben. Bei primären oder sekundären Resistenzen gegen Imatinib kommt in Fallberichten mit Pazopanib ein weiterer Multikinaseinhibitor zum Einsatz, der eine hohe Affi nität zu vascular endothelial growth factor receptor (VEGFR) und niedrigere Affi nitäten zu platelet derived growth factor receptor (PDGFR), fi broblast growth factor receptor (FGFR) und c-Kit aufweist [ 8 ] . Daten aus klinischen Studien zur breiten Wirksamkeit stehen noch aus.…”

S1‐Leitlinie Dermatofibrosarcoma protuberans (DFSP) – Update 2018

“…Eine klinische Studie an 30 Patienten mit fortgeschrittenen oder metastasierten DFSP und Krankheitsprogress unter einer zunächst wirksamen Erstlinientherapie mit Imatinib zeigte eine Ansprechrate von 40 % unter dem Multikinaseinhibitor Sunitinib . Ein Therapieansprechen nach Versagen von Imatinib ist in Einzelfällen auch für andere Kinaseinhibitoren wie beispielsweise Pazopanib beschrieben . Somit ist bei sekundärer Resistenz gegen Imatinib eine Zweitlinientherapie mit einem anderen PDGF‐R‐Inhibitor sinnvoll und zeigt gute Erfolgsaussichten.…”