Treatment of patients with relapsed and/or cisplatin‐refractory metastatic germ cell tumours: an update

Abstract

Since the introduction of cisplatin-based therapy in the late 1970s, germ cell tumours (GCT) have been one of the successes in oncology with high cure rates even in patients presenting with metastatic disease. For patients with relapse after cisplatin-based therapy, treatment is still curative in approximately 50% of the cases. Management options for these patients include surgery, radiotherapy and use of conventional dose or high-dose chemotherapy (HDCT). Therefore, treatment of relapsed or refractory patients is complex and there is no uniformly accepted approach available. Data comparing conventional dose and HDCT in the first salvage therapy is limited to one randomized trial which was not able to ultimately define optimal treatment. More recently, a large retrospective analysis of nearly 1600 patients not only identified prognostic factors in relapse, but retrospectively suggested a 10-15% benefit regarding overall survival for patients receiving HDCT plus autologous stem cell transplantation over patients receiving conventional-dose chemotherapy. Prognosis in multiply relapsed and primary cisplatin-refractory patients is generally poor. Currently, a number of mechanisms of cisplatin resistance and potential drug targets like global methylation and BRAF mutation status are under investigation in refractory GCT.

miR-223-3p regulates cell growth and apoptosis via FBXW7 suggesting an oncogenic role in human testicular germ cell tumors

“…The vast majority of TGCTs have an excellent cure rate with cisplatin-based treatment. Nevertheless, a subset of patients develops cisplatin resistance resulting in tumor progression and reduced survival (4). Therefore, a better understanding of the molecular mechanisms of TGCT tumorigenesis is needed for identification of new therapeutic targets and treatment development.…”

Three primary testicular tumours: Trials and tribulations of testicular preservation

“…Delayed recurrences are more likely cisplatin-resistant and are preferentially managed with primary resection, making this a crucial distinction. 15 In this patient, each recurrence in the retroperitoneum was assumed to be a new primary, rather than a late recurrence because of the temporal relationship to the respective recurrent primary in the testis, the rarity of late recurrences, and the absence of elevated tumour markers, which would be expected with a late recurrence. The second recurrence was associated with an elevated LDH, but this was consistent with metastatic seminoma.…”

A Rare Case of Embryonal Carcinoma in a Patient with Turner Syndrome without Y Chromosomal Material but Mutations in <b><i>KIT</i></b>, <b><i>AKT1</i></b>, and <b><i>ZNF358</i></b> Demonstrated Using Exome Sequencing

“…And by the initiation of the second-line chemotherapy, disease was also considered cisplatin resistant. This is related to 5-year survival rates of 5-10% in the usage of a 2-drug treatment strategy, with the combination of gemcitabine and paclitaxel as a well-established choice [Koychev et al, 2011]. Research is ongoing in order to better understand the phenomenon of resistance, as well as assessing new targets and thus new treatments to overcome it, and thereby improving chances of cure in patients harboring resistance [Jacobsen and Honecker, 2015].…”