Comprehensive analysis of published studies involving systemic treatment for chondrosarcoma of bone between 2000 and 2013

Abstract

BackgroundThe majority of patients with chondrosarcoma of bone have an excellent overall survival after local therapy. However, in case of unresectable locally advanced or metastatic disease the outcome is poor and limited treatment options exist. Therefore we conducted a survey of clinical phase I or II trials and retrospective studies that described systemic therapy for chondrosarcoma patients.Materials and methodsUsing PubMed, clinicaltrials.gov, the Cochrane controlled trial register and American Society of Clinical Oncology (ASCO) abstracts a literature survey was conducted. From the identified items, data were collected by a systematic analysis. We limited our search to semi-recent studies published between 2000 and 2013 to include modern drugs, imaging techniques and disease evaluations.ResultsA total of 31 studies were found which met the criteria: 9 phase I trials, 11 phase II and 8 retrospective studies. In these studies 855 chondrosarcoma patients were reported. The tested drugs were mostly non-cytotoxic, either alone or in combination with another non-cytotoxic agent or chemotherapy. Currently two phase I trials, one phase IB/II trial and three phase II trials are enrolling chondrosarcoma patients.ConclusionBecause chondrosarcoma of bone is an orphan disease it is difficult to conduct clinical trials. The meagre outcome data for locally advanced or metastatic patients indicate that new treatment options are needed. For the phase I trials it is difficult to draw conclusions because of the low numbers of chondrosarcoma patients enrolled, and at different dose levels. Some phase II trials show promising results which support further research. Retrospective studies are encouraged as they could add to the limited data available. Efforts to increase the number of studies for this orphan disease are urgently needed.

Systemic therapy for selected skull base sarcomas: Chondrosarcoma, chordoma, giant cell tumour and solitary fibrous tumour/hemangiopericytoma

“…anthracyclineand gemcitabine-based combinations, ifosfamide, cisplatin. 6,7 With conventional cytotoxic chemotherapy, RECIST disease stabilisations are more commonly observed than objective responses. In the largest retrospective series, published by Italiano et al, cumulative objective response rate (ORR) was significantly dependant on the histotype, being 11% for conventional chondrosarcoma, with a median progression-free survival (PFS) of 5 months.…”

“…7 Probably, molecular heterogeneity and different pathogenetic mechanisms within different chondrosarcoma variants complicate this issue. 11 The initial enthusiasm driven by pre-clinical data with Hedgehog pathway inhibitors has been frustrated after results of a Phase 2 study in which no objective responses were observed.…”

Study protocol of a phase IB/II clinical trial of metformin and chloroquine in patients withIDH1-mutated orIDH2-mutated solid tumours

“…The current standard therapy for chondrosarcoma is surgery. There is no evidence for a benefit of (adjuvant) radiotherapy or chemotherapy, as chondrosarcoma is considered to be highly therapy resistant 7. Consequently, the 1-year survival rate of metastasised high-grade chondrosarcoma is <10% 8.…”

“…There is no evidence for a benefit of (adjuvant) radiotherapy or chemotherapy, as chondrosarcoma is considered to be highly therapy resistant. 7 Consequently, the 1-year survival rate of metastasised high-grade chondrosarcoma is <10%. 8 Gliomas vary from WHO grade II diffuse astrocytoma and diffuse oligodendroglioma, with median survivals of more than 5 years, 9 to WHO grade IV glioblastoma, with a median survival of only 15 months despite aggressive treatment using radiotherapy and temozolomide.…”

Molecular oncogenesis of chondrosarcoma: impact for targeted treatment

“…Surgery is the cornerstone of the primary management of chondrosarcoma. The current treatment options for patients with unresectable or metastasized disease are limited as chondrosarcomas are relatively chemotherapy-resistant and radiotherapy-resistant [9,10]. The outcome of unresectable conventional chondrosarcoma is 48% at 1 year and 2% at 5 years [11 & ].…”