Systematic Review of Recurrent Osteosarcoma Systemic Therapy

Abstract

Osteosarcoma is the most frequent primary bone cancer, mainly affecting those of young ages. Although surgery combined with cytotoxic chemotherapy has significantly increased the chances of cure, recurrent and refractory disease still impose a tough therapeutic challenge. We performed a systematic literature review of the available clinical evidence, regarding treatment of recurrent and/or refractory osteosarcoma over the last two decades. Among the 72 eligible studies, there were 56 prospective clinical trials, primarily multicentric, single arm, phase I or II and non-randomized. Evaluated treatment strategies included cytotoxic chemotherapy, tyrosine kinase and mTOR inhibitors and other targeted agents, as well as immunotherapy and combinatorial approaches. Unfortunately, most treatments have failed to induce objective responses, albeit some of them may sustain disease control. No driver mutations have been recognized, to serve as effective treatment targets, and predictive biomarkers of potential treatment effectiveness are lacking. Hopefully, ongoing and future clinical and preclinical research will unlock the underlying biologic mechanisms of recurrent and refractory osteosarcoma, expanding the therapeutic choices available to pre-treated osteosarcoma patients.

3′,4′-Dihydroxyflavonol Modulates the Cell Cycle in Cancer Cells: Implication as a Potential Combination Drug in Osteosarcoma

“…OS mainly affects people at young ages, and is the most common primary bone cancer. Although the chances of cure have significantly increased with surgery and cytotoxic chemotherapy, recurrent and refractory disease are still challenging, with limited therapeutic alternatives in current use and poor results [ 5 ]. As combination therapies might produce a stronger treatment for a disease compared to individual treatments, there are currently more than 10,000 clinical trials in progress, only in the United States, regarding the application of combination therapies for several diseases, namely cancer, infectious diseases, autoimmune, cardiovascular, metabolic, and neurological disorders.…”

“…It has an annual incidence rate of approximately 3.1 cases per million in the United States, accounting for less than 1% of all newly diagnosed cancers in adults and 3-5% of those in children. Although rare, it is the most common primary malignancy in adolescents outside leukemia and lymphoma, and the most common primary malignancy of bone Pharmaceuticals 2021, 14, 640 2 of 15 in children [3][4][5][6]. Prior to the advent of chemotherapy, OS was generally a fatal disease although over the last 30 years, no significant improvements were achieved for metastatic OS [7].…”

Bone sarcoma: Success through interdisciplinary collaboration

“…Multiple non-chemotherapeutic drugs have also been tested in phase II trials, most notably tyrosine-kinase inhibitors. 44 , 47 , 48 A major hurdle in the testing of any new osteosarcoma agent – not true for Ewing sarcoma – is that the tumour’s osteoid matrix prevents shrinkage even when the agent in question kills all osteosarcoma cells. Hence, innovative ways to measure a drugs efficaciousness must be sought and found.…”

“… 49 Methods used recently to try to define a drug’s activity include, for example, randomized comparisons of the time to progression. 47 , 48 It remains to be seen if any of the investigated agents will be able to increase cure rates.…”

Circulating Long Non-Coding RNAs as Novel Potential Biomarkers for Osteogenic Sarcoma

“…Nowadays, various clinical practices for OS have been notably implemented, including chemotherapy, radiotherapy, surgery, and targeted therapy; yet, the prognosis for OS still remains poor [5,6]. In fact, approximately 20% of patients showed clinical metastasis at presentation, with a 5-year survival rate less than 30% [7].…”