Clinical efficacy of preoperative chemotherapy with or without ifosfamide in patients with osteosarcoma of the extremity: meta-analysis of randomized controlled trials

Abstract

Ifosfamide has been used in neoadjuvant chemotherapy since the mid-1980s. Although several studies have been conducted, the results remain controversial. Randomized controlled trials have an improved balance of confounding factors and reliable results. Thus, we performed a meta-analysis based on randomized controlled trials to gather more evidence of the effect of ifosfamide on neoadjuvant chemotherapy for patients with osteosarcoma of the extremity. An electronic search was conducted via the Internet retrieval system to identify eligible trials until September 2014. Odds ratios (ORs) and 95 % confidence interval (CI) were calculated to compare the results of ifosfamide and ifosfamide-free therapies. Four trials with a total of 1,378 patients were eligible for our meta-analysis. Overall, compared with neoadjuvant chemotherapy without ifosfamide, the use of ifosfamide had no advantage in terms of histological response to chemotherapy (cHR; OR 1.36; 95 % CI 0.90-2.03, P = 0.140), 5-year event-free survival (EFS; OR 1.16; 95 % CI 0.789-1.75, P = 0.464), and 5-year overall survival (OS; OR 1.06; 95 % CI 0.70-1.59, P = 0.794). However, improvement was noted in the rate of limb salvage (OR 4.06; 95 % CI 2.04-8.10, P < 0.001). Neoadjuvant chemotherapy with ifosfamide for patients with extremity osteosarcoma might not increase the cHR and exhibited no significant effect on either EFS or OS. However, ifosfamide therapy could significantly increase the rate of limb salvage for osteosarcoma of the extremity, which suggests that the preoperative use of ifosfamide could increase the success rate of limb salvage operation.

Efficacy Comparison of Six Chemotherapeutic Combinations for Osteosarcoma and Ewing's Sarcoma Treatment: A Network Meta‐Analysis

“…According to the results of this network analysis, chemotherapy improves the life-span of patients, and the multiple drugs integrated with IFO and etoposide showed optimal performance, with the lowest HR value when compared with placebo, and most of the treatment options presented a significant difference, which was also confirmed by its highest SUCRA values for all six indices. This conclusion agreed with the outcome of one previous meta-analysis, but stands in conflict with another at the same time, the reason for which might be the confinement of the latter analysis to preoperative chemotherapy and osteosarcoma of the extremities, having examining their overlapping randomized control trials [Fan et al, 2015;Su et al, 2015]. Furthermore, although there was lack of significant difference, the highest SUCRA value found in multiple drugs with IFO alone illustrated its efficiency in reducing the incidence of relapse and lung-metastasis.…”

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

“…This approach has remained relatively unaltered for many years. The inclusion of additional chemotherapeutics including ifosfamide has met with mixed results and meta-analyses have provided conflicting evidence as to whether this provides a clear benefit in all cases [ 51 , 52 ]. Whilst a large number of protocol modifications and experimental therapies have been reported, these at present do not offer credible therapeutic alternatives to improve outcome in affected individuals [ 49 ].…”

Progress in the chemotherapeutic treatment of osteosarcoma (Review)

“…Current chemotherapy programs for OS have included the T protocols developed by Rosen (23) the Cooperative Osteosarcoma Study group protocol of the Germany and Austria OS Chemotherapy Collaborative Research Group and the treatment and investigation of osteosarcoma (TOIS) protocol developed by Jaffe et al (22) at the Rizzoli Institute of Chemotherapy in Italy. MTX, DDP, ADM and IFO are the four primary drugs used for OS chemotherapy (30). For almost 20 years, high-dose and multi-drug neoadjuvant chemotherapy has been the gold standard for OS treatment.…”