Soft tissue sarcoma (STS) are a heterogeneous group of neoplasms arising in mesenchymal tissue Advanced or metastatic disease is commonly observed in patients with STS, and the prognosis of these patients remains poor, with a median overall survival (OS) of 14–17 months。Doxorubicin (brand name: Adriamycin; ADM) is frequently used for the treatment of advanced or metastatic STS; however, the efficacy of ADM alone remains unsatisfactory. Compared with ADM alone, the combination of ADM and ifosfamide (IFO) as the first-line treatment can significantly improve progression-free survival (PFS; 7.4 vs. 4.6 months). However, the combination treatment does not significantly improve OS. Furthermore, increased occurrence of toxicities (grades 3–4) caused by the combination therapy could affect its efficacy and limit its clinical use. Therefore, it is important to reduce the toxicity of this regimen to improve its efficacy.

On Oct 14th 2022, Prof. Zhiguo Luo and his colleagues from Fudan University Shanghai Cancer Center published an article titled “Pegylated liposomal doxorubicin combined with ifosfamide for treating advanced or metastatic soft tissue sarcoma: a prospective, single-arm phase II study” on Clinical Cancer Research.
Pegylated liposomal doxorubicin (PLD) is a liposomal formulation of ADM that demonstrates reduced uptake by the reticuloendothelial system and has an extended circulation time and enhanced concentration in the tumor. These features may make PLD more advantageous than conventional ADM in terms of safety issues, especially cardiotoxicity. Previous studies have indicated favorable activity and toxicity profile for PLD combined withIFO in patients with advanced or metastatic STS. Thus, Prof. Zhiguo Luo and his colleagues performed this prospective, single-arm phase II clinical trial to further evaluate the efficacy and safety of the combination of PLD and IFO in de novo patients with advanced or metastatic STS.
Overall,69 patients with chemotherapy-naive advanced or metastatic STS were enrolled between May 2015 and November 2019. At a median follow-up of 47.2 months, the median PFS and overall survival (OS) were found to be 7.3 (95% CI: 5.7–8.9) and 20.6 (95% CI: 16.3–25.0) months, respectively. The response and disease control rates were 26.1% and 81.2%, respectively. Adverse events were manageable, and no grade 3–4 cardiotoxicities were observed. There was no significant change in left ventricular ejection fraction values between baseline and after treatment (p = 0.669). Exploratory biomarker analysis suggested NF1 single-nucleotide variant was associated with poor OS (p < 0.0001) and PFS (p = 0.044). Additionally, two patients with BRCA2 loss progressed in the initial 2 months and died within 10 months. Improved OS was observed in homologous recombination deficiency (HRD)-negative patients compared with their HRD-positive counterparts (p=0.0056).
To the best of our knowledge, the present study is the first prospective phase II clinical trial of PLD and IFO for the treatment of patients with chemotherapy-naive advanced or metastatic STS. In this study, we found that PLD-IFO demonstrated similar efficacy and lower toxicity compared with that previously reported with ADM-IFO; thus, PLD-IFO represents an effective and well-tolerated treatment option for patients with advanced STS. Further investigation is warranted to assess patient selection, continued use of PLD in responding patients, and comparison between PLD-IFO and ADM-IFO treatments.