Efficacy and safety of Specific Conjugate Particle (SCP)- Doxorubicin in Patients with Soft Tissue Sarcoma, a Randomized Clinical Study

Objective: Doxorubicin has been the mainstay of treatment foradvanced STS. However, the conventional formulation of doxorubicinhas not been used clinically, due to poor penetration of the naturalphysiologic barriers, poor water solubility and high side effects profile. To overcome these obstacles authors compared the use of Specific conjugate particle doxorubicin (Group 1), a proven efficacious agent with advanced technical drug, and PEGylated liposomal Doxorubicin (Group 2) in a randomized prospective Phase III trial involving patients with advanced soft tissue sarcomas. Methods: We recruited eighty-four patients (32 males and 52 females) with histologically confirmed locally advanced or metastatic Soft Tissue Sarcoma (STS). The participants were between the ages of 18 and 70 years. Patients were randomized to receive either Specific Conjugate Particle Doxorubicin (SCP-Doxorubicin) and paclitaxel or the conventionally accepted PEGylated Liposomal Doxorubicin (PEGDoxorubicin) and paclitaxel. Patients received 45 mg/m2 of either PEG-Doxorubicin or SCP-Doxorubicin by an intravenous infusion over 30 minutes on day 1, followed by paclitaxel 150 mg/m2 as an intravenous infusion over three hours on day 1. We repeated treatment cycles every 28 days. Patients received a total of six cycles unless disease progression or unacceptable toxicity occurred. Results:Patients receiving SCP-Dox had a significantly better response to therapy (more CR, PR and SD) than those receiving PEG-Dox (p<0.05). Out of eighty four patients, 3 complete responses (CRs) and 16 Partial Responses (PRs) were observed. Stable Disease (SD) lasting longer than 16 weeks was noted in 36 patients (yielding an aggregate over all response rates of 65.5%). Patients receiving SCP-Dox had better ORR, PFS, and OS than those receiving PEGDox. Sixteen adverse events occurred in patients receiving PEG-Dox, whereas there were only six adverse events in patients who received SCP-Dox. Neutropenia was the most common adverse event in both the groups (p<0.05). Conclusion: SCP-Dox was found to have superior efficacy to PEG-Dox in the management of soft tissue sarcoma irrespective of the primary disease sites. In addition, SCP-Dox proved to be a comparatively safer treatment regimen, with no major side effects when compared to PEG-Dox.