The following is a summary of a randomized clinical study that we undertook that yielded very promising results regarding the role of Specific Conjugate Particle (SCP) therapy in the management of advanced Soft Tissue Sarcoma (STS). STSs remain a challenging malignancy to treat, not only because of their high clinicopathological heterogeneity but also because of their limited responsiveness to most conventional chemotherapeutic agents. A patient with STS, even after complete local disease control, often relapse locally or with distant metastases. Almost 50% of patients where there is good local control will eventually present with metastatic disease, and patients with advanced or metastatic STS have a dismal prognosis, with median survival less than one year. Therefore, it is essential that other treatment modalities are developed and evaluated. Given that mandate and the excellent results that we have observed in our other SCP therapy studies, we undertook a prospective Randomized Clinical Trial (RCT).
Entry criteria for the study included that patients must have histologically confirmed advanced STS, and be less than 75 years of age. No prior chemotherapy for advanced disease was allowed. However, previous adjuvant or neo-adjuvant treatment with an anthracycline-containing regimen was permitted provided that there was at least a 12-month treatment-free interval.
Doxorubicin has been the mainstay of treatment for advanced STS and has consistently produced responses as monotherapy in more than 20% of previously untreated patients. Patients were randomized to receive either Specific Conjugate Particle Doxorubicin (SCP-Doxorubicin) and paclitaxel or the conventionally accepted Pegylated Liposomal Doxorubicin (PEG- Doxorubicin) 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. All patients received standard premedication before paclitaxel administration, to prevent hypersensitivity reactions.
We enrolled Eighty-four patients with locally advanced or metastatic STS and in those subjects, we observed three complete responses (CRs) and 16 Partial Responses (PRs). We noted Stable Disease (SD) lasting longer than 16 weeks in 36 patients (yielding an aggregate overall response rate of 65.5%).
We utilized Cox’s Regression Model of life table analysis to assess outcomes, and we confirmed statistical significance via Kaplan-Meier estimates. Patients receiving SCP-Doxorubicin had a significantly better response to therapy (more CR, PR and SD) than those receiving PEG- Doxorubicin (p<0.05). A total of 16 adverse events occurred in patients receiving PEG-Doxorubicin, whereas there were only six adverse events in patients who received SCP Doxorubicin (p<0.05). Neutropenia was the most common adverse event in both the groups.
In conclusion, our study has produced very promising results regarding the role of SCP- Doxorubicinin managing patients who have advanced soft tissue sarcoma. We found SCP-Doxorubicin to have superior efficacy to PEG-Doxorubicin independent of the patient’s prior therapeutic regime and stage of carcinoma. Furthermore, SCP-Doxorubicin was found to be a comparatively safer treatment regimen with no major side effects and a significantly lower adverse event rate than PEG- Doxorubicin. Given these findings, we plan to seek a 505(b)(2) expedited route to regulatory approval so that SCP therapy can be made available for the management of this otherwise poor prognosis group of patients. You can view a PowerPoint presentation of this study by clicking on this link .
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