Using Single-Agent Therapy in Adult Patients with Advanced Soft Tissue Sarcoma Can Still Be Considered Standard Care

Abstract

Learning ObjectivesAfter completing this course, the reader will be able to:1. Discuss the current status of the chemotherapeutic treatment of advanced soft tissue sarcomas in adult patients.2. Explain the pitfalls in trial design when reading published papers on performed clinical studies.3. Discuss the importance of identifying the several subtypes comprising the group of soft tissue sarcomas. AbstractThe group of soft tissue sarcomas in adult patients is a heterogeneous group with more than 40 different subtypes. While local treatment remains the mainstay for localized disease, systemic chemotherapy can importantly contribute in the treatment of advanced soft tissue sarcoma. For patients with metastatic disease, chemotherapy is a palliative treatment in the vast majority of the cases. In this setting, toxicity should not outweigh the potential benefits resulting from chemotherapy. In patients with locally advanced disease too extensive for local treatment, systemic chemotherapy can contribute to cure, provided that tumor shrinkage renders subsequent optimal local treatment possible. In these cases, chemotherapeutic regimens yielding the highest response rates achievable should be used. In the last decades, several randomized studies have aimed to determine whether combination regimens yield benefit over single-agent treatment in terms of response rate and overall survival. This review addresses the current available data on chemotherapy for adult patients with soft tissue sarcoma, excluding gastrointestinal stromal tumor, the Ewing-like sarcomas, and other small blue round cell tumors. In addition, it is increasingly recognized that future research in soft tissue sarcoma should focus on the identification of tumor factors that can serve as targets for treatment and that the diverse tumor subtypes should be analyzed separately for their sensitivity to systemic treatment. This review also focuses on these and other strategies that will hopefully lead to better outcomes in this disease entity in the near future. The Oncologist 2005;10:833-841 Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com CME CME This material is protected by U.S.

Trends in survival for patients with metastatic soft‐tissue sarcoma

“…With the exceptions of rhabdomyosarcomas and soft part Ewing sarcomas, systemic chemotherapy for the different STS subtypes is based on doxorubicin and ifosfamide, which remain the cornerstone first-line treatment in 2010. 10,11 In recent years, however, the insight has emerged that systemic therapy should become more tailored, and particularly for STS, according to histologic subtype. This approach is illustrated clearly by the relevant activity of imatinib in advanced dermatofibrosarcoma protuberans, 12,13 paclitaxel in angiosarcoma, 14,15 gemcitabine in leiomyosarcomas, 16,17 trabectedin in patients with myxoid/round cell liposarcomas, 18 and of mammalian target of rapamycin inhibitors in perivascular epithelioid cell tumors.…”

Comparison of Efficacy and Toxicity of First Line Chemotherapy with or without Epirubicin for Patients with Advanced Stage Soft Tissue Sarcoma

“…Palliative chemotherapy is considered the only therapeutic option for patients with advanced STS which not amenable to surgery or radiotherapy (Clark et al, 2005). Doxorubicin remains the best single agent with proven activity, providing a response rate of 15%-35% in metastatic soft tissue sarcoma whatever the histological subtypes (Sleijfer et al, 2005). In EORTC 61012 trial, with 455 locally advanced STS, after a median follow-up of 56 months ,Professor Graaf concluded that doxorubicin/ ifosfamide compared with doxorubicin alone was associated with no significant difference in overall survival (OS) but with a longer PFS (median: 7.4 m versus 4.6 m; HR 0.74; 95% CI: 0.60-0.90, p=0.003) and higher overall DOI:http://dx.doi.org/10.7314/APJCP.2013.14.12…”

“…Systemic chemotherapy given with palliative intent is the only available treatment option for many patients with locally advanced unresectable and metastatic STS, yet the results are generally unsatisfactory, few patients experiencing long-term survival (Mocellin et al, 2006). Doxorubicin, first reported to have activity in sarcomas 40 years ago, remains an important first-line treatment of choice for many subtypes, Single -agent doxorubicin is the most widely accepted treatment option for these tumors (Sleijfer et al, 2005). Advanced and metastatic STSs are currently treated by doxorubicin and / or ifosfamidebased regimens at first line ,with an objective response (OR) of 23% to 48% (Maurel et al, 2009).…”

The Pharmacologic Basis of Ifosfamide Use in Adult Patients with Advanced Soft Tissue Sarcomas

“…A dose-response relationship for doxorubicin has been described, and it is therefore commonly recommended that doxorubicin be administered at doses between 70 mg/m 2 and 80 mg/m 2 in 3-week intervals [7,8]. The use of doxorubicin is mainly limited by myelosuppression and cardiomyopathy.…”