Which goals should we pursue in each line of treatment for advanced soft tissue sarcoma?

2019 ◽  
Vol 15 (26s) ◽  
pp. 17-23
Author(s):  
Javier Martin-Broto ◽  
Nadia Hindi ◽  
David S Moura
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Disease Stage ◽  
Treatment Goals ◽  
Tumor Shrinkage ◽  
First Line ◽  
Advanced Soft Tissue Sarcoma ◽  
First Line Therapy ◽  
Line Therapy

Treatment goals for advanced soft tissue sarcoma (STS) vary according to disease stage and treatment line. In potentially resectable advanced disease, the goal of treatment is tumor shrinkage to facilitate surgical resection with better margins. Doxorubicin in combination with ifosfamide (or dacarbazine) is first-line therapy of choice in this setting. Tumor shrinkage is relevant not only for surgical rescue but also to obtain rapid symptomatic relief related to tumor volume. Doxorubicin monotherapy can be selected as first-line therapy in cases where disease control with less morbidity is the objective. Second-line therapy for metastatic disease generally aims for disease stabilization with good quality of life although, in some palliative or potentially resectable cases, tumor shrinkage may be relevant. To date, treatment aim has not been a critical factor in the design of clinical trials in advanced STS. In clinical practice, however, treatment is selected according to aim. Future clinical trials in patients with advanced STS should take treatment goals into account. Using illustrative case studies, evidence is examined which supports the current approach to treatment of advanced STS.

scholarly journals Update on Systemic Therapy for Advanced Soft-Tissue Sarcoma

2020 ◽  
Vol 27 (11) ◽  
pp. 25-33 ◽  
Author(s):  
A. Smrke ◽  
Y. Wang ◽  
C. Simmons
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Systemic Therapy ◽  
English Language ◽  
Standard Of Care ◽  
Current Evidence ◽  
First Line ◽  
First Line Therapy

Background: Soft-tissue sarcoma (sts) represents a rare group of mesenchymal neoplasms comprising more than 50 heterogeneous subtypes. Great efforts have been made to increase the understanding of the treatment of advanced sts (unresectable or metastatic disease). We set out to determine whether outcomes for patients with advanced sts have improved over time and to assess the current evidence for systemic therapy. Methods: In a scoping review, we evaluated the contemporary evidence for systemic treatment of advanced sts in adults (>18 years of age). Phase i, ii, and iii studies of systemic therapy for advanced sts published in the English language were included. After abstract and full-text review of seventy-seven studies, sixty-two trials met the inclusion criteria. Results: The number of clinical trials conducted and published in advanced sts has increased over the last 30 years. Although median overall survival has increased, attempts at improving first-line therapy through dose intensification, doublet chemotherapy, or alternative backbones have not been successful. The optimal therapy beyond anthracyclines remains a challenge, especially given the heterogeneity that grouping multiple sts subtypes within clinical trials creates. However, increasing numbers of agents are being studied, and several studies had shown isolated benefit in progression-free or overall survival. Summary: First-line systemic therapy with an anthracycline remains the standard of care for advanced sts. However, choice of subsequent therapy beyond anthracyclines remains challenging. Novel systemic therapies, use of molecular diagnostics to direct therapy, subtype-specific trials, and learnings from real-world retrospective data are all important for improving outcomes in patients with advanced sts.

scholarly journals PML expression in soft tissue sarcoma: Prognostic and predictive value in alkylating agents/antracycline-based first line therapy

2012 ◽  
Vol 227 (4) ◽  
pp. 1657-1662 ◽  
Author(s):  
Bruno Vincenzi ◽  
Daniele Santini ◽  
Gaia Schiavon ◽  
Anna Maria Frezza ◽  
Marianna Silletta ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Predictive Value ◽  
Alkylating Agents ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

scholarly journals Doxorubicin/Adriamycin Monotherapy or Plus Ifosfamide in First-Line Treatment for Advanced Soft Tissue Sarcoma: A Pooled Analysis of Randomized Trials

2021 ◽  
Vol 11 ◽  
Author(s):  
Bi-Cheng Wang ◽  
Bo-Hua Kuang ◽  
Bo-Ya Xiao ◽  
Guo-He Lin
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Randomized Clinical Trials ◽  
Objective Response ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
First Line ◽  
Open Label ◽  
Advanced Soft Tissue Sarcoma

BackgroundDoxorubicin/Adriamycin (ADM) alone or combined with ifosfamide (IFO) (AI) is available for previously untreated advanced soft tissue sarcoma (ASTS). However, the clinical choice between them remains controversial. In this pooled analysis, we comprehensively compared the efficacy and tolerability of AI versus ADM in patients with ASTS.MethodsPubMed, Web of Science, EMBASE, and Cochrane Library were systematically searched from inception to April 14, 2021. Eligible studies were randomized clinical trials comparing AI to ADM. The primary outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Discontinuation rate (DR) and toxic death (TD) were explored as secondary outcomes.ResultsOverall, three open-label randomized phase 2/3 clinical trials with a total of 1108 newly diagnosed ASTS patients were enrolled. Between AI and ADM, pooled hazard ratios were 0.93 (95% confidence interval 0.58-1.50, p = 0.78) for OS and 0.85 (0.57-1.25, p = 0.41) for PFS. While pooled risk ratios for ORR, DR, and TD were 1.37 (0.94-1.99, p = 0.10), 1.04 (0.74-1.46, p = 0.82), and 0.68 (0.19-2.36, p = 0.54) respectively. No publication bias was observed across the studies.ConclusionIn the first-line setting, adding IFO to ADM failed to benefit ASTS patients against ADM alone, even with comparable tolerability.

scholarly journals Eribulin as a first-line treatment for soft tissue sarcoma patients with contraindications for doxorubicin

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kenji Tsuchihashi ◽  
Hitoshi Kusaba ◽  
Tomoyasu Yoshihiro ◽  
Toshifumi Fujiwara ◽  
Nokitaka Setsu ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Adverse Events ◽  
Safety Management ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
First Line Treatment

AbstractDoxorubicin is a first-line therapy for patients with unresectable advanced soft tissue sarcoma (STS). However, because of cardiotoxicities, it is not used for patients with cardiac problems. Eribulin has exhibited efficacy for advanced STS in second- or later-line treatments. In the present study, we retrospectively analyzed the efficacy and safety of first-line eribulin therapy for patients with advanced STS unable to receive doxorubicin. Six of 28 patients who received eribulin as any line treatment received eribulin as a first-line treatment. The reasons for avoiding doxorubicin were as follows: cardiac problems for four patients and advanced age for two. Median progression-free survival (PFS) of the patients who received eribulin as first-line and, second or later-line therapy were 9.7 months (95% CI: 1.0-not reached) and 3.9 months (95% CI: 2.7–5.9), which were not significantly different. The reasons for discontinuation of eribulin were disease progression and adverse events (2 fatigue and 1 neuropathy) for three patients each. No treatment-related cardiotoxicity was observed. The findings of this study indicated that eribulin exhibits meaningful efficacy for the patients with contraindications for doxorubicin as a first-line treatment without cardiac adverse events. However, appropriate safety management is necessary because older patients are typically among those intolerable of doxorubicin.

scholarly journals Update on Systemic Therapy for Advanced Soft Tissue Sarcoma

2020 ◽  
Vol 26 ◽  
Author(s):  
A. Smrke ◽  
Y. Wang ◽  
C. Simmons
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Systemic Therapy ◽  
English Language ◽  
Standard Of Care ◽  
Current Evidence ◽  
First Line ◽  
First Line Therapy ◽  
Full Text Review

Background: Soft tissue sarcoma (STS) is a rare group of mesenchymal neoplasms which contains over 50 heterogenous subtypes.  There have been great efforts to increase the understanding of treatment of advanced STS (unresectable or metastatic disease). We wished to determine if outcomes for patients with advanced STS have improved over time, and to assess the current evidence for systemic therapy. Methods: We performed a scoping review to evaluate the contemporary evidence for systemic treatment of advanced soft tissue in adults (>18 years old). Phase I, II, and III studies of systemic therapy for advanced STS published in the English language were included. After abstract and full text review of 77 studies, 62 trials met inclusion criteria.  Results: The number of clinical trials conducted and published in advanced STS has increased over the last 30 years. Although median OS has increased, attempts at improving first line therapy through dose intensification, doublet chemotherapy or alternative backbones have not been successful. The optimal therapy beyond anthracyclines remains a challenge, especially given the inherent heterogeneity of grouping multiple STS subtypes within clinical trials. However, increasing numbers of agents are being studied and several studies had shown isolated PFS or OS benefit.  Conclusions: First line anthracycline systemic therapy remains the standard of care for advanced STS.  However, choice of subsequent therapy beyond anthracyclines remains challenging. Novel systemic therapies, using molecular diagnostics to direct therapy, subtype specific trials and learning from real world retrospective data are all important in improving outcomes for patients with advanced STS.

848 Docetaxel (taxotere) as first line therapy for metastatic or recurrent soft tissue sarcoma (STS): A phase II trial

1995 ◽  
Vol 31 ◽  
pp. S177 ◽  
Author(s):  
M.E. Blackstein ◽  
E.A. Eisenhauer ◽  
V. Bramwell ◽  
K. Belanger ◽  
S. Verma ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Choosing First-Line Therapy for Follicular Lymphoma (FL): A Decision Analysis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 670-670
Author(s):  
Rebecca L. Olin ◽  
Peter A. Kanetsky ◽  
Thomas Ten Have ◽  
Sunita Dwivedy Nasta ◽  
Stephen J. Schuster ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Decision Analysis ◽  
Prescribing Patterns ◽  
Low Grade ◽  
Second Line ◽  
First Line ◽  
Anthracycline Cardiotoxicity ◽  
First Line Therapy ◽  
Line Therapy ◽  
Life Years

Abstract Introduction: There is no standard of care for first-line therapy of low-grade FL. In US practice, the most common strategy is rituximab with combination chemotherapy. However, the optimal choice of regimen remains controversial; options include RCVP, RCHOP and R-Fludarabine-based chemotherapy (RFlu). Because data from randomized clinical trials are not available and unlikely to be generated in the future, we performed a decision analysis comparing RCVP, RCHOP, and RFlu as first-line therapy for FL. Methods: We constructed a Markov model of sequential first- and second-line therapy based on prescribing patterns in the US. The endpoint of the model was quality-adjusted time to tertiary referral for therapy such as RIT or autologous transplant (≥3rd line). A literature review was performed of the Medline database and international meeting abstracts. Clinical trials of both untreated and previously treated patients were systematically evaluated using explicit eligibility criteria. Data were extracted regarding response rates, treatment-related mortality, and progression-free survival (PFS). Weighted estimates were obtained using a fixed effects meta-analysis. The model also incorporated published data on heath state utilities, risk of anthracycline cardiotoxicity and fludarabine-related delayed cytopenias. Primary and sensitivity analyses were performed using TreeAge software. Results: The optimal treatment strategy consisted of RCHOP in first-line followed by RFlu in second-line (9.0 quality-adjusted life years; QALYs). Strategies containing RCVP in either first- or second-line were inferior (6.2–7.7 QALYs). The model was sensitive to first-line PFS of RCHOP and RFlu when these were varied over the range of estimates obtained from individual published trials. The model was robust in sensitivity analysis of most other parameters, including rate of delayed cytopenias after RFlu, anthracycline cardiotoxicity, and quality of life adjustments. Conclusions: Using decision analysis, the optimal first-line therapy for low-grade FL is RCHOP, followed by RFlu in second-line. This strategy maximizes quality-adjusted time to tertiary therapy. Use of RCVP does not improve overall quality-adjusted time relative to more intensive therapies.

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