A Prognostic Score to Guide Appropriate Delivery of First Line Palliative Chemotherapy for Advanced Soft Tissue Sarcoma

2012 ◽  
Vol 23 ◽  
pp. ix485 ◽  
N. Gough ◽  
C. Smith ◽  
J.R. Ross ◽  
J. Riley ◽  
I. Judson
2015 ◽  
Vol 5 (1) ◽  
Nadia Yousaf ◽  
Samuel Harris ◽  
Juan Martin-Liberal ◽  
Susannah Stanway ◽  
Mark Linch ◽  

Cancer ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 1585-1591 ◽  
Vasilios Karavasilis ◽  
Beatrice M. Seddon ◽  
Susan Ashley ◽  
Omar Al-Muderis ◽  
Cyril Fisher ◽  

Sarcoma ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-19 ◽  
Julian F. Guest ◽  
Monica Panca ◽  
Erikas Sladkevicius ◽  
Nicholas Gough ◽  
Mark Linch

Background. Doxorubicin/ifosfamide is a first-line systemic chemotherapy for the majority of advanced soft tissue sarcoma (ASTS) subtypes. Trabectedin is indicated for the treatment of ASTS after failure of anthracyclines and/or ifosfamide; however it is being increasingly used off-label as a first-line treatment. This study estimated the cost effectiveness of these two treatments in the first-line management of ASTS in Italy, Spain, and Sweden.Methods. A Markov model was constructed to estimate the cost effectiveness of doxorubicin/ifosfamide compared to trabectedin monotherapy, defined as the cost per QALY gained, in each country.Results. First-line treatment with doxorubicin/ifosfamide resulted in lower two-year healthcare costs and more QALYs than first-line treatment with trabectedin monotherapy in all three countries. Probabilistic sensitivity analysis showed that at a cost per QALY threshold of €35,000, >90% of a cohort would be cost effectively treated with doxorubicin/ifosfamide compared to trabectedin monotherapy in all three countries.Conclusion. Within the model’s limitations, first-line treatment of patients with ASTS with doxorubicin/ifosfamide instead of trabectedin monotherapy affords a cost-effective use of publicly funded healthcare resources in Italy, Spain, and Sweden and is therefore the preferred treatment in all three countries. These findings support the recommendation that trabectedin should remain a second-line treatment.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. TPS11591-TPS11591
Erlinda Maria Gordon ◽  
Victoria S. Chua-Alcala ◽  
Katherine Kim ◽  
Shiva Sreenath Andrali ◽  
Marie Del Rosario ◽  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9563-9563
J. M. Siehl ◽  
E. Thiel ◽  
A. Schmittel ◽  
G. Hütter ◽  
U. Keilholz

9563 Objectives: The current first line standard chemotherapy for advanced soft-tissue sarcomas is the combination of doxorubicine and ifosfamide. Liposomal encapsulation is a strategy pursued to reduce toxicity and improve tumor uptake. There are so far only limited systematic data regarding the efficacy of liposomal anthracyclines in advanced soft-tissue sarcomas. We have previously reported on a phase II study with liposomal daunorubicine (L-Dauno) with ifosfamide, named IDx1. Here we report on an additional cohort of the phase II study using liposomal doxorubicine (L-Doxo). Methods: In a single-arm two cohort phase II study 55 patients with advanced soft-tissue sarcoma had received first line a maximum of 6 cycles (median 2 cycles) of ifosphamide (5 g/m2) and in cohort 1 L-Dauno (100 mg/m2, 40 patients) or in cohort 2 the approximate equivalent of L-Doxo (75 mg/m2, 15 patients). Cycles were repeated every 4 weeks in absence of disease progression. Primary study endpoint was response rate. Results: The overall response rate was 25% (n = 14). In the L-Dauno group the results were as follows: CR 3% (n = 1), PR 29% (n = 10), SD 17% (n = 6), PD 37% (n = 13), NED or intermittent death 14% (n = 5), and in the L-Doxo group: PR 20% (n =3), SD 26% (n =4) and PD 53% (n = 8). Interestingly, all three liposarcoma patients (two in the L-Dauno group, one in the L-Doxo group) responded, whereas liposarcoma usually carries a poor response rate. For both combinations toxicity was similarly tolerable with short episodes of hematotoxicity (leucocyte nadir on day 9, platelet nadir on day 11), 11 febrile episodes, no grade 3 or 4 mucositis, no cardiac toxicity and 5 episodes of grade 2 acute ifosfamide-related CNS-toxicity. Based on the hematotoxicity kinetics, three weekly regimens appear feasible. Conclusion: The combination of liposomal anthracyclines and ifosfamide is a safe and effective first line regimen in the treatment for advanced soft tissue sarcoma. Further evaluation in a randomized trial will be pursued. The unexpected high responsiveness of liposarcoma warrants further phase II investigation. 1Siehl JM et al. Cancer 2005. No significant financial relationships to disclose.

ESMO Open ◽  
2021 ◽  
Vol 6 (5) ◽  
pp. 100258
E. Younger ◽  
R.L. Jones ◽  
D. den Hollander ◽  
V.L.M.N. Soomers ◽  
I.M.E. Desar ◽  

2014 ◽  
Vol 32 (29) ◽  
pp. 3299-3306 ◽  
Sant P. Chawla ◽  
Lee D. Cranmer ◽  
Brian A. Van Tine ◽  
Damon R. Reed ◽  
Scott H. Okuno ◽  

Purpose TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability. Patients and Methods In this open-label phase II study, TH-302 300 mg/m2 was administered intravenously on days 1 and 8 with doxorubicin 75 mg/m2 on day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302. Results Ninety-one patients initiated TH-302 plus doxorubicin induction treatment. The PFS rate at 6 months (primary efficacy measure) was 58% (95% CI, 46% to 68%). Median PFS was 6.5 months (95% CI, 5.8 to 7.7 months); median overall survival was 21.5 months (95% CI, 16.0 to 26.2 months). Best tumor responses were complete response (n = 2 [2%]) and partial response (n = 30 [34%]). During TH-302 maintenance (n = 48), five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were fatigue, nausea, and skin and/or mucosal toxicities as well as anemia, thrombocytopenia, and neutropenia. These were less severe and less frequent during maintenance. There was no evidence of TH-302–related hepatic, renal, or cardiac toxicity. Conclusion PFS, overall survival, and tumor response compared favorably with historical outcomes achieved with other first-line chemotherapies for advanced STS. A phase III study of TH-302 is ongoing (NCT01440088).

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