Phase III trial of standard versus dose-intensified doxorubicin, ifosfamide and dacarbazine (MAID) in the first-line treatment of metastatic and locally advanced soft tissue sarcoma

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.

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Outcome of First-Line Treatment of Elderly Advanced Soft Tissue Sarcoma (Sts) Patients: a Pooled Analysis of Eleven Eortc Soft Tissue and Bone Sarcoma Group Trials

Annals of Oncology ◽

10.1093/annonc/mdu354.4 ◽

2014 ◽

Vol 25 ◽

pp. iv495 ◽

Cited By ~ 1

Author(s):

W.T.A. van der Graaf ◽

A. Le Cesne ◽

O. Mir ◽

H. Gelderblom ◽

A. Italiano ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Bone Sarcoma ◽

Pooled Analysis ◽

Line Treatment ◽

First Line ◽

Advanced Soft Tissue Sarcoma ◽

First Line Treatment

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A phase II study of anlotinib in the first-line treatment of locally advanced or metastatic soft tissue sarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e23531 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e23531-e23531

Author(s):

Xin Huang ◽

Zhaoming Ye ◽

Tao Li ◽

Yongzhong Wei ◽

Shoufeng Wang ◽

...

Keyword(s):

Clinical Trial ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Disease Control ◽

Interim Analysis ◽

Locally Advanced ◽

Line Treatment ◽

First Line ◽

Metastatic Soft Tissue Sarcoma ◽

First Line Treatment

e23531 Background: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. We assessed if anlotinib, a multitarget tyrosine kinase inhibitor, is efficacy and safety for the first-line treatment of these patients. Methods: This is an open-label, single-arm, multicenter, phase II clinical trial (NCT03792542) including 44 planned subjects. Eligible patients were aged 18-70 years old, diagnosed with locally advanced or metastatic soft-tissue sarcoma and had at least one measurable lesion according to RECIST 1.1. Other inclusion criteria included ECOG PS 0̃2, chemotherapy and anti-angiogenesis treatment naïve. Patients were administrated 12mg anlotinib once daily for 14 days every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Safety assessment was done in patients who received at least one dose of anlotinib. Here we report the results of a planned interim analysis. Results: From April 2019 to December 2020, 29 patients (16 males and 13 females) were enrolled from 7 hospitals in China. The median age is 57 (range 23-69). Pathological types included liposarcoma (n = 8), undifferentiated pleomorphic sarcoma (n = 5), fibrosarcoma (n = 5), synovial sarcoma (n = 4), and others (n = 7). At the data cutoff date on December 31, 2020, the median duration of treatment was 5.3 months, and the median PFS was not reached. 26 patients were eligible for the evaluation of tumor response.1 achieved partial response (PR) and the objective response rate (ORR) was 3.85% (1/26). 24 had stale disease (SD) and the disease control rate (DCR) was 96.2% (25/26). The clinical benefit rate (CBR), defined as the proportion of patients who achieved durable disease control (CR/PR/SD) more than 4 and 6 months, were 65.4% (17/26) and 38.5% (10/26) respectively. Most adverse events (AE) were grade 1 or 2. The most common grade 3 AE was hypertension (17.2%). No grade 4 AEs or treatment related death occurred in this study through the last follow-up. Conclusions: This interim analysis showed anlotinib of promising efficacy and favorable tolerance in the first-line treatment of locally advanced or metastatic soft- tissue sarcoma. Clinical trial information: NCT03792542.

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EPAZ: A randomized phase II trial comparing pazopanib with doxorubicin as first line treatment in elderly patients with metastatic or advanced soft tissue sarcoma of the Working Group Medical Oncology (AIO) and German Interdisciplinary Sarcoma Group (GISG).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.tps10576 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. TPS10576-TPS10576

Author(s):

Viktor Gruenwald ◽

Annegret Kunitz ◽

Markus Kajo Schuler ◽

Hans-Georg Kopp ◽

Bernd Kasper ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Elderly Patients ◽

Medical Oncology ◽

Phase Ii Trial ◽

Line Treatment ◽

First Line ◽

Advanced Soft Tissue Sarcoma ◽

Randomized Phase Ii ◽

First Line Treatment

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A Phase I/II Study of a 72-h Continuous Infusion of Etoposide in Advanced Soft Tissue Sarcoma

Sarcoma ◽

10.1080/13577149778236 ◽

1997 ◽

Vol 1 (3-4) ◽

pp. 149-154 ◽

Cited By ~ 3

Author(s):

Charles R. Crawley ◽

Ian R. Judson ◽

Mark Verrill ◽

Catherine Hill ◽

Florence I. Raynaud

Keyword(s):

Steady State ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Single Agent ◽

Locally Advanced ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Dose Limiting Toxicity ◽

First Line Treatment

Purpose. The study was performed to assess the antitumour activity and toxicity of a 72-h continuous infusion of single-agent etoposide as second-line treatment for patients with locally advanced or metastatic soft tissue sarcoma (STS), following reports of substantial activity using this schedule of etoposide administration as first-line treatment in combination with ifosfamide.Patients/method. This was an open phase I/II trial performed at a single institution in patients with metastatic or locally advanced STS who had failed first-line treatment with doxorubicin + ifosfamide combination chemotherapy or, less commonly, single-agent treatment with doxorubicin or ifosfamide. Etoposide was given as a continuous intravenous infusion over 72 h. The starting dose level was 200 mgm−2day−1× 3 escalating in 10% steps in cohorts of three patients until dose-limiting toxicity was encountered.Results. Seventeen patients were treated, median age 47 years (range 26–71 years). No responses were seen in 16 assessable patients despite etoposide levels in the cotoxic range. The steady-state plasma concentration exceeded 8μg ml−1in all patients and in patients treated at ≥ 600 mg m−2the mean steady-state level was 14.4μg ml−1. The median event-free survival was 6 weeks (95% confidence interval (CI) 3.31–8.69) and the overall survival 16 weeks (95% CI 9.28–22.72). The maximum tolerated dose in this pretreated patient group was 200 mg m−2day−1× 3. The dose-limiting toxicity was myelosuppression.Discussion. Etoposide given by 72-h infusion is inactive as second-line chemotherapy in STS. It is associated with significant toxicity when given in these doses, in this patient group.

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