Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2022 Sep;69(9):e29691.
doi: 10.1002/pbc.29691. Epub 2022 Apr 19.

Long-term results from the multicentric European randomized phase 3 trial CWS/RMS-96 for localized high-risk soft tissue sarcoma in children, adolescents, and young adults

Monika Sparber-Sauer  1   2 , Andrea Ferrari  3 , Daniel Kosztyla  4 , Ruth Ladenstein  5   6 , Giovanni Cecchetto  7 , Bernarda Kazanowska  8 , Giovanni Scarzello  9 , Gustaf Ljungman  10 , Giuseppe Maria Milano  11 , Felix Niggli  12 , Rita Alaggio  13   14 , Christian Vokuhl  15 , Michela Casanova  3 , Thomas Klingebiel  16   17   18   19 , Angelica Zin  20 , Ewa Koscielniak  1   2 , Gianni Bisogno  21
Affiliations
Clinical Trial

Long-term results from the multicentric European randomized phase 3 trial CWS/RMS-96 for localized high-risk soft tissue sarcoma in children, adolescents, and young adults

Monika Sparber-Sauer et al. Pediatr Blood Cancer. 2022 Sep.

Abstract

Background: CWS/RMS-96 was an international multicenter trial with randomization between two therapy arms of the standard four-drug therapy (vincristine, ifosfamide, adriamycin, dactinomycin [VAIA]) versus an intensified six-drug regimen (carboplatin, epirubicin, vincristine, dactinomycin, ifosfamide, and etoposide [CEVAIE]) for high-risk rhabdomyosarcoma (RMS), extraskeletal Ewing sarcoma (EES), and undifferentiated sarcoma (UDS) in children, adolescents, and young adults aiming to improve their survival. Intensified chemotherapy with CEVAIE did not improve outcome.

Methods: Patients younger than 21 years with a previously untreated localized HR-RMS, EES, and UDS were enrolled from Cooperative Weichteilsarkom Studiengruppe (CWS) centers in Germany, Austria, Poland, Switzerland, and from Italian Soft Tissue Sarcoma Committee (STSC) centers. Randomization (1:1) to receive either 9 × 21 days cycles of VAIA or CEVAIE was performed separately in CWS and STSC. Hyperfractionated accelerated radiotherapy (32-44.8 Gy) was added at week 9-12 according to histology and response to chemotherapy. A secondary microscopically complete nonmutilating resection was performed if possible. Primary endpoints were response to chemotherapy, event-free (EFS) and overall survival (OS).

Results: Five hundred fifty-seven patients (HR-RMS: n = 416, EES and UDS: n = 141) underwent randomization: VAIA (n = 273) or CEVAIE (n = 284). Radiotherapy was given to 70% of patients in both groups. A secondary resection was performed in 47% and 48% patients, respectively. The 5-year EFS and OS for the VAIA and CEVAIE treatment arms were 59.8% and 60.8% (p = .89), and 74.2% and 68.3% (p = .16), respectively. No differences in response, toxicity, or second malignancies emerged in the two groups.

Conclusion: The use of an intensified regimen failed to show a significant improvement in tumor response and outcome of patients with localized HR-RMS, EES, and UDS.

Keywords: CEVAIE; CWS-96; RMS-96; VAIA; high-risk soft tissue sarcoma; randomization; rhabdomyosarcoma.

PubMed Disclaimer

References

REFERENCES

    1. Steliarova-Foucher E, Stiller C, Kaatsch P, et al. Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since the 1970s (the ACCIS project): an epidemiological study. Lancet. 2004;364(9451):2097-2105.
    1. Kaatsch P, Spix J. German Childhood Cancer Registry - Annual Report 2003 (1980-2002). Deutsches Kinderkrebsregister; 2003.
    1. Stevens MC. Treatment for childhood rhabdomyosarcoma: the cost of cure. Lancet Oncol. 2005;6(2):77-84.
    1. Crist W, Gehan EA, Ragab AH, et al. The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol. 1995;13(3):610-630.
    1. Crist WM, Anderson JR, Meza JL, et al. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001;19(12):3091-3102.

Publication types

LinkOut - more resources