Early results from Children's Oncology Group (COG) ARST0431: Intensive multidrug therapy for patients with metastatic rhabdomyosarcoma (RMS).

Weigel, Brenda; Lyden, Elizabeth; Anderson, John R.; Galster, A.; Arndt, Carola A.S.; Michalski, J.M.; Hawkins, Douglas S.; Meyer, Wally

doi:10.1200/jco.2010.28.15_suppl.9503

Cited by 21 publications

(14 citation statements)

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“…The ARST0431 regimen included 6 weeks of initial therapy with vincristine and irinotecan (VI); followed by interval‐compressed cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE); 2 subsequent courses of VI with radiation therapy to primary and metastatic sites; and 4 cycles of vincristine, dactinomycin and cyclophosphamide (VAC). Although the early EFS results were encouraging, more mature 3‐year EFS was 38% for all patients but was only 20% for those who had more than 1 risk factor as defined by Oberlin et al (age >10 years or <1 year, unfavorable primary site, 3 or more metastatic sites, and bone or bone marrow involvement) . Hence, intensification of traditional treatment modalities did not improve outcome for the majority of patients with metastatic RMS.…”

Section: Introductionmentioning

confidence: 90%

The addition of cixutumumab or temozolomide to intensive multiagent chemotherapy is feasible but does not improve outcome for patients with metastatic rhabdomyosarcoma

Malempati

Weigel

Yun

et al. 2018

Cancer

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Background The outcome for patients with metastatic rhabdomyosarcoma (RMS) remains poor. A previous Children’s Oncology Group (COG) study (ARST0431) for patients with metastatic RMS produced no improvement in outcome using multiple cytotoxic agents in a dose‐intensive manner. The authors report results from the subsequent COG study (ARST08P1), which evaluated the feasibility and efficacy of adding cixutumumab (insulin‐like growth factor‐1 monoclonal antibody) or temozolomide to the ARST0431 intensive chemotherapy backbone. Methods Two nonrandomized pilot studies were conducted in patients with metastatic RMS, initially to determine feasibility, and both pilots were expanded to assess efficacy. All patients received 54 weeks of chemotherapy, including vincristine/irinotecan, interval‐compressed vincristine/doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide, and vincristine/dactinomycin/cyclophosphamide. In pilot 1, patients received intravenous cixutumumab (3, 6, or 9 mg/kg) once weekly throughout therapy. In pilot 2, patients received oral temozolomide (100 mg/m2) daily for 5 days with irinotecan. All patients received radiation to the primary tumor and to metastatic sites. Results One hundred sixty‐eight eligible patients were enrolled (97 on pilot 1 and 71 on pilot 2). Most patients were aged ≥10 years (73%), with alveolar histology (70%), and had bone and/or bone marrow metastases (59%). Toxicities observed in each pilot were similar to those reported on ARST0431. With a median follow‐up of 2.9 years, the 3‐year event‐free survival rate was 16% (95% confidence interval, 7%‐25%) with cixutumumab and 18% (95% confidence interval, 2%‐35%) with temozolomide. Conclusions The addition of cixutumumab or temozolomide to intensive multiagent chemotherapy for metastatic RMS was safe and feasible. Neither agent improved outcome compared with the same chemotherapy that was used on ARST0431.

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Section: Introductionmentioning

confidence: 90%

The addition of cixutumumab or temozolomide to intensive multiagent chemotherapy is feasible but does not improve outcome for patients with metastatic rhabdomyosarcoma

Malempati

Weigel

Yun

et al. 2018

Cancer

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“…Patients were included in this analysis if they had a diagnosis of embryonal histology (including botryoid and spindle cell variants) and were eligible for and treated in one of these studies (N = 2192). 8–17 Outcome for patients with RMS can be predicted by characteristics of the disease and its presentation at diagnosis. Thus, the analyses that follow were performed separately for patients in the low, intermediate, and high prognostic risk strata.…”

Section: Methodsmentioning

confidence: 99%

The World Health Organization Classification of Skeletal Muscle Tumors in Pediatric Rhabdomyosarcoma: A Report From the Children's Oncology Group

Rudzinski

Anderson²,

Hawkins³

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

141

101

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Context Since 1995, the International Classification of Rhabdomyosarcoma has provided prognostically relevant classification for rhabdomyosarcoma (RMS) and allowed risk stratification for children with RMS. The International Classification of Rhabdomyosarcoma includes botryoid and spindle cell RMS as superior-risk groups, embryonal RMS as an intermediate-risk group, and alveolar RMS as an unfavorable-risk group. The 2013 World Health Organization (WHO) classification of skeletal muscle tumors modified the histologic classification of RMS to include sclerosing RMS as a type of spindle cell RMS separate from embryonal RMS. The current WHO classification includes embryonal, alveolar, spindle cell/sclerosing, and pleomorphic subtypes of RMS and does not separate the botryoid subtype. Objective To determine if the WHO classification applies to pediatric RMS. Design To accomplish this goal, we reviewed 9 consecutive Children’s Oncology Group clinical trials to compare the WHO and International Classification of Rhabdomyosarcoma classifications with outcome and site of disease. Results Except for a subset of low-risk RMS, the outcome for botryoid was not significantly different from typical embryonal RMS when analyzed by primary site. Similarly, pediatric spindle cell and sclerosing patterns of RMS did not appear significantly different from typical embryonal RMS, with one exception: spindle cell RMS in the parameningeal region had an inferior outcome with 28% event-free survival. Conclusion Our data support use of the WHO RMS classification in the pediatric population, with the caveat that histologic diagnosis does not necessarily confer the same prognostic information in children as in adults.

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“…It also incorporated interval-compressed VDC/IE, which COG AEWS0031 showed improved outcome for localized Ewing sarcoma [90]. Even after adjusting for prognostic groups within patients with metastatic disease, the EFS on ARST0431 was superior to prior COG and international studies [13], particularly for patients with more ''favorable'' metastatic disease, including ERMS and those with lower metastatic risk scores as defined by Oberlin [23]. ARST0431 provided a backbone onto which temozolomide and IMC-A12 are being added in ARST08P1.…”

Section: Major Recent Findings Rhabdomyosarcomamentioning

confidence: 99%

“…However, pre-clinical models predicted that another topoisomerase I inhibitor, irinotecan, would be more effective than topotecan [40,41,43]. The clinical activity of irinotecan, particularly when combined with vincristine (as predicted by xenograft models [44]) was confirmed in ARST0121 (phase II study of recurrent RMS) [45] and in D9802 and ARST0431, both phase II window studies of metastatic RMS [23,46]. The 70% response rate on D9802 was the highest ever seen in a phase II window including other drug pairs [46,47], supporting the current intermediate-risk RMS study, ARST0531 (VAC AE irinotecan).…”

Section: Molecular Targets: Rmsmentioning

confidence: 99%

Children's Oncology Group's 2013 blueprint for research: Soft tissue sarcomas

Hawkins

Spunt

Skapek

2012

Pediatric Blood & Cancer

165

158

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In the US, approximately 850-900 children are diagnosed each year with soft tissue sarcomas (STS). Key findings from recent clinical trials include safe reduction in therapy for low risk rhabdomyosarcoma (RMS), validation of FOXO1 fusion as a prognostic factor, a modest improvement in outcome for high-risk RMS, and a biologically-designed non-cytotoxic therapy for pediatric desmoid tumor. Planned Phase 2 trials include targeted agents for VEGF/PDGF, mTOR, and IGF-1R for children with RMS and VEGF for children with non-RMS STS (NRSTS). For RMS, COG Phase 3 trials potentially will explore VEGF/mTOR inhibition or chemotherapy interval compression. For NRSTS, a COG Phase 3 trial will explore VEGF inhibition.

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Early results from Children's Oncology Group (COG) ARST0431: Intensive multidrug therapy for patients with metastatic rhabdomyosarcoma (RMS).

Cited by 21 publications

References 0 publications

The addition of cixutumumab or temozolomide to intensive multiagent chemotherapy is feasible but does not improve outcome for patients with metastatic rhabdomyosarcoma

The addition of cixutumumab or temozolomide to intensive multiagent chemotherapy is feasible but does not improve outcome for patients with metastatic rhabdomyosarcoma

The World Health Organization Classification of Skeletal Muscle Tumors in Pediatric Rhabdomyosarcoma: A Report From the Children's Oncology Group

Children's Oncology Group's 2013 blueprint for research: Soft tissue sarcomas

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