The addition of cixutumumab or temozolomide to intensive multiagent chemotherapy is feasible but does not improve outcome for patients with metastatic rhabdomyosarcoma: A report from the Children’s Oncology Group

Suman Malempati, Brenda J. Weigel, Yueh Yun Chi, Jing Tian, James R. Anderson, David M. Parham, Lisa A. Teot, David A. Rodeberg, Torunn I. Yock, Barry L. Shulkin, Sheri L. Spunt, William H. Meyer, Douglas S. Hawkins

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

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/m 2 ) 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.

Original languageEnglish (US)
Pages (from-to)290-297
Number of pages8
JournalCancer
Volume125
Issue number2
DOIs
StatePublished - Jan 15 2019

Bibliographical note

Funding Information:
David M. Parham reports grants from the National Cancer Institute during the conduct of the study. Lisa A. Teot reports grants from the National Cancer Institute during the conduct of the study. Douglas S. Hawkins is an uncompensated (other than travel-related expenses) member of the medical advisory boards of Bayer, Loxo Oncology, Celgene, and Bristol-Myers Squibb Oncology. The remaining authors made no disclosures.

Funding Information:
James R. Anderson reports grants from the Cancer Therapy Evaluation Program/National Cancer Institute during the conduct of the study and receives a salary from Merck and Company outside the submitted work. David M. Parham reports grants from the National Cancer Institute during the conduct of the study.

Funding Information:
This work was supported by Children’s Oncology Group grants U10CA180886, U10CA180899, U10CA098543, and U10CA098413 and by St. Baldrick’s Foundation.

Publisher Copyright:
© 2018 American Cancer Society

Keywords

  • insulin-like growth factor 1 receptor (IGF-1R)
  • metastatic sarcoma
  • monoclonal antibody
  • pediatric sarcoma
  • rhabdomyosarcoma

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