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

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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

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temozolomide
Rhabdomyosarcoma
Drug Therapy
irinotecan
Vincristine
Cyclophosphamide
Confidence Intervals
anti-IGF-1R antibody A12
Ifosfamide
Cytotoxins
Dactinomycin
Somatomedins
Etoposide

Keywords

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

PubMed: MeSH publication types

  • Journal Article

Cite this

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

In: Cancer, Vol. 125, No. 2, 15.01.2019, p. 290-297.

Research output: Contribution to journalArticle

Malempati, S, Weigel, BJ, Chi, YY, Tian, J, Anderson, JR, Parham, DM, Teot, LA, Rodeberg, DA, Yock, TI, Shulkin, BL, Spunt, SL, Meyer, WH & Hawkins, DS 2019, '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', Cancer, vol. 125, no. 2, pp. 290-297. https://doi.org/10.1002/cncr.31770
Malempati, Suman ; Weigel, Brenda J ; Chi, Yueh Yun ; Tian, Jing ; Anderson, James R. ; Parham, David M. ; Teot, Lisa A. ; Rodeberg, David A. ; Yock, Torunn I. ; Shulkin, Barry L. ; Spunt, Sheri L. ; Meyer, William H. ; Hawkins, Douglas S. / 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. In: Cancer. 2019 ; Vol. 125, No. 2. pp. 290-297.
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title = "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",
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.",
keywords = "insulin-like growth factor 1 receptor (IGF-1R), metastatic sarcoma, monoclonal antibody, pediatric sarcoma, rhabdomyosarcoma",
author = "Suman Malempati and Weigel, {Brenda J} and Chi, {Yueh Yun} and Jing Tian and Anderson, {James R.} and Parham, {David M.} and Teot, {Lisa A.} and Rodeberg, {David A.} and Yock, {Torunn I.} and Shulkin, {Barry L.} and Spunt, {Sheri L.} and Meyer, {William H.} and Hawkins, {Douglas S.}",
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T1 - The addition of cixutumumab or temozolomide to intensive multiagent chemotherapy is feasible but does not improve outcome for patients with metastatic rhabdomyosarcoma

T2 - A report from the Children’s Oncology Group

AU - Malempati, Suman

AU - Weigel, Brenda J

AU - Chi, Yueh Yun

AU - Tian, Jing

AU - Anderson, James R.

AU - Parham, David M.

AU - Teot, Lisa A.

AU - Rodeberg, David A.

AU - Yock, Torunn I.

AU - Shulkin, Barry L.

AU - Spunt, Sheri L.

AU - Meyer, William H.

AU - Hawkins, Douglas S.

PY - 2019/1/15

Y1 - 2019/1/15

N2 - 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.

AB - 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.

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KW - metastatic sarcoma

KW - monoclonal antibody

KW - pediatric sarcoma

KW - rhabdomyosarcoma

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