The addition of cixutumumab or temozolomide to intensive multiagent chemotherapy is feasible but does not improve outcome for patients with metastatic rhabdomyosarcoma1: A report from the Children's Oncology Group. Issue 2 (23rd October 2018)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Cancer. Volume 125:Issue 2(2019)
• Page Start: 290
• Page End: 297
• Publication Date: 2018-10-23
• Subjects: insulin‐like growth factor 1 receptor (IGF‐1R) -- metastatic sarcoma -- monoclonal antibody -- pediatric sarcoma -- rhabdomyosarcoma; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.31770
• Languages: English
• ISSNs: 0008-543X

Abstract

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. Abstract : The addition of cixutumumab or temozolomide to intensive multiagent chemotherapy for metastatic rhabdomyosarcoma is safe and feasible. Neither agent improves outcomes compared with the chemotherapy backbone alone.