A phase I study of oxaliplatin and doxorubicin in pediatric patients with relapsed or refractory extracranial non-hematopoietic solid tumors

Authors

  • Leo Mascarenhas MD, MS,

    Corresponding author
    1. Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California
    2. Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California
    • Associate Professor of Pediatrics, Division of Hematology/Oncology, Children's Hospital Los Angeles, 4650, Sunset Boulevard, Mailstop 54, Los Angeles, CA 90027.
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  • Marcio Malogolowkin MD,

    1. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin
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  • Saro H. Armenian DO, MPH,

    1. Department of Pediatrics and Population Sciences, City of Hope National Medical Center, Duarte, California
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  • Richard Sposto PhD,

    1. Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California
    2. Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California
    3. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
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  • Rajkumar Venkatramani MD, MS

    1. Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California
    2. Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California
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  • Conflict of Interest: nothing to report.

Abstract

Background

The combination of a platinum agent and anthracycline has shown activity in pediatric solid tumors. This trial evaluated the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of oxaliplatin combined with doxorubicin in pediatric patients with recurrent solid tumors.

Methods

Oxaliplatin was administered on day 1 and Doxorubicin on days 1–3 of each 21 day course. The study utilized a standard 3 + 3 dose escalation design. Three dose levels were evaluated: (1) oxaliplatin 105 mg/m2 and doxorubicin 20 mg/m2; (2) oxaliplatin 130 mg/m2 and doxorubicin 20 mg/m2; and (3) oxaliplatin 130 mg/m2 and doxorubicin 25 mg/m2. Dexrazoxane was administered at 10 times the doxorubicin dose prior to doxorubicin infusion.

Results

Seventeen patients were enrolled. Dose level 1 was the determined MTD. Grade 2 cardiac DLT was seen in one of six patients on dose level 1, grade 4 thrombocytopenia in two of five patients on dose level 2, and one each of grade 2 cardiac and grade 4 thrombocytopenia in five patients on dose level 3. Cardiac DLT was only noted in patients with prior exposure to both anthracycline and chest radiation. No grade 3 or 4 neurotoxicity or mucositis was seen. Objective responses were noted in two patients with neuroblastoma and one each of mixed germ cell tumor, thymic neuroendocrine carcinoma, and nasopharyngeal carcinoma.

Conclusions

Oxaliplatin 105 mg/m2 on day 1 combined with doxorubicin 20 mg/m2 days 1–3 was the MTD. This combination shows sufficient activity to justify further studies in select pediatric tumors. Pediatr Blood Cancer 2013; 60: 1103–1107. © 2013 Wiley Periodicals, Inc.

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