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Phase I Study of Weekly Oxaliplatin in Relapsed or Refractory Pediatric Solid Malignancies

Birgit Geoerger, François Doz, Jean-Claude Gentet, Michele Mayer, Judith Landman-Parker, Fabienne Pichon, Pascal Chastagner, Hervé Rubie, Didier Frappaz, Anne Le Bouil, Sunil Gupta, Gilles Vassal

From the Institut Gustave-Roussy, Villejuif; Institut Curie, Hopital Saint-Vincent de Paul, and Hopital Trousseau, Paris; Hopital de la Timone, Marseille; Centre Oscar Lambret, Lille; Hopital d’Enfants, Nancy; Hopital Purpan, Toulouse; Centre Léon Bérard, Lyon; Centre Hospitalier Universitaire, Angers, France; and Sanofi-aventis, Malvern, PA

Corresponding author: Birgit Geoerger, MD, PhD, Department of Pediatrics, Institut Gustave-Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, France; e-mail: geoerger{at}igr.fr

Purpose To explore feasibility, maximum-tolerated dose (MTD), and recommended dose (RD) for phase II studies of weekly oxaliplatin for the treatment of relapsed or refractory pediatric solid malignancies.

Patients and Methods Eligible patients were 6 months to 21 years old, had a diagnosis of a solid malignancy, and had experienced treatment failure with at least two or more previous lines of therapy. The phase I study was multicentric, open-label, and nonrandomized. It foresaw two phases: a dose-escalation phase (comprising six levels) to find the RD and an extension at the RD to evaluate the cumulative toxicity. Oxaliplatin was administered intravenously over 2 hours on days 1, 8, and 15 of a 28-day cycle.

Results Forty-five patients were enrolled: 29 patients in the dose-escalation phase and 16 patients in the extension at the RD. Median age was 9.5 years (range, 2.8 to 20.0 years) and 7.8 years (range, 1.8 to 19.2 years), respectively. The dose-limiting toxicities during the first treatment cycle were grade 3 (G3) sepsis at 50 mg/m², G3 dysesthesia at 90 mg/m², and G3 dysesthesia and G3 paresthesia at 110 mg/m², thus the MTD and RD was 90 mg/m². No case of ototoxicity was reported. Stable disease was reported in seven patients (16.3%), and confirmed partial response was observed in two patients (4.7%), one with neuroblastoma and one with osteosarcoma.

Conclusion Oxaliplatin administered in a weekly schedule has an acceptable safety profile, different from cisplatin and carboplatin, and shows activity in children with relapsed or refractory solid tumors, suggesting further investigation in pediatric malignancies.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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