A phase II trial of thalidomide and cyclophosphamide in patients with recurrent or refractory pediatric malignancies

Background Previous clinical and pre-clinical research has demonstrated synergy between anti-angiogenic agents and cytotoxic chemotherapy. This trial was undertaken to investigate whether the combination of cyclophosphamide and thalidomide would be active against pediatric tumors. Procedure Patients with pediatric malignancies who had no remaining conventional therapeutic options were recruited from January 1999 to May 2001. They received thalidomide (6–12 mg/kg po every day; maximum daily dose 800 mg) and cyclophosphamide (1,200 mg/m2 IV every 28 days). Results Twenty-seven patients were enrolled on the study. Seventeen were male and 10 were female. Median age at the time of registration was 15 years (range 1–54 years). The median number of prior treatment regimens was four. Twenty-one patients were evaluable for response; 1 had a partial response (Hodgkin disease), 1 demonstrated stable disease (neuroendocrine tumor), and 19 had progressive disease. The most common toxicities were hematological (leukocytopenia and neutropenia) and gastrointestinal. One patient experienced a grade 3 rash. Fatigue and daytime somnolence were variable. No peripheral neuropathy was observed. Conclusion The combination of thalidomide and cyclophosphamide as described herein has a modest and tolerable toxicity profile but little evidence of efficacy. Pediatr Blood Cancer 2007;49:261–265. © 2006 Wiley-Liss, Inc.