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.


METHODS
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.


CONCLUSIONS
The combination of thalidomide and cyclophosphamide as described herein has a modest and tolerable toxicity profile but little evidence of efficacy.
Gilheeney
Stephen W
SW
Departments of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Lyden
David C
DC
Sgouros
Shirley
S
Antunes
Nuno
N
Gerald
William
W
Kramer
Kim
K
Lis
Eric
E
Meyers
Paul
P
Rosen
Nancy
N
Thaler
Howard T
HT
Trippett
Tanya
T
Wexler
Leonard
L
Dunkel
Ira J
IJ
D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D003520:Cyclophosphamide