Phase I study of oral cyclophosphamide and oral topotecan for children with recurrent or refractory solid tumors.
BACKGROUND
To determine the maximum-tolerated duration and dose-limiting toxicity of a daily schedule of orally administered cyclophosphamide and topotecan in pediatric patients with recurrent or refractory malignant solid tumors.


METHODS
Patients received oral cyclophosphamide (50 mg/m2/dose) in the morning followed by topotecan (0.8 mg/m2/dose) 8-12 hr later for an escalating number of consecutive days (10, 14, and 17 days).


RESULTS
Seventeen pediatric patients were treated with oral cyclophosphamide and topotecan for durations of 10-17 days for a total of 58 treatment courses. Reversible hematologic toxicity (neutropenia and thrombocytopenia) was the dose-limiting toxicity. Nonhematologic toxicities of greater than grade 3 were not observed. A partial response (neuroblastoma following myeloablative chemotherapy and stem cell rescue) and prolonged stable disease (medulloblastoma) were each observed in one patient.


CONCLUSIONS
The recommended duration of therapy with a daily schedule of both oral cyclophosphamide (50 mg/m2/day) and topotecan (0.8 mg/m2/day) for previously treated pediatric patients with recurrent or refractory solid tumors is 14 consecutive days. The observed dose limiting toxicity (DLT) was reversible neutropenia. This regimen was well tolerated in heavily pretreated patients and demonstrated activity against recurrent pediatric solid tumors.
Bowers
Daniel C
DC
Department of Pediatrics, UT Southwestern Medical Center at Dallas, Dallas, Texas 75390-9063, USA. Daniel.Bowers@utsouthwestern.edu
Aquino
Victor M
VM
Leavey
Patrick J
PJ
Bash
Robert O
RO
Journeycake
Janna M
JM
Tomlinson
Gail
G
Mulne
Arlynn F
AF
Haynes
Heidi J
HJ
Winick
Naomi J
NJ
D000284:Administration, Oral; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy*; D016879:Salvage Therapy; D019772:Topotecan / Q000008:administration & dosage
D019772:Topotecan; D003520:Cyclophosphamide