Phase I study of topotecan for pediatric patients with malignant solid tumors.
OBJECTIVE
To determine the dose-limiting toxicity and potential efficacy of topotecan in pediatric patients with refractory malignant solid tumors.


METHODS
In this phase I clinical trial, 27 patients received topotecan 0.75-1.9 mg/m2 by continuous intravenous infusion daily for 3 days. Fifty-three treatment courses were given to these patients.


RESULTS
Myelosuppression was the dose-limiting toxicity at levels of 1.3 to 1.9 mg/m2 for 3 days, requiring significant support with transfused packed RBCs and platelets. Myelosuppression was variable in severity at the 1.0-mg/m2 dosage level; thus, additional patients were treated with this dosage, followed by human recombinant granulocyte-colony stimulating factor (G-CSF). Other toxicities were not significant. One patient with neuroblastoma had a complete response that lasted for 8 months. Stable disease activity was recorded for other patients with neuroblastoma, rhabdomyosarcoma, and islet cell carcinoma. Pharmacokinetic studies showed that topotecan plasma concentrations ranged from 1.6 to 7.5 ng/mL during infusions of 1.0 mg/m2/d, and that there was a biphasic plasma distribution with a mean terminal half-life of 2.9 +2- 1.0 hours.


CONCLUSIONS
Topotecan is a promising anticancer agent that deserves phase II testing in pediatric solid tumors. We recommend that pediatric phase II topotecan trials use 1.0 mg/m2/d for 3 days as a constant intravenous infusion, followed by G-CSF for 14 days, and that these treatment courses be repeated every 21 days.
Pratt
C B
CB
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN 38101-0318.
Stewart
C
C
Santana
V M
VM
Bowman
L
L
Furman
W
W
Ochs
J
J
Marina
N
N
Kuttesch
J F
JF
Heideman
R
R
Sandlund
J T
JT
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006207:Half-Life; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019772:Topotecan; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D019772:Topotecan; D002166:Camptothecin