Phase I trial of cisplatin and topotecan in children with recurrent solid tumors: Children's Cancer Group Study 0942.
OBJECTIVE
To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cisplatin after a 72-hour continuous infusion of topotecan.


METHODS
Thirty-six children younger than age 22 years (range 3-21) with recurrent solid tumors were treated with cisplatin 45 to 75 mg/m2 infused over the course of 6 hours, followed by a 72-hour continuous infusion of topotecan 0.75 or 1 mg/m2 per day, followed by granulocyte colony stimulating factor (G-CSF), either immediately after treatment or when neutropenia developed. Patients were stratified by the presence of bone marrow tumor involvement and previous radiation to the bone marrow.


RESULTS
The DLT was neutropenia (absolute neutrophil count <500/microL for >7 days). The MTD was cisplatin 60 mg/m2 and topotecan 1 mg/m2 per day followed by G-CSF starting 24 hours after chemotherapy for patients without marrow involvement or previous radiation to the bone marrow. An acceptable MTD was not found for patients with previous radiation to the bone marrow or bone marrow involvement or without the use of G-CSF starting 24 hours after chemotherapy was completed. Topotecan clearance and steady-state levels were determined. Limited evidence for antitumor activity with this combination was found in rhabdomyosarcoma.


CONCLUSIONS
The recommended dose for phase II trials is cisplatin 60 mg/m2 followed by a 72-hour infusion of topotecan 1 mg/m2 per day with G-CSF starting 24 hours after the completion of topotecan.
Wells
Robert J
RJ
Children's Hospital Research Foundation, Cincinnati, Ohio, USA. robert.wells@chmcc.org
Reid
Joel M
JM
Ames
Matthew M
MM
Mares
Wen Lieu
WL
Krailo
Mark D
MD
Seibel
Nita L
NL
Mosher
Revonda
R
Reaman
Gregory H
GH
Wiersma
Susan R
SR
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D009503:Neutropenia / Q000139:chemically induced* / Q000188:drug therapy; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000532:radiotherapy; D016879:Salvage Therapy; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
D016179:Granulocyte Colony-Stimulating Factor; D019772:Topotecan; D002945:Cisplatin