Phase I trial of cisplatin and topotecan in children with recurrent solid tumors: Children's Cancer Group study 0942

Robert J. Wells, Joel M Reid, Matthew M. Ames, Wen Lieu Mares, Mark D. Krailo, Nita L. Seibel, Revonda Mosher, Gregory H. Reaman, Susan R. Wiersma

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objectives: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cisplatin after a 72-hour continuous infusion of topotecan. Patients and 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/μL 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.

Original languageEnglish (US)
Pages (from-to)89-93
Number of pages5
JournalJournal of Pediatric Hematology/Oncology
Volume24
Issue number2
DOIs
StatePublished - 2002

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Topotecan
Cisplatin
Bone Marrow
Granulocyte Colony-Stimulating Factor
Maximum Tolerated Dose
Neoplasms
Radiation
Neutropenia
Drug Therapy
Rhabdomyosarcoma
Neutrophils
Bone and Bones

Keywords

  • Cisplatin
  • Phase I trial
  • Topotecan

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Oncology
  • Hematology

Cite this

Phase I trial of cisplatin and topotecan in children with recurrent solid tumors : Children's Cancer Group study 0942. / Wells, Robert J.; Reid, Joel M; Ames, Matthew M.; Mares, Wen Lieu; Krailo, Mark D.; Seibel, Nita L.; Mosher, Revonda; Reaman, Gregory H.; Wiersma, Susan R.

In: Journal of Pediatric Hematology/Oncology, Vol. 24, No. 2, 2002, p. 89-93.

Research output: Contribution to journalArticle

Wells, Robert J. ; Reid, Joel M ; Ames, Matthew M. ; Mares, Wen Lieu ; Krailo, Mark D. ; Seibel, Nita L. ; Mosher, Revonda ; Reaman, Gregory H. ; Wiersma, Susan R. / Phase I trial of cisplatin and topotecan in children with recurrent solid tumors : Children's Cancer Group study 0942. In: Journal of Pediatric Hematology/Oncology. 2002 ; Vol. 24, No. 2. pp. 89-93.
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AU - Wells, Robert J.

AU - Reid, Joel M

AU - Ames, Matthew M.

AU - Mares, Wen Lieu

AU - Krailo, Mark D.

AU - Seibel, Nita L.

AU - Mosher, Revonda

AU - Reaman, Gregory H.

AU - Wiersma, Susan R.

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