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Med Pediatr Oncol. 2000 Nov;35(5):468-74.

Pilot study of topotecan and high-dose cyclophosphamide for resistant pediatric solid tumors.

Author information

1
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. kushnerb@mskcc.org

Abstract

BACKGROUND:

The recommended dosages of topotecan and cyclophosphamide in combination for prior-treated patients-3.75 mg/m(2) and 1,250 mg/m(2) in children, 5 mg/m(2) and 600 mg/m(2) in adults, respectively-are well below those of each agent when used singly. We tested the hypothesis that much higher dosing would meet critical goals of salvage therapy: antitumor effect and a lack of toxicity to key organs, so as not to preclude subsequent consolidative treatments needed for cure.

PROCEDURE:

Patients with resistant pediatric solid tumors received cyclophosphamide 4,200 mg/m(2) by 48 hr infusion, and topotecan 6 mg/m(2) by 72 hr infusion (HD-Cy/Topo). Mesna and granulocyte colony-stimulating factor were used. Cycles were repeated when neutrophil counts were >1,000/uL and platelet counts were >75,000/uL.

RESULTS:

Twenty-eight patients, aged 2 to 33 years (median, 14), received one (n = 4), two (n = 15), or > or =3 (n = 9) cycles of HD-Cy/Topo. All patients had previously received > or =6 cycles of other therapy, high-dose alkylator-based chemotherapy, and/or etoposide- and doxorubicin-containing regimens. HD-Cy/Topo was given in an outpatient setting. Profound myelosuppression was the major toxicity, but retreatment was possible by day 28, and preliminary results with peripheral blood stem cell collections showed a sparing effect on hemopoietic stem cells. Mucositis was uncommon. After HD-Cy/Topo, cardiac, renal, hepatic, and pulmonary function remained within the normal range. Partial or minor responses were noted in neuroblastoma, desmoplastic small round-cell tumor, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.

CONCLUSIONS:

Its antitumor potential and limited toxicity make HD-Cy/Topo an attractive choice for inclusion in aggressive salvage programs aimed at achieving cures of resistant tumors. It may also merit incorporation into frontline treatment protocols.

PMID:
11070479
[Indexed for MEDLINE]
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