Pilot study of topotecan and high-dose cyclophosphamide for resistant pediatric solid tumors Journal Article
| Authors: | Kushner, B. H.; Kramer, K.; Meyers, P. A.; Wollner, N.; Cheung, N. K. V. |
| Article Title: | Pilot study of topotecan and high-dose cyclophosphamide for resistant pediatric solid tumors |
| Abstract: | Background. The recommended dosages of topotecan and cyclophosphamide in combination for prior-treated patients - 3.75 mg/m2 and 1,250 mg/m2 in children, 5 mg/m2 and 600 mg/m2 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/m2 by 48 hr infusion, and topotecan 6 mg/m2 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 ≥3 (n = 9) cycles of HD-Cy/Topo. All patients had previously received ≥ 6 cycles of other therapy, high-dose alkylator-based chemotherapy, and/or etoposide- and doxorubicin-containing regimens. H D-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. (C) 2000 Wiley-Liss, Inc. |
| Keywords: | adolescent; adult; child; clinical article; controlled study; child, preschool; clinical trial; cancer recurrence; salvage therapy; cisplatin; doxorubicin; cancer combination chemotherapy; drug efficacy; drug safety; solid tumor; topotecan; antineoplastic agent; treatment indication; carboplatin; controlled clinical trial; bone marrow suppression; etoposide; antineoplastic combined chemotherapy protocols; alkylating agent; cyclophosphamide; vincristine; clinical protocol; antineoplastic activity; drug effect; ifosfamide; childhood cancer; sarcoma; neuroblastoma; pilot projects; thrombocyte count; dactinomycin; leukocyte count; mesna; granulocyte colony stimulating factor; outpatient care; retreatment; tumor resistance; drug induced disease; clinical examination; humans; human; male; female; priority journal; article |
| Journal Title: | Medical and Pediatric Oncology |
| Volume: | 35 |
| Issue: | 5 |
| ISSN: | 0098-1532 |
| Publisher: | Wiley Liss |
| Date Published: | 2000-11-01 |
| Start Page: | 468 |
| End Page: | 474 |
| Language: | English |
| DOI: | 10.1002/1096-911x(20001101)35:5<468::aid-mpo5>3.0.co;2-p |
| PUBMED: | 11070479 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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