Thiotepa/topotecan/carboplatin with autologous stem cell rescue in recurrent/refractory/poor prognosis pediatric malignancies of the central nervous system Journal Article

  

Authors:	Gilheeney, S. W.; Khakoo, Y.; Souweidane, M.; Wolden, S.; Boulad, F.; Dunkel, I. J.
Article Title:	Thiotepa/topotecan/carboplatin with autologous stem cell rescue in recurrent/refractory/poor prognosis pediatric malignancies of the central nervous system
Abstract:	Background. Thiotepa and carboplatin are known to be active in central nervous system tumors. Topotecan potentiates the anticancer effects of alkylators and crosses the blood-brain barrier. We present ten patients with recurrent or progressive central nervous system malignancies treated on a myeloablative regimen using these drugs. Methods. Treatment included: Thiotepa 300 mg/m2 on days -8, -7, and -6; topotecan 2 mg/m2 on days -8, -7, -6, -5, and -4; and carboplatin ∼500 mg/m2 (Calvert formula - area under the curve=7) on days -5, -4, and -3. Stem cell rescue was on day 0. Results. Age at study entry ranged from 2.5 to 20 years old (median age 8.7 years). Five had medulloblastoma (MB), four had high grade glioma (HGG), and one had trilateral retinoblastoma/pineoblastoma (tRB/PB). Prior treatment for all patients included surgery and chemotherapy (1-7 regimens, median 2). Nine patients received radiotherapy; one patient did not receive radiotherapy pre-study. Three patients had residual disease at the time of transplant. There were two toxic deaths. Four patients are event-free survivors at a median of 6 years (range 2.8-7.6 years) after treatment including 2/5 MB patients, 1/4 HGG patients, and the tRB/PB patient. Four of the seven patients with no evidence of disease/minimal residual disease status at the time of stem cell rescue are long-term survivors versus 1/3 with measurable disease. Conclusion. Thiotepa/topotecan/ carboplatin may help consolidate remission of poor prognosis pediatric central nervous system tumors. Diagnosis and extent of disease prior to stem cell rescue may have an impact on outcome. © 2009 Wiley-Liss, Inc.
Keywords:	adolescent; adult; child; clinical article; preschool child; school child; treatment outcome; child, preschool; cancer surgery; young adult; neutropenia; area under the curve; cancer combination chemotherapy; hypophosphatemia; side effect; cancer radiotherapy; combined modality therapy; chemotherapy; topotecan; drug megadose; neurotoxicity; recurrent cancer; glioma; cancer grading; carboplatin; drug eruption; liver toxicity; nephrotoxicity; neoplasm recurrence, local; anemia; gastrointestinal symptom; mucosa inflammation; thrombocytopenia; antineoplastic combined chemotherapy protocols; autologous stem cell transplantation; creatinine blood level; hematopoietic stem cell transplantation; retinoblastoma; cancer mortality; thiotepa; central nervous system tumor; childhood cancer; cancer survivor; central nervous system neoplasms; lymphocytopenia; hyperkalemia; hypokalemia; hyponatremia; cancer regression; myeloablative conditioning; minimal residual disease; glioblastoma; medulloblastoma; granulocyte colony stimulating factor; astrocytoma; recurrent glioma; pediatrics; hypocalcemia; recurrent medulloblastoma; pineoblastoma
Journal Title:	Pediatric Blood and Cancer
Volume:	54
Issue:	4
ISSN:	1545-5009
Publisher:	Wiley Periodicals, Inc
Date Published:	2010-04-01
Start Page:	591
End Page:	595
Language:	English
DOI:	10.1002/pbc.22347
PUBMED:	19998470
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-77649150719&partnerID=40&md5=65954770203eb132bb10db06f95aecf5
Notes:	--- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: PBCEA" - "Source: Scopus"

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