Phase I Clinical Trial of Intrathecal Topotecan in Patients With Neoplastic Meningitis

Blaney, Susan M.; Heideman, Richard L.; Berg, Stacey L.; Adamson, Peter C.; Gillespie, Andy; Geyer, J. Russell; Packer, Roger J.; Matthay, K. K.; Jaeckle, Kurt A.; Cole, Diane E.; Kuttesch, Nancy; Poplack, David G.; Balis, Frank M.

doi:10.1200/jco.2003.04.053

Cited by 93 publications

(61 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…40 Busulfan might prove effective against NB in CNS. 39 Intrathecal treatments with chemotherapy 41,42 and radiolabeled monoclonal antibodies are under investigation, 22,23 but no risk factors have been conclusive for incorporating special prophylactic measures against occult NB in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system

Kushner

Krämer

Modak

et al. 2006

Bone Marrow Transplant

View full text Add to dashboard Cite

We report on a three-drug myeloablative regimen designed to consolidate remission and to prevent central nervous system (CNS) relapse of high-risk neuroblastoma (NB). Sixty-six NB patients received topotecan 2 mg/m 2 / day, Â 4 days; thiotepa 300 mg/m 2 /day, Â 3 days; and carboplatin B500 mg/m 2 /day, Â 3 days. Post-SCT treatments included radiotherapy, immunotherapy, 13-cisretinoic acid, 7oral etoposide. Significant nonhematologic toxicities were mucositis and skin-related in all patients, convulsions in three patients, and cardiac failure and venocclusive disease of liver in one patient each. Grade 2 hepatotoxicity led to truncating cytoreduction in two patients; both later relapsed in brain. Among 46 patients transplanted in first complete/very good partial remission (CR/VGPR), event-free survival is 54% (s.e.78%) at 36 months post-SCT; notable events were three non-NB-related deaths (adenovirus on day þ 9, bowel necrosis at 5 months, multiorgan failure at seven months) and four relapses in brain. Of 12 patients transplanted with evidence of NB, two became long-term event-free survivors and two relapsed in the brain. Of eight patients transplanted in second or greater CR/VGPR, one became a long-term event-free survivor and seven relapsed though not in the CNS. This regimen has manageable toxicity but does not prevent CNS relapse.

show abstract

Section: Discussionmentioning

confidence: 99%

Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system

Kushner

Krämer

Modak

et al. 2006

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…Although intrathecal methotrexate (with or without cytarabine) has been traditionally used, there is no preclinical or clinical evidence to support its use (Chan et al 1989). Other intrathecal agents with documented effect against retinoblastoma include topotecan (Blaney et al 2003;) and thiotepa (Pratt et al 1994;Fisher et al 2002). However, there is no evidence that their use can impact outcome.…”

Section: Metastatic Retinoblastomamentioning

confidence: 96%

Retinoblastoma

2010

Pediatric Oncology

View full text Add to dashboard Cite

“…Since mafosfamide does not require hepatic activation to express an antitumor effect, unlike cyclophosphamide, this agent may be potentially useful as an intrathecal chemotherapy option [103]. The cytotoxic activity of mafosfamide has been demonstrated to be similar to activated cyclophosphamide, 4-hydroxy-peroxycyclophospamide in an in vitro study [104].…”

Section: Mafosfamidementioning

confidence: 98%

Intra-CSF administration of chemotherapy medications

Gabay

Thakkar

Stachnik

et al. 2012

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

Leptomeningeal carcinomatosis is a devastating complication of cancer and is likely increasing in incidence. The combination of widespread neuro-axial spread based on CSF flow and the blood-brain barrier (BBB) has favored immediate local delivery of antineoplastic agents. With the BBB, the leptomeninges can be a sanctuary site to systemic cancers and goal of therapy includes preventing involvement in this space. Current therapies with U.S. Food and Drug Administration (FDA) approval are limited to treat hematologic cancers. Although lacking FDA guidance, a wider array of therapies is available to treat solid tumors. We provide an updated examination on both well-established intra-CSF chemotherapies as well as agents having limited data, but reports of therapeutic benefit.

show abstract

Phase I Clinical Trial of Intrathecal Topotecan in Patients With Neoplastic Meningitis

Abstract: The MTD and recommended phase II dose of IT topotecan in patients who are 3 years or older is 0.4 mg. A phase II trial of IT topotecan in children with neoplastic meningitis is in progress.

Cited by 93 publications

References 7 publications

Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system

Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system

Retinoblastoma

Intra-CSF administration of chemotherapy medications

Contact Info

Product

Resources

About