Recurrent neuroblastoma: Randomized treatment with topotecan + cyclophosphamide (T+C) vs. topotecan alone(T). A POG/CCG Intergroup Study

Frantz, C N; London, Wendy B.; Diller, Lisa; Seeger, R C; Sawyer, Kenneth C.

doi:10.1200/jco.2004.22.14_suppl.8512

Cited by 7 publications

(3 citation statements)

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“…The incorporation of novel drug combinations with documented activity against relapsed neuroblastoma may be one way of achieving this goal. Approximately one-third of patients with first recurrence of neuroblastoma will achieve a complete or partial response with cyclophosphamide and topotecan [Frantz et al, 2004]. A recent pilot study demonstrated the feasibility of incorporating cyclophosphamide and topotecan into induction chemotherapy in newly diagnosed patients [Park et al, 2006], and the efficacy of this approach is now being studied in a large Phase III trial through the Children's Oncology Group (COG).…”

Section: Agents Currently In Clinical Trials Conventional Cytotoxic Tmentioning

confidence: 99%

New therapeutic targets for the treatment of high‐risk neuroblastoma

Wagner

Danks

2009

J of Cellular Biochemistry

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High-risk neuroblastoma remains a major problem in pediatric oncology, accounting for 15% of childhood cancer deaths. Although incremental improvements in outcome have been achieved with the intensification of conventional chemotherapy agents and the addition of 13-cis-retinoic acid, only one-third of children with high-risk disease are expected to be long-term survivors when treated with current regimens. In addition, the cost of cure can be quite high, as surviving children remain at risk for additional health problems related to long-term toxicities of treatment. Further advances in therapy will require the targeting of tumor cells in a more selective and efficient way so that survival can be improved without substantially increasing toxicity. In this review we summarize ongoing clinical trials and highlight new developments in our understanding of the molecular biology of neuroblastoma, emphasizing potential targets or pathways that may be exploitable therapeutically.

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Section: Agents Currently In Clinical Trials Conventional Cytotoxic Tmentioning

confidence: 99%

New therapeutic targets for the treatment of high‐risk neuroblastoma

Wagner

Danks

2009

J of Cellular Biochemistry

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“…The collision of the advancing DNA replication fork with the drug-enzyme-DNA complex produces irreversible double-stranded DNA breaks that result in cell cycle arrest and apoptotic cell death (Masuda et al, 1996). Based on encouraging results in patients with recurrent disease (Frantz et al, 2004), the combination of topotecan and cyclophosphamide is now being incorporated into frontline therapy (Park et al, 2008). Both topotecan and the related camptothecin agent irinotecan have demonstrated schedule-dependent activity against neuroblastoma xenografts (Houghton et al, 1995).…”

Section: Introductionmentioning

confidence: 98%

Pediatric Neuroblastoma: Treatment with Oral Irinotecan and Temozolomide

Wagner

2011

Pediatric Cancer

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New strategies are needed to improve outcomes for children with high-risk neuroblastoma, as fewer than half of these patients are expected to survive with current therapies. The combination of temozolomide and irinotecan has recently been evaluated in cooperative group studies for patients with relapsed high-risk neuroblastoma. This combination is attractive given the reported single-agent activity of each drug, their non-overlapping toxicity profiles, and the preclinical evidence of synergy in mouse models of neuroblastoma. Clinical trials involving 120 patients with relapsed or refractory neuroblastoma have shown the combination to produce responses or sustained disease stabilization in a significant subset of patients. In addition, the tolerability of the regimen may allow it to serve as a therapeutic backbone on which to add targeted agents. Finally, use of orally administered irinotecan given on shorter treatment schedules can reduce costs and improve patient convenience.

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“…Topotecan in combination regimens with other agents active in neuroblastoma, such as cyclophosphamide, cisplatin, and etoposide, have been reported. A phase-I study of topotecan with cyclophosphamide showed that the maximum tolerated dose of topotecan was 0.75 mg/m 2 day -1 when given with a daily dose of 250 mg/m 2 day -1 of cyclophosphamide for 5 days (Saylors et al 1998).A phase-II window study showed a significant response rate in newly diagnosed pa-tients, and the results are pending for a recently completed randomized study (P9462) in the Children's Oncology Group in relapse patients, comparing topotecan alone at 2 mg/m 2 day -1 to the combined regimen of cyclophosphamide with topotecan (Frantz et al 2004). Preclinical studies suggest that other cytotoxic agents, such as vincristine (Thompson et al 1999) or MGI114 (iludin; Weitman et al 2000), might provide synergistic cytotoxicity with topotecan.…”

Section: Topotecanmentioning

confidence: 99%

Treatment of Relapsed and Refractory Neuroblastoma

Matthay¹,

Kushner²

Pediatric Oncology

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Recurrent neuroblastoma: Randomized treatment with topotecan + cyclophosphamide (T+C) vs. topotecan alone(T). A POG/CCG Intergroup Study

Cited by 7 publications

References 0 publications

New therapeutic targets for the treatment of high‐risk neuroblastoma

New therapeutic targets for the treatment of high‐risk neuroblastoma

Pediatric Neuroblastoma: Treatment with Oral Irinotecan and Temozolomide

Treatment of Relapsed and Refractory Neuroblastoma

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