Phase I trial of docetaxel administered as a 1-hour infusion in children with refractory solid tumors: a collaborative pediatric branch, National Cancer Institute and Children's Cancer Group trial.

Blaney, Susan M.; Seibel, Nita L.; O’Brien, Michelle; Reaman, Gregory H.; Berg, Stacey L.; Adamson, Peter C.; Poplack, David G.; Krailo, Mark; Mosher, Revonda B.; Balis, Frank M.

doi:10.1200/jco.1997.15.4.1538

Cited by 76 publications

(54 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, although it has been recognized that a wide range in variation of the paediatric versus adult MTD exists for many antineoplastic agents (Marsoni et al, 1985) which can reflect differences in the intensity of prior chemotherapy, and/or physiological differences in renal function, hepatic metabolism and body composition (Balis et al, 1993), there has been a trend towards a lower paediatric:adult MTD ratio over the past decade, which illustrates the importance of prior therapy in the relative tolerance of new anticancer agents (Carlson et al, 1996). Furthermore, more recent Phase I studies have accrued a second stratum of less heavily pre-treated children (Blaney et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

A phase I study of nolatrexed dihydrochloride in children with advanced cancer. A United Kingdom Children’s Cancer Study Group Investigation

et al. 2001

View full text Add to dashboard Cite

Summary A phase I study of nolatrexed, administered as a continuous 5 day intravenous infusion every 28 days, has been undertaken for children with advanced malignancy. 16 patients were treated at 3 dose levels; 420, 640 and 768 mg/m 2 24 h −1 . 8 patients were evaluable for toxicity. In the 6 patients treated at 768 mg/m 2 24 h −1 , dose-limiting oral mucositis and myelosuppression were observed. Plasma nolatrexed concentrations and systemic exposure, measured in 14 patients, were dose related, with mean AUC values of 36 mg −1 ml −1 min −1 , 50 mg ml −1 min −1 and 80 mg ml −1 min −1 at the 3 dose levels studied. Whereas no toxicity was encountered if the nolatrexed AUC was <45 mg ml −1 min − 1 , Grade 3 or 4 toxicity was observed with AUC values of >60 mg ml −1 min −1 . Elevated plasma deoxyuridine levels, measured as a surrogate marker of thymidylate synthase inhibition, were seen at all of the dose levels studied. One patient with a spinal primitive neuroectodermal tumour had stable disease for 11 cycles of therapy, and in two patients with acute lymphoblastic leukaemia a short-lived 50% reduction in peripheral lymphoblast counts was observed. Nolatrexed can be safely administered to children with cancer, and there is evidence of therapeutic activity as well as antiproliferative toxicity. Phase II studies of nolatrexed in children at the maximum tolerated dose of 640 mg/m 2 24 h −1 are warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

A phase I study of nolatrexed dihydrochloride in children with advanced cancer. A United Kingdom Children’s Cancer Study Group Investigation

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Topotecan and irinotecan are topoisomerase inhibitors that are commonly used for treatment of relapsed neuroblastoma, and both have shown single agent activity in preclinical and clinical studies [99][100][101][102][103][104]. Topotecan is primarily used in combination with cyclophosphamide, and the initial phase II study using cycles of this combination (250 mg/m 2 /day cyclophosphamide and 0.75 mg/m 2 /day topotecan for 5 days each) achieved objective responses in 6 of 13 neuroblastoma patients [105].…”

Section: Treatment -Relapsed and Refractory Neuroblastomamentioning

confidence: 99%

Overview and recent advances in the treatment of neuroblastoma

Whittle

Smith

Doherty

et al. 2017

Expert Review of Anticancer Therapy

311

258

View full text Add to dashboard Cite

Introduction: Children with neuroblastoma have widely divergent outcomes, ranging from cure in >90% of patients with low risk disease to <50% for those with high risk disease. Recent research has shed light on the biology of neuroblastoma, allowing for more accurate risk stratification and treatment reduction in many cases, although newer treatment strategies for children with high-risk and relapsed neuroblastoma are needed to improve outcomes. Areas covered: Neuroblastoma epidemiology, diagnosis, risk stratification, and recent advances in treatment of both newly diagnosed and relapsed neuroblastoma. Expert commentary: The identification of newer tumor targets and of novel cell-mediated immunotherapy agents may lead to novel therapeutic approaches, and clinical trials for regimens designed to target individual genetic aberrations in tumors are underway. A combination of therapeutic modalities will likely be required to improve survival and cure rates for patients with high-risk neuroblastoma.ARTICLE HISTORY

show abstract

“…[3][4][5][6] This activity was confirmed in phase II studies in children with recurrent neuroblastoma, rhabdomyosarcoma, osteosarcoma, and brain tumors. 7,8 A slightly higher dose of topotecan was well tolerated in a phase II investigational window study of ; therefore, a higher dose was used in the study described here.…”

Section: Introductionmentioning

confidence: 99%

Phase II Randomized Comparison of Topotecan Plus Cyclophosphamide Versus Topotecan Alone in Children With Recurrent or Refractory Neuroblastoma: A Children's Oncology Group Study

London

Frantz

Campbell

et al. 2010

JCO

103

107

View full text Add to dashboard Cite

A B S T R A C T PurposeSingle-agent topotecan (TOPO) and combination topotecan and cyclophosphamide (TOPO/CTX) were compared in a phase II randomized trial in relapsed/refractory neuroblastoma. Because responders often underwent further therapies, novel statistical methods were required to compare the long-term outcome of the two treatments. Patients and MethodsChildren with refractory/recurrent neuroblastoma (only one prior aggressive chemotherapy regimen) were randomly assigned to daily 5-day topotecan (2 mg/m 2 ) or combination topotecan (0.75 mg/m 2 ) and cyclophosphamide (250 mg/m 2 ). A randomized two-stage group sequential design enrolled 119 eligible patients. Toxicity and response were estimated. Long-term outcome of protocol therapy was assessed using novel methods-causal inference-which allowed adjustment for the confounding effect of off-study therapies. (CRϩPR, 11 [19%] of 59; P ϭ .081); toxicity was similar. At 3 years, progression-free survival (PFS) and overall survival (OS) were 4% Ϯ 2% and 15% Ϯ 4%, respectively. PFS was significantly better for TOPO/CTX (P ϭ .029); there was no difference in OS. Older age at diagnosis and lack of MYCN amplification predicted increased OS (P Ͻ .05). Adjusting for randomized treatment effect and subsequent autologous stem-cell transplantation, there was no difference between TOPO and TOPO/CTX in terms of the proportion alive at 2 years. Results Seven ConclusionTOPO/CTX was superior to TOPO in terms of PFS, but there was no OS difference. After adjustment for subsequent therapies, no difference was detected in the proportion alive at 2 years. Causal inference methods for assessing long-term outcomes of phase II therapies after subsequent treatment can elucidate effects of initial therapies.

show abstract

Phase I trial of docetaxel administered as a 1-hour infusion in children with refractory solid tumors: a collaborative pediatric branch, National Cancer Institute and Children's Cancer Group trial.

Cited by 76 publications

References 13 publications

A phase I study of nolatrexed dihydrochloride in children with advanced cancer. A United Kingdom Children’s Cancer Study Group Investigation

A phase I study of nolatrexed dihydrochloride in children with advanced cancer. A United Kingdom Children’s Cancer Study Group Investigation

Overview and recent advances in the treatment of neuroblastoma

Phase II Randomized Comparison of Topotecan Plus Cyclophosphamide Versus Topotecan Alone in Children With Recurrent or Refractory Neuroblastoma: A Children's Oncology Group Study

Contact Info

Product

Resources

About