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Phase 1 study of high-dose DFMO, celecoxib, cyclophosphamide and topotecan for patients with relapsed neuroblastoma: a New Approaches to Neuroblastoma Therapy trial.
Hogarty, Michael D; Ziegler, David S; Franson, Andrea; Chi, Yueh-Yun; Tsao-Wei, Denice; Liu, Kangning; Vemu, Rohan; Gerner, Eugene W; Bruckheimer, Elizabeth; Shamirian, Anasheh; Hasenauer, Beth; Balis, Frank M; Groshen, Susan; Norris, Murray D; Haber, Michelle; Park, Julie R; Matthay, Katherine K; Marachelian, Araz.
Afiliación
  • Hogarty MD; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. hogartym@chop.edu.
  • Ziegler DS; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. hogartym@chop.edu.
  • Franson A; Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, NSW, Australia.
  • Chi YY; School of Women's and Children's Health, University of New South Wales, Sydney, Australia.
  • Tsao-Wei D; Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia.
  • Liu K; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Vemu R; Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
  • Gerner EW; Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
  • Bruckheimer E; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Shamirian A; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Hasenauer B; Cancer Prevention Pharmaceuticals, Tucson, AZ, USA.
  • Balis FM; Panbela Pharmaceuticals, Inc., Waconia, MN, USA.
  • Groshen S; Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
  • Norris MD; Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
  • Haber M; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Park JR; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • Matthay KK; Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
  • Marachelian A; Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, NSW, Australia.
Br J Cancer ; 130(5): 788-797, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38200233
ABSTRACT

BACKGROUND:

MYC genes regulate ornithine decarboxylase (Odc) to increase intratumoral polyamines. We conducted a Phase I trial [NCT02030964] to determine the maximum tolerated dose (MTD) of DFMO, an Odc inhibitor, with celecoxib, cyclophosphamide and topotecan.

METHODS:

Patients 2-30 years of age with relapsed/refractory high-risk neuroblastoma received oral DFMO at doses up to 9000 mg/m2/day, with celecoxib (500 mg/m2 daily), cyclophosphamide (250 mg/m2/day) and topotecan (0.75 mg/m2/day) IV for 5 days, for up to one year with G-CSF support.

RESULTS:

Twenty-four patients (median age, 6.8 years) received 136 courses. Slow platelet recovery with 21-day courses (dose-levels 1 and 2) led to subsequent dose-levels using 28-day courses (dose-levels 2a-4a). There were three course-1 dose-limiting toxicities (DLTs; hematologic; anorexia; transaminases), and 23 serious adverse events (78% fever-related). Five patients (21%) completed 1-year of therapy. Nine stopped for PD, 2 for DLT, 8 by choice. Best overall response included two PR and four MR. Median time-to-progression was 19.8 months, and 3 patients remained progression-free at >4 years without receiving additional therapy. The MTD of DFMO with this regimen was 6750 mg/m2/day.

CONCLUSION:

High-dose DFMO is tolerable when added to chemotherapy in heavily pre-treated patients. A randomized Phase 2 trial of DFMO added to chemoimmunotherapy is ongoing [NCT03794349].
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Recurrencia Local de Neoplasia / Neuroblastoma Tipo de estudio: Clinical_trials Límite: Adolescent / Adult / Child / Child, preschool / Humans Idioma: En Revista: Br J Cancer Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Recurrencia Local de Neoplasia / Neuroblastoma Tipo de estudio: Clinical_trials Límite: Adolescent / Adult / Child / Child, preschool / Humans Idioma: En Revista: Br J Cancer Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido