Gefitinib in combination with oral topotecan and cyclophosphamide in relapsed neuroblastoma: Pharmacological rationale and clinical response
| Autor: | Alessandro Jenkner, Aurora Castellano, Heather P. McDowell, Alberto Donfrancesco, Ilaria Ilari, Maria Debora De Pasquale, Carlo Dominici, Clementina De Laurentis, Maria Antonietta De Ioris, Samantha Cialfi |
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| Rok vydání: | 2009 |
| Předmět: |
Oncology
Chemotherapy medicine.medical_specialty Cyclophosphamide business.industry medicine.medical_treatment Phases of clinical research Hematology Neutropenia Pharmacology medicine.disease Gefitinib Internal medicine Neuroblastoma Pediatrics Perinatology and Child Health medicine heterocyclic compounds Topotecan business Progressive disease medicine.drug |
| Zdroj: | Pediatric Blood & Cancer. 54:55-61 |
| ISSN: | 1545-5009 |
| Popis: | Aim Activity and toxiciy of gefitinib in combination with topotecan and cyclophosphamide (CPA) were evaluated in a case-series of relapsed neuroblastoma (NB) patients. The in vitro activity of the combination was also assessed. Procedure Gefitinib (250 mg/day), topotecan (0.8 mg/m2/day), and CPA (50 mg/m2/day) (GTC) were administered orally for 14 consecutive days out of 28 days. Antitumor activity of gefitinib as single agent and in combination with either topotecan or CPA was assessed in a panel of NB cell lines. Results Ninety-two courses were given in 10 patients. Grade 4 neutropenia was observed in 7/92 courses (8%) and grade 4 thrombocytopenia in 8/92 (9%). Two patients had a grade 2 liver toxicity, four a grade 1/2 skin toxicity, and two a grade 1/2 diarrhea. Dose reduction of topotecan and/or CPA was required in eight patients. After four courses, three patients were in partial response (PR) and four with a stable disease (SD), while three experienced a progressive disease (PD). Time to progression (TTP) was 9 months (range, 1–27). After a median follow-up of 16 months (range 5–54), seven patients are died of disease (DOD) and three alive with disease (AWD). All but one patient discontinued oral chemotherapy because of a PD, whilst one patient stopped chemotherapy after 27 months with a SD. In vitro, gefitinib was synergistic with topotecan and additive with CPA. Conclusion The GTC combination was well tolerated and the TTP was encouraging. These promising results, also supported by in vitro evidence, should be further confirmed in a phase II study. Pediatr Blood Cancer 2010; 54:55–61. © 2009 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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