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/m(2)/day), and CPA (50 mg/m(2)/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. Copyright 2009 Wiley-Liss, Inc.
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/m(2)/day), and CPA (50 mg/m(2)/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. Copyright 2009 Wiley-Liss, Inc.
Authors: Wayne L Furman; Lisa M McGregor; M Beth McCarville; Mihaela Onciu; Andrew M Davidoff; Sandy Kovach; Dana Hawkins; Valerie McPherson; Peter J Houghton; Catherine A Billups; Jianrong Wu; Clinton F Stewart; Victor M Santana Journal: Invest New Drugs Date: 2011-07-28 Impact factor: 3.850
Authors: James Keller; Anjaruwee S Nimnual; Mathew S Varghese; Kristen A VanHeyst; Michael J Hayman; Edward L Chan Journal: Mol Cancer Res Date: 2016-05-23 Impact factor: 5.852
Authors: Federica Saletta; Carol Wadham; David S Ziegler; Glenn M Marshall; Michelle Haber; Geoffrey McCowage; Murray D Norris; Jennifer A Byrne Journal: BBA Clin Date: 2014-06-28