Donfrancesco Alberto, De Ioris Maria Antonietta, McDowell Heather Prudence, De Pasquale Maria Debora, Ilari Ilaria, Jenkner Alessandro, Castellano Aurora, Cialfi Samantha, De Laurentis Clementina, Dominici Carlo
Division of Oncology, Ospedale Pediatrico Bambino Gesù (IRCCS), Rome, Italy.
Pediatr Blood Cancer. 2010 Jan;54(1):55-61. doi: 10.1002/pbc.22219.
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.
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.
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.
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.
在一组复发性神经母细胞瘤（NB）患者中评估吉非替尼联合拓扑替康和环磷酰胺（CPA）的活性及毒性。同时也评估了该联合用药的体外活性。
吉非替尼（250毫克/天）、拓扑替康（0.8毫克/平方米/天）和CPA（50毫克/平方米/天）（GTC）在28天中连续口服14天。在一组NB细胞系中评估了吉非替尼作为单药以及与拓扑替康或CPA联合用药的抗肿瘤活性。
10名患者共接受了92个疗程的治疗。92个疗程中有7个（8%）出现4级中性粒细胞减少，8个（9%）出现4级血小板减少。2名患者出现2级肝毒性，4名出现1/2级皮肤毒性，2名出现1/2级腹泻。8名患者需要减少拓扑替康和/或CPA的剂量。四个疗程后，3名患者部分缓解（PR），4名病情稳定（SD），3名病情进展（PD）。疾病进展时间（TTP）为9个月（范围1 - 27个月）。中位随访16个月（范围5 - 54个月）后，7名患者死于疾病（DOD），3名带瘤生存（AWD）。除1名患者外，所有患者均因疾病进展停止口服化疗，1名患者在病情稳定27个月后停止化疗。在体外，吉非替尼与拓扑替康协同，与CPA相加。
GTC联合用药耐受性良好，TTP令人鼓舞。这些有前景的结果，也得到了体外证据的支持，应在II期研究中进一步证实。
