Sunitinib in combination with gemcitabine plus cisplatin for advanced non-small cell lung cancer: A phase I dose-escalation study

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• 作者：Martin Reck ; Norbert Frickhofen ; Susana Cedres ; Ulrich Gatzemeier ; David Heigener ; Heinz-Georg Fuhr ; Aron Thall ; Silvana Lanzalone ; Patricia Stephenson ; Ana Ruiz-Garcia ; Richard Chao ; Enriqueta Felip
• 关键词：Non-small cell lung cancer ; Sunitinib ; Gemcitabine ; Cisplatin
• 刊名：Lung Cancer
• 出版年：2010
• 出版时间：November 2010
• 年：2010
• 卷：70
• 期：2
• 页码：180-187
• 全文大小：209 K

文摘

Purpose

To determine the maximum tolerated dose (MTD) of sunitinib plus gemcitabine/cisplatin for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). Safety, pharmacokinetics, and antitumor activities were evaluated.

Methods

Patients ≥18 years with Eastern Cooperative Oncology Group performance status 0/1 and stage IIIB/IV NSCLC were included in this open-label, multicenter, dose-escalation phase I study. Treatment was administered in 3-week cycles: oral sunitinib 37.5 or 50 mg/day intermittently (Schedule 2/1: 2 weeks on treatment, 1 week off treatment) or 25 mg continuous daily dosing (CDD) schedule with intravenous infusions of gemcitabine (1000 or 1250 mg/m² days 1, 8) and cisplatin (80 mg/m² day 1).

Results

A total of 28 evaluable patients were assigned to four dose levels. Most adverse events (AEs) on the Schedule 2/1 MTD were mild to moderate. Dose delays due to myelosuppression occurred on both schedules, limiting treatment to a median of four cycles. Four of 18 evaluable patients (22 % ) on Schedule 2/1 and 1 of 6 patients (17 % ) on the CDD schedule had confirmed partial responses.

Conclusions

The MTD was identified as sunitinib 37.5 mg (Schedule 2/1), gemcitabine 1250 mg/m², and cisplatin 80 mg/m², with most AEs being mild to moderate. However, frequent dose delays due to myelosuppression occurred. There was evidence of antitumor activity with this combination.