Prospective phase II trial of pazopanib plus CapeOX (capecitabine and oxaliplatin) in previously untreated patients with advanced gastric cancer

Seung Tae Kim, Jeeyun Lee, Su Jin Lee, Se Hoon Park, Sin-Ho Jung, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Joon Oh Park, Seung Tae Kim, Jeeyun Lee, Su Jin Lee, Se Hoon Park, Sin-Ho Jung, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Joon Oh Park

Abstract

We designed a single-arm, open label phase II study to determine the efficacy and toxicity of the combination of pazopanib with CapeOx (capecitabine and oxaliplatin) in metastatic /recurrent advanced gastric cancer (AGC) patients. Previously untreated AGC patients received capecitabine (850 mg/m2 bid, day 1-14) plus oxaliplatin (130 mg/m2, day 1) in combination with pazopanib (800 mg, day 1-21) every three weeks. Treatment was continued until progression of the disease or intolerable toxicity was observed. In all, 66 patients were treated with pazopanib plus CapeOx. The median age of the patients was 51.5 years (range, 23.0-77), and the median ECOG performance status was 1 (0-1). Among all 66 patients, one complete response and 37 partial responses were observed (overall response rate, 62.4%; 95% confidence interval (CI), 45.7-73.5% accounting for the 2-stage design of this trial). Stable disease was observed in 23 patients (34.8%), revealing a 92.4% disease control rate. The median progression free survival and overall survival were 6.5 months (95% CI, 5.6-7.4) and 10.5 months (95% CI, 8.1-12.9), respectively. Thirty-four patients (51.5%) experienced a treatment-related toxicity of grade 3 or more. The most common toxicities of grade 3 or more were neutropenia (15.1%), anemia (10.6%), thrombocytopenia (10.6%), anorexia (7.6%), nausea (3.0%), and vomiting (3.0%). There were no treatment-related deaths. The combination of pazopanib and CapeOx showed moderate activity and an acceptable toxicity profile as a first-line treatment in metastatic / recurrent AGC patients (ClinicalTrials.gov NCT01130805).

Keywords: capecitabine; gastric cancer; oxaliplatin; pazopanib.

Conflict of interest statement

Pazopanib was kindly provided by GlaxoSmithKline for this study. Clinical research grants were supported by GlaxoSmithKline (J.O.Park) and Sanofi (J.O.Park). Other authors have no potential conflicts of interest to declare.

Figures

Figure 1. Maximum best change in tumor…
Figure 1. Maximum best change in tumor size from baseline
Decreased in best percent change from baseline = 100%. Red bar complete response, Blue bar partial response, Green bar stable disease, Yellow bar progressive disease.
Figure 2. PFS of AGC patients treated…
Figure 2. PFS of AGC patients treated with pazopanib and CapeOx
PFS progression-free survival, AGC advanced gastric cancer, CI confidence interval, CapeOx capecitabine and oxaliplatin.
Figure 3. OS of AGC patients treated…
Figure 3. OS of AGC patients treated with pazopanib and CapeOx
OS overall survival, AGC advanced gastric cancer, CI confidence interval, CapeOx capecitabine and oxaliplatin.

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