Phase I Study of Axitinib in Combination with Cisplatin and Capecitabine in Patients with Previously Untreated Advanced Gastric Cancer.
- Author:
Do Youn OH
1
;
Toshihiko DOI
;
Kuniaki SHIRAO
;
Keun Wook LEE
;
Sook Ryun PARK
;
Ying CHEN
;
Liqiang YANG
;
Olga VALOTA
;
Yung Jue BANG
Author Information
- Publication Type:Clinical Trial ; Original Article
- Keywords: Axitinib; Stomach neoplasms; Cisplatin; Capecitabine; Pharmacokinetics; Clinical trial; Phase I
- MeSH: Acute Kidney Injury; Aortic Aneurysm, Abdominal; Appetite; Cisplatin*; Cohort Studies; Disease-Free Survival; Fluorouracil; Humans; Hypertension; Maximum Tolerated Dose; Pharmacokinetics; Stomach Neoplasms*; Stomatitis; Thrombocytopenia
- From:Cancer Research and Treatment 2015;47(4):687-696
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: This phase I trial evaluated the question of whether the standard starting dose of axitinib could be administered in combination with therapeutic doses of cisplatin/capecitabine in patients with previously untreated advanced gastric cancer, and assessed overall safety, pharmacokinetics, and preliminary antitumor activity of this combination. MATERIALS AND METHODS: Patients in dose level (DL) 1 received axitinib 5 mg twice a day (days 1 to 21) with cisplatin 80 mg/m2 (day 1) and capecitabine 1,000 mg/m2 twice a day (days 1 to 14) in 21-day cycles. Maximum tolerated dose (MTD) was the highest dose at which < or = 30% of the first 12 patients experienced a dose-limiting toxicity (DLT) during cycle 1. Ten additional patients were enrolled and treated at the MTD in order to obtain additional safety and pharmacokinetic data. RESULTS: Three DLTs occurred during cycle 1 in three (25%) of the first 12 patients: ruptured abdominal aortic aneurysm, acute renal failure, and > 5 consecutive days of missed axitinib due to thrombocytopenia. DL1 was established as the MTD, since higher DL cohorts were not planned. Common grade 3/4 non-hematologic adverse events in 22 patients treated at DL1 included hypertension (36.4%) and decreased appetite and stomatitis (18.2% each). Cisplatin/capecitabine slightly increased axitinib exposure; axitinib decreased capecitabine and 5-fluorouracil exposure. Eight patients (36.4%) each had partial response or stable disease. Median response duration was 9.1 months; median progression-free survival was 3.8 months. CONCLUSION: In patients with advanced gastric cancer, standard doses of axitinib plus therapeutic doses of cisplatin and capecitabine could be administered in combination. Adverse events were manageable.
