700P - A phase I dose-finding study of vorinostat (V) combined with capecitabine (X) and cisplatin (P) as first-line therapy in patients with advanced gast...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Anti-Cancer Agents & Biologic Therapy
Gastric Cancer
Presenter Changhoon Yoo
Authors C. Yoo1, M.H. Ryu2, B. Ryoo1, D.H. Koo1, I. Park1, Y. Kang3
  • 1Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 2Division Of Oncology, Dept Of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 3Dept. Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR

Abstract

Background

The purpose of this trial is to determine the recommended dose (RD) of vorinostat (V), a histone deacetylase inhibitor, in combination with capecitabine (X) and cisplatin (P) and to explore feasibility of V-XP at the RD in advanced gastric cancer.

Patients and methods

The standard 3 + 3 method was used to determine the RD of 3-weekly V-XP during the first cycle. The doses of X (days 1-14, p.o.), P (day 1, i.v.), and V (days 1-14, p.o.) were escalated as following scheme; X 1,600 mg/m2/day, P 60 mg/m2, V 300 mg/day in level 1; X 1,600 mg/m2/day, P 60 mg/m2, V 400 mg/day in level 2A; X 2,000 mg/m2/day, P 60 mg/m2, V 300 mg/day in level 2B; X 2,000 mg/m2/day, P 60 mg/m2, V 400 mg/day in level 3; X 2,000 mg/m2/day, P 80 mg/m2, V 400 mg/day in level 4.

Results

A total of 24 patients were enrolled. Median age was 50 years (range, 25-66), and 11 (46%) were male. Dose limiting toxicity (DLT) was noted in 1 of 6 in level 1 (Grade 4 thrombocytopenia), 0 of 3 in level 2A, 1 of 6 in level 2B (Grade 3 fatigue), 1 of 6 in level 3 (Grade 3 stomatitis) and 2 of 3 in level 4 (Grade 4 thrombocytopenia, and discontinuation of X or V more than 25% of prescribed dosage due to Grade 3 anorexia and Grade 3 fatigue). Level 4 was maximal tolerated dose, and RD was determined as level 3. Six additional patients were enrolled at level 3 to confirm the feasibility, and DLT was not occurred. In 12 patients who received dose level 3, median 6 cycles (range, 3-10) of chemotherapy were given and most frequent Gr 3/4 toxicities were neutropenia (n = 5, 42%) and anorexia (n = 3, 25%). In overall, the objective responses were confirmed in 9 (47%) out of 19 patients with measurable lesions. With a median follow-up of 9 months, median progression-free survival was 7 months (95% confidence interval, 4 to 10 months), and median overall survival was not reached.

Conclusion

Major DLTs of V-XP were thrombocytopenia, fatigue, anorexia and stomatitis. The 3-weekly schedule of X (2,000 mg/m2/day on day 1-14), P (60 mg/m2 on day 1), and V (400 mg/day on day 1-14) is recommended for further development of this regimen in patients with advanced gastric cancer.

Disclosure

Y. Kang: Research fund from MSD.

All other authors have declared no conflicts of interest.