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 Anticancer Agents
Gastric Cancer
Therapy
Biological Therapy
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.