Adjuvant therapy with imatinib mesylate after resection of primary high-risk gastrointestinal stromal tumors in Japanese patients.

Abstract

BACKGROUND:

Imatinib mesylate, a small-molecule tyrosine kinase inhibitor, is currently used for adjuvant therapy of patients who have undergone resection of high-risk gastrointestinal stromal tumors (GISTs). There are no data concerning the efficacy and safety of postoperative adjuvant therapy with imatinib for Japanese or East Asian patients with GIST.

METHODS:

A single-arm, open-label, multicenter trial was conducted in 17 hospitals in Japan. The eligibility criteria included histologically proven primary high-risk GISTs with macroscopic complete resection. Patients were treated with imatinib at a dose of 400 mg/day for 1 year after surgery. The primary endpoint was recurrence-free survival as assessed by Kaplan-Meier analysis. The secondary endpoints were overall survival and safety. This study was registered with ClinicalTrials.gov, number NCT00171977.

RESULTS:

A total of 64 patients were enrolled between September 2004 and July 2006. The median age of the patients was 59.5 years. Forty-nine (76.6%) patients completed the 1-year treatment, whereas 15 (23.4%) patients did not complete the treatment owing to recurrence, toxicities, and consent withdrawal. At the median follow-up period of 109 weeks, 20 patients had recurrence. The 3-year recurrence rate was 42.7% (95% confidence interval 29.2-56.3%), which exceeded the expected recurrence rate in this trial. The recurrence-free and overall survival rates at 2 years were 71.1 and 93.7%, respectively. The most frequent adverse drug reaction of any grade was eyelid edema (48.4%), followed by neutropenia (40.6%), leukopenia (39.1%), nausea (39.1%), rash (37.5%), and peripheral edema (37.5%), most of which were mild and manageable.

CONCLUSIONS:

Adjuvant therapy with imatinib at 400 mg/day for 1 year is well tolerated by Japanese patients and possibly reduces the risk of early recurrence of high-risk GISTs.

• Authors: Tatsuo Kanda, Toshirou Nishida, Norihito Wada, Osamu Kobayashi, Masakazu Yamamoto, Akira Sawaki, Narikazu Boku, Masato Koseki, Toshihiko Doi, Yasushi Toh, Yoshihiro Kakeji, Toshiro Sugiyama, Yoshito Komatsu, Shojiro Kikuchi, Kyoji Ogoshi, Hitoshi Katai, Kazuhito Miyachi, Seiichi Hirota, Atsushi Ohtsu
• Journal: International journal of clinical oncology (Int J Clin Oncol) Vol. 18 Issue 1 Pg. 38-45 (Feb 2013) ISSN: 1437-7772 [Electronic] Japan
• PMID: 22105894 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzamides
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Imatinib Mesylate

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage)
• Benzamides (administration & dosage, adverse effects)
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Drug-Related Side Effects and Adverse Reactions (chemically induced, classification, physiopathology)
• Female
• Gastrointestinal Stromal Tumors (drug therapy, pathology, surgery)
• Humans
• Imatinib Mesylate
• Japan
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Piperazines (administration & dosage, adverse effects)
• Postoperative Period
• Protein Kinase Inhibitors (adverse effects)
• Pyrimidines (administration & dosage, adverse effects)
• Recurrence
• Treatment Outcome