Efficacy and safety profile of imatinib mesylate (ST1571) in Japanese patients with advanced gastrointestinal stromal tumors: a phase II study (STI571B1202).
BACKGROUND
Imatinib mesylate, an inhibitor of KIT, ABL protein, and platelet-derived growth factor receptor alpha (PDGFRalpha) tyrosine kinase, has recently been found to have a dramatic antitumor effect on gastrointestinal stromal tumor (GIST). The aim of this study was to assess the efficacy and safety of imatinib mesylate in Japanese patients with advanced GIST.


METHODS
Patients with measurable lesions were enrolled between April 1, 2002, and September 20, 2002, using a design based on previous phase II studies in the United States and the European Union. The diagnosis of GIST was proven histologically with positive immunostaining for KIT (CD117). Imatinib mesylate was administered at a dose of either 400 mg or 600 mg once a day. Pharmacokinetic parameters and mutation analysis of c-kit were also assessed in a subgroup of patients.


RESULTS
A total of 74 patients (28 receiving imatinib mesylate at 400 mg/day; 46 receiving 600 mg/day); median age, 56.0 years, were enrolled. No patient had a complete response, 51 patients (69%) had a partial response, and 19 patients (26%) had stable disease. The median progression-free survival time was 96 weeks. The estimated 3-year overall survival (Kaplan-Meier) rate for all patients was 73.6%. The most frequent adverse effects related to the drug were nausea (78%), diarrhea (70%), dermatitis (62%), facial edema (61%), edema of the lower limbs (58%), vomiting (54%), and eyelid edema (51%). Most of the adverse effects were mild and manageable.


CONCLUSIONS
Imatinib mesylate is generally safe and has significant activity in the treatment of advanced GIST in Japanese patients.
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. toshin@surg1.med.osaka-u.ac.jp
Toshirou
T
Nishida
Kuniaki
K
Shirao
Akira
A
Sawaki
Masato
M
Koseki
Takeshi
T
Okamura
Atsushi
A
Ohtsu
Toshiro
T
Sugiyama
Kunihisa
K
Miyakawa
Seiichi
S
Hirota
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides; D018572:Disease-Free Survival; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015996:Survival Rate
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases