A lower dosage of imatinib in patients with gastrointestinal stromal tumors with toxicity of the treatment

Abstract

This study investigated the efficiency and safety of imatinib in the lower dose (300 mg/d) in patients with gastrointestinal stromal tumor (GIST) who cannot tolerate imatinib in the standard dose (400 mg/d).Steady-state imatinib trough concentration (Cmin) values in 18 patients with GIST who were taking 300 mg/d or 400 mg/d imatinib were measured. The clinical features, toxicity data, and follow-up data were collected.Around 18 patients with GIST were investigated in which 9 patients received 300 mg/d imatinib. The mean imatinib Cmin value of the 18 patients was 1841 ng/mL (1018–3897 ng/mL). The difference between the patients treated with 400 mg/d (n=9) and those treated with 300 mg/d (n = 9), which have imatinib Cmin values of 2122±1003 ng/mL and 1559±478 ng/mL, respectively, was not significant (P = 0.148). In total, 12 of the 18 patients had complete resection of the primary tumor, 8 of whom received postoperative imatinib 300 mg/d. After the average follow-up of 15.4 months, no recurrence was documented. Of the 6 patients with unresected GIST, 1 received imatinib 300 mg/d for 13 months. The tumor size of this patient continued to decrease. In contrast to patients treated with imatinib 400 mg/d, patients treated with imatinib 300 mg/d notably exhibited lesser drug-related side effects.Patients with GIST who exhibited intolerance to the standard dose of imatinib (400 mg/d), a lower dose of 300 mg/d could provide not only sufficient plasma Cmin and good disease control but also the alleviation of the side effects.

Chinese consensus guidelines for diagnosis and management of gastrointestinal stromal tumor

“…If possible, it is recommended to monitor the imatinib plasma concentration on the following patients: patients who developed progression under first-line imatinib therapy at 400 mg/d dose; patients with severe drug adverse reactions which are caused by excessive imatinib plasma concentration. It is reasonable to reduce imatinib dose with minimal effective blood concentration; for incompliant patients who did not take regular medication, if the plasma imatinib concentration is lower than 1,100 ng/mL, the clinical efficacy will decrease and the disease will progress rapidly ( 59 , 60 ).…”

Long-term adjuvant imatinib treatment for a patient who underwent complete resection of a localized recurrent gastrointestinal stromal tumor after preoperative imatinib treatment

“…They found that imatinib plasma C min at 300 mg/day was 1559 ± 478 ng/mL, which was comparable to that in patients who were treated with 400 mg/day (C min 2262 ± 1009 ng/mL). [24] In this case, long-term follow-up showed no signs of tumor recurrence. Although the C min value of 1015.7 ng/mL was slightly below the threshold range given above, it might indicate that the imatinib plasma concentration was effective.…”