J Korean Med Sci.  2013 Aug;28(8):1248-1252. 10.3346/jkms.2013.28.8.1248.

Imatinib Plasma Monitoring-Guided Dose Modification for Managing Imatinib-Related Toxicities in Gastrointestinal Stromal Tumor Patients

• Yoon S
• Ryu MH
• Yoo C
• Beck MY
• Ryoo BY
• Kang YK

• KMID: 1793034
• DOI: http://doi.org/10.3346/jkms.2013.28.8.1248

Abstract

Imatinib, the first-line treatment in patients with advanced gastrointestinal stromal tumors (GIST), is generally well tolerated, although some patients have difficulty tolerating the standard dose of 400 mg/day. Adjusting imatinib dosage by plasma level monitoring may facilitate management of patients who experience intolerable toxicities due to overexposure to the drug. We present two cases of advanced GIST patients in whom we managed imatinib-related toxicities through dose modifications guided by imatinib plasma level monitoring. Imatinib blood level testing may be a promising approach for fine-tuning imatinib dosage for better tolerability and optimal clinical outcomes in patients with advanced GIST.

Keyword

Gastrointestinal Stromal Tumors (GIST); Imatinib; Imatinib Plasma Monitoring; Dose-Modification

MeSH Terms

Aged
Antineoplastic Agents/blood/*therapeutic use
Benzamides/blood/*therapeutic use
Drug Monitoring
Exons
Gastrointestinal Neoplasms/*drug therapy/pathology/radiography
Gastrointestinal Stromal Tumors/*drug therapy/pathology/radiography
Humans
Liver Neoplasms/secondary
Male
Mutation
Piperazines/blood/*therapeutic use
Positron-Emission Tomography
Proto-Oncogene Proteins c-kit/genetics
Pyrimidines/blood/*therapeutic use
Tomography, X-Ray Computed
Antineoplastic Agents
Benzamides
Piperazines
Proto-Oncogene Proteins c-kit
Pyrimidines

Figure

• 

  Fig. 1 Imatinib plasma monitoring-guided dose modification reduced toxicities and maintained response in patient 1. A patient with resected small bowel GIST and multiple liver metastases responded to imatinib treatment, as PET/CT scans show a significant decrease in maximum standardized uptake value from 4.2 to 2.9 in one of his liver metastases one month after he restarted imatinib (A; arrow heads). However, the patient had grade 3 dyspnea and grade 2 ascites (C). Serial measurements of imatinib plasma concentration guided imatinib dose modification from 400 mg/day to 300 mg/day and then to 200 mg/day; his liver metastases remained stable (B) and his fluid retention, including dyspnea and ascites, was greatly improved (C). Imatinib dose was increased to 300 mg/day upon patient request; he tolerated ascites and dyspnea (C) and his disease was stable (B). D, day; IM, imatinib; M, month; SD, stable disease.

• 

  Fig. 2 Imatinib plasma monitoring.guided dose modification reduced toxicities and maintained response in patient 2. A patient with resected duodenal GIST and a liver metastasis responded to imatinib treatment with a partial response (A; arrows). However, at the standard dose of 400 mg/day, the patient had grade 3 dyspnea and grade 2 pericardial effusion (B). Serial measurements of imatinib plasma concentration guided imatinib dose modification from 400 mg/day to 300 mg/day, 200 mg/day and then to 100 mg/day; his fluid retention (dyspnea and pericardial effusion) was improved (B), with partial response maintained in his liver metastases (A). D, day; IM, imatinib; M, month; PR, partial response; Y, year.

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