A phase I study of imatinib, dacarbazine, and capecitabine in advanced endocrine cancers

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Limited therapeutic options exist for advanced endocrine cancers like adrenocortical carcinoma and medullary thyroid carcinoma.
• Pre-clinical data suggested imatinib may have activity in these tumor types.
• A need exists for novel treatment regimens combining targeted therapy with chemotherapy.

Purpose of the Study:

• To establish a safe and novel treatment regimen combining imatinib with dacarbazine and capecitabine.
• To determine the recommended phase II dose for this combination therapy.
• To evaluate the safety and potential activity of this regimen in endocrine cancers.

Main Methods:

• A Phase I dose-escalation study with a 3+3 design was employed.
• The regimen involved imatinib (days 1-21), dacarbazine (days 1-3), and capecitabine (days 1-14) in 21-day cycles.
• Twenty patients with advanced endocrine cancers were treated.

Main Results:

• The recommended Phase II regimen consists of dacarbazine 250 mg/m², capecitabine 500 mg/m² BID, and imatinib 300 mg daily.
• The most frequent toxicities were edema and fatigue; dose-limiting toxicities included fatigue and dyspnea.
• Partial and minor responses were observed in adrenocortical carcinoma patients, with progression-free survival of 8.8 and 6.4 months.

Conclusions:

• The combination of imatinib, dacarbazine, and capecitabine is well-tolerated in patients with advanced endocrine cancers.
• This regimen demonstrated potential activity in adrenocortical carcinoma.
• Further investigation of this combination therapy is warranted for endocrine cancers with limited treatment options.