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Imatinib Mesylate in Patients With Adenoid Cystic Cancers of the Salivary Glands Expressing c-kit: A Princess Margaret Hospital Phase II Consortium Study

From the Princess Margaret Hospital Phase II Consortium; The University of Chicago Phase II Consortium; and Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD

Address reprint requests to Sebastien J. Hotte, MD, Juravinski Cancer Centre at Hamilton Health Sciences, 699 Concession St, Hamilton, Ontario, Canada, L8V 5C2; e-mail: sebastien.hotte{at}hrcc.on.ca

PURPOSE: This study aimed to assess the antitumor activity of imatinib in adenoid cystic carcinoma (ACC) of the salivary gland expressing c-kit. A high level of c-kit expression has been identified in more than 90% of ACCs. Imatinib specifically inhibits autophosphorylation of the bcr-abl, platelet-derived growth factor receptor beta, and c-kit tyrosine kinases.

PATIENTS AND METHODS: In a single-arm, two-stage, phase II clinical trial, adult patients with unresectable or metastatic ACC measurable by Response Evaluation Criteria in Solid Tumors Group criteria and expressing c-kit by immunohistochemistry were treated with imatinib 400 mg orally bid. Response was assessed every 8 weeks.

RESULTS: Sixteen patients have been enrolled onto the study; 10 were female. Median age was 47 years (range, 31 to 69 years). Median Eastern Cooperative Oncology Group performance status was 1 (range, 0 to 2). Fourteen patients had lung metastases, 14 had prior radiotherapy, and six had prior chemotherapy. Toxicities occurring in at least 50% of patients included fatigue, nausea, vomiting, diarrhea, anorexia, edema, dyspnea, and/or headache, usually of mild to moderate severity. In 15 patients assessable for response, no objective responses have been observed. Nine patients had stable disease as best response. Six patients had progressive disease after two cycles.

CONCLUSION: Because of the lack of activity, the study has been stopped after the first stage and additional evaluation of imatinib in this population is not warranted. Overexpression of wild-type c-kit was not sufficient for clinical benefit from imatinib in ACC. Accrual to this study was rapid for a relatively rare cancer, encouraging additional efforts to identify more effective systemic therapy for these patients.

Supported by clinical trial contracts from the US National Cancer Institute, N01-CM-17107-01 and N01-CM-17102-01.

Presented in part at the European Conference on Clinical Oncology (ECCO) meeting, Copenhagen, Denmark, September 21-25, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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