A phase II trial of gefitinib monotherapy in patients with unresectable adrenocortical carcinoma (ACC)

Abstract

15527 Background: ACC is a rare malignancy with a very poor prognosis. Surgery is the only potential curative option. Gefitinib is an oral EGFR inhibitor that may have activity in solid tumors that express EGFR. ACC over expresses EGFR in a high proportion of cases. Methods: From April 2004 through December 2006, the ACC Working Group conducted a phase II trial of Gefitinib as second line, monotherapy in patients with pathologically confirmed unresectable ACC who had progressed on mitotane or chemotherapy. All prior systemic therapy was discontinued 28 days prior to starting gefitinib. Patients were ineligible if: had received prior therapy with any EGFR inhibitor, pregnant or breast feeding, had other co-existing malignancies (other than basal cell carcinoma or cervical cancer in situ), had an ECOG PS > 2, absolute neutrophil counts < 1,500, or platelets < 20,000. Patients were not allowed concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John’s Wort. Patients took gefitinib 250 mg orally once a day. Each cycle was 21 days with radiological assessment every 6 weeks.Response rate as determined by RECIST criteria was the primary endpoint. Results: 19 patients accrued to the study (18 with measurable disease and 1 without). Pt Characteristics: Female 79% (15/19); Median age 48 (range 26–74); 84% (12 female and 4 male =15/19) of the patients had steroid secreting tumors. Grade 3 toxicity was noted in 2 patients and included, hypertension and lower extremity edema and elevated liver transaminases. No grade 4 toxicities occurred. Of 19 patients evaluable, there were no complete responders, partial responders or patients with stable disease (0% response rate; 95% CI: 0%-18%). Conclusions: Gefitinib demonstrated no activity in patients with unresectable ACC. This study is now closed. This study demonstrated the ability to successfully accrue to a trial of novel agents in rare tumors in a multicenter setting. [Table: see text]