Phase II Study of Irinotecan and Panitumumab as Second-Line Therapy for Patients With Advanced Esophageal Adenocarcinoma
Esophageal cancer is a highly lethal malignancy that is increasing in incidence, especially
the histologic subtype of adenocarcinoma. Fully 50% of patients present with advanced,
incurable disease. Of the remainder who are diagnosed at curable stages, at most 30% are
long-term survivors. Advances in therapy for both local and advanced disease have been
stagnant in the past few decades. As such, there is an urgent need for advances in therapy.
The development of modern cytotoxic chemotherapy and in particular, biologically targeted
agents, provides hope for improving the outcome in these patients.
The semi-synthetic derivative of camptothecin, irinotecan, is active in esophageal
adenocarcinoma, both alone and in combination with cisplatin. Use as front-line therapy in
both multi-modality regimens and combination chemotherapy is common. More recently, the
elucidation of the role of the epidermal growth factor receptor (EGFR) pathway in esophageal
cancer has resulted in the pre-clinical and clinical study of the activity of EGFR directed
agents for treatment of esophageal cancer.
The anti-EGFR antibodies, panitumumab and cetuximab, are active as both single agents and in
combination with cytotoxic chemotherapy in patients with colorectal adenocarcinoma. In
particular, the combination of irinotecan and cetuximab is active for irinotecan refractory
colorectal cancer, while panitumumab is active compared with best supportive care. In our
clinic, we have empiric evidence for the unexpectedly significant activity of the
combination of cetuximab and irinotecan as third-line treatment for advanced esophageal
adenocarcinoma. Panitumumab has the clinical advantages, compared with cetuximab, of being
fully human,, thus resulting in a lower frequency of infusion reactions.
This recent experience with these targeted agents in solid tumors, while still promising,
has yielded relatively modest results.7-11 Notably, however, retrospective analyses of
clinical trials are consistently revealing that differences in treatment effect between
subgroups of patients can be associated with specific molecular profiles.12-18 These
findings suggest the potential for a more rational approach to trial design that would use
patient and tumor characteristics to select patients for therapy, thus enriching the
population of responders.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall Best Response Rate
Michael Gibson, MD
University of Pittsburgh
United States: Food and Drug Administration
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|