Trial Information

Phase I Study of Low-Dose Fractionated Radiotherapy as a Chemosensitizer for Gemcitabine and Erlotinib in Patients With Locally Advanced or Limited Metastatic Pancreatic Cancer

Pancreatic cancer is nearly universally fatal, with approximately 38,000 new cases and
34,000 deaths expected in 2008.1 The majority of patients present with disease that is not
amenable to curative resection. For patients with metastatic disease, one standard
treatment is the combination of gemcitabine with the small molecule epidermal growth factor
tyrosine kinase inhibitor erlotinib. This combination results in a modest survival benefit
compared to single agent gemcitabine.2

For patients presenting with localized but unresectable disease, the standard treatment
remains controversial. Early studies demonstrated that chemotherapy and radiation was
superior to either modality alone.3 However, recent studies of systemic therapy alone have
typically included a small but real minority of patients with locally advanced disease,
supporting that systemic therapy alone is a reasonable treatment option.2 Adding to the
confusion are recent European reports that systemic therapy alone may be superior to
combined modality therapy, at least when used initially.4 The greatest benefit of external
beam radiotherapy may be after a period of full-dose chemotherapy alone, to ensure that
rapid metastases do not develop.5 A limitation of beginning treatment with conventional
external beam radiotherapy is a requirement to reduce dosing of gemcitabine by 40-50%.
Given the safety and preclinical rationale for LDRT, we propose this phase I study to
evaluate the safety of LDRT with standard dosing of gemcitabine and erlotinib in patients
with locally advanced or limited metastatic pancreatic cancer. Patients will be enrolled in
cohorts with escalating doses of low dose radiotherapy. Radiation ports will be uniform
between patients as described in Section 5.6 below. As LDRT is administered to sites of
disease in liver and abdominal cavity to iliac crest, patients with metastatic disease
confined to these areas will be eligible. For patients with locally advanced disease, this
protocol also has high rationale, as the overwhelming majority of patients develop and
succumb to recurrences in liver and abdominal cavity,10 areas which would be covered by the
proposed radiation field. The dose of 2880 cGy is the limit because of kidney and other
upper abdominal organ potential for toxicity.