Goetz von Wichert

Combination of antiangiogenic therapy using the mTOR-inhibitor everolimus and low-dose chemotherapy for locally advanced and/or metastatic pancreatic cancer: a dose-finding study.

Pancreatic adenocarcinomas are associated with a poor survival prognosis. Besides curative surgical resection, only limited therapies with modest impact are available. New evidence suggests that the mammalian target of rapamycin pathway may be involved in the pathogenesis of neuroendocrine tumors, and breast and renal cell cancer. The phase I study described here was therefore designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of escalating doses of the mammalian target of rapamycin inhibitor everolimus in combination with gemcitabine in patients with advanced pancreatic cancer. Eligible patients had histologically confirmed locally advanced and/or metastatic pancreatic carcinoma and were administered 5 mg everolimus every second day (cohort 1, 2, 3) or 5 mg daily (cohort 4, 5) in combination with escalating low-dose gemcitabine. It was found that if two patients showed DLTs, MTD was reached and gemcitabine dose escalation was stopped at this level. Twenty-seven patients were enrolled in the study (cohort 1: n=3; cohort 2: n=4; cohort 3: n=6; cohort 4: n=7; cohort 5: n=7) and received a maximum 600 mg gemcitabine/week. In cohort 5, two of the six patients experienced DLTs (grade 3 liver toxicity lasting for>7 days). MTD was measured as 400 mg/m2/week gemcitabine plus 5 mg/day everolimus. The MTD of a low-dose gemcitabine treatment in combination with everolimus was determined and no new safety concerns were identified in patients with advanced pancreatic cancer.

Response to Reintroduction of Cetuximab in 5 Patients with Advanced, Chemotherapy-Resistant, Colorectal Cancer without Progressive Disease following First-Line Therapy with a Cetuximab-Containing Regimen

Objective: We aimed to determine the response to cetuximab in advanced, chemotherapy-resistant, colorectal cancer following successful first-line therapy with the antibody. Methods: Five patients with metastatic colorectal cancer were treated with a cetuximab-containing regimen after failure of several conventional chemotherapies. Results: These patients had been successfully treated with cetuximab as first-line therapy, and the antibody was then discontinued without disease progression. No severe toxicities were observed upon reexposure to cetuximab. Partial response was noted in 1 patient and tumor stabilization in 2 patients. Conclusion: Reintroduction of cetuximab in combination with chemotherapy is safe and efficacious in patients with colorectal cancer whose tumors were not refractory to a prior cetuximab-containing therapy.