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Nelfinavir added to chemotherapy shows promise for pancreatic cancer

Last Updated: 2008-06-24 16:03:03 -0400 (Reuters Health)

NEW YORK (Reuters Health) - A combination of the protease inhibitor nelfinavir and a conventional chemotherapy regimen of gemcitabine and cisplatin plus radiotherapy has "acceptable toxicity and promising activity" in patients with locally advanced pancreatic cancer, European investigators say.

In a study published in the June 1 issue of the Journal of Clinical Oncology, Dr. Thomas B. Brunner of the University of Oxford, UK, and colleagues initiated oral nelfinavir, 1,250 mg twice daily, three days prior to and throughout chemo- and radiotherapy.

Twelve patients participated in the study. In addition to nelfinavir, chemotherapy consisted of gemcitabine (200 mg/m² in 6 patients, and 300 mg/m² in the other 6 patients) on days 1, 8, 22, and 29, with cisplatin, 30 mg/m², administered on the same days. Radiotherapy consisted of a booster dose of 59.4 Gy followed by 50.4 Gy daily.

Nelfinavir-induced phospho-Akt downregulation was monitored by immunoblotting in patient leukocytes. Response was assessed with positron emission tomography (PET), computed tomography (CT) and CA19-9 levels. After treatment, the investigators resected the tumors and studied the tissue.

At each gemcitabine dose, five of six patients completed chemoradiotherapy. Two patients had incomplete chemoradiotherapy because of clinical depression or peritoneal metastasis.

Grade 4 toxicities occurred with the higher dose and consisted of a transaminase elevation as a result of biliary stent occlusion and acute cholecystitis as a result of peritoneal metastasis. Grade 3 nausea and vomiting occurred in one patient, and severe weight loss occurred in one patient.

Partial responses were observed on CT in five of ten patients who completed chemoradiotherapy. Of nine patients assessable by PET, 5 had complete responses, 2 had partial responses, and 2 had unchanged disease. In 6 of the 10 patients who completed chemoradiotherapy, complete resection was possible.

"This report demonstrates that the use of nelfinavir with chemoradiotherapy is safe in locally advanced pancreatic ductal adenocarcinoma because no added toxicity was observed," Dr. Brunner and colleagues write.

The investigators report that a phase II study in pancreatic ductal adenocarcinoma is being designed.

J Clin Oncol 2008;26:2699-2706.

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