Gene interactions and pathways from curated databases and text-mining
J Clin Oncol 2009, PMID: 19047305

Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer.

Wolpin, Brian M; Hezel, Aram F; Abrams, Thomas; Blaszkowsky, Lawrence S; Meyerhardt, Jeffrey A; Chan, Jennifer A; Enzinger, Peter C; Allen, Brittany; Clark, Jeffrey W; Ryan, David P; Fuchs, Charles S

OBJECTIVE

The PI3K/Akt/mTOR pathway is activated in the majority of pancreatic cancers, and inhibition of this pathway has antitumor effects in preclinical studies. We performed a multi-institutional, single-arm, phase II study of RAD001(everolimus), an oral inhibitor of mTOR, in patients who experienced treatment failure on first-line therapy with gemcitabine.

METHODS

Thirty-three patients with gemcitabine-refractory, metastatic pancreatic cancer were treated continuously with RAD001 at 10 mg daily. Prior treatment with fluorouracil in the perioperative setting was allowed. Patients were observed for toxicity, treatment response, and survival.

RESULTS

Treatment with single-agent RAD001 was well-tolerated; the most common adverse events were mild hyperglycemia and thrombocytopenia. No patients were removed from the study because of drug-related adverse events. No complete or partial treatment responses were noted, and only seven patients (21%) had stable disease at the first restaging scans performed at 2 months. Median progression-free survival and overall survival were 1.8 months and 4.5 months, respectively. One patient (3%) had a biochemical response, defined as > or = 50% reduction in serum CA19-9.

CONCLUSIONS

Although well-tolerated, RAD001 administered as a single-agent had minimal clinical activity in patients with gemcitabine-refractory, metastatic pancreatic cancer. Future studies in metastatic pancreatic cancer should assess the combination of mTOR inhibitors with other agents and/or examine inhibitors of other components of the PI3K/Akt/mTOR pathway.

Diseases/Pathways annotated by Medline MESH: Pancreatic Neoplasms
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Text Mining Data

mTOR ⊣ RAD001: " We performed a multi-institutional, single-arm, phase II study of RAD001 ( everolimus ), an oral inhibitor of mTOR , in patients who experienced treatment failure on first-line therapy with gemcitabine "

Manually curated Databases

No curated data.