A phase 2 study of oral MKC-1, an inhibitor of importin-β, tubulin, and the mTOR pathway in patients with unresectable or metastatic pancreatic cancer
Jason E Faris, Jamie Arnott, Hui Zheng, David P Ryan, Thomas A Abrams, Lawrence S Blaszkowsky, Jeffrey W Clark, Peter C Enzinger, Aram F Hezel, Kimmie Ng, Brian M Wolpin, Eunice L Kwak, Jason E Faris, Jamie Arnott, Hui Zheng, David P Ryan, Thomas A Abrams, Lawrence S Blaszkowsky, Jeffrey W Clark, Peter C Enzinger, Aram F Hezel, Kimmie Ng, Brian M Wolpin, Eunice L Kwak
Abstract
Background: MKC-1 is an orally available cell cycle inhibitor with downstream targets that include tubulin and the importin-β family. We conducted an open-label Phase II study with MKC-1 in patients with advanced pancreatic cancer.
Methods: Eligibility criteria included unresectable or metastatic pancreatic cancer, performance status of 1 or better, and failure of at least one prior regimen of chemotherapy. MKC-1 was administered orally, twice daily, initially at 100 mg/m(2) dosing for 14 consecutive days of a 28-day cycle. This schedule was modified during the trial to fixed and continuous dosing of 150 mg per day.
Results: 20 of an original target of 33 patients were accrued, with a median age of 61 (range 44-81). No objective responses were observed, with one patient demonstrating stable disease. Overall survival was 101 days from the start of MKC-1 administration, and median time to progression was 42 days. The most common adverse events listed as related or possibly related to MKC-1 administration were hematologic toxicities and fatigue. One patient developed grade 5 (fatal) pancytopenia. Grade 3 and 4 events included cytopenias (lymphopenia, anemia), hyperbilirubinemia, pneumonia, mucositis, fatigue, infusion reaction, anorexia, and hypoalbuminemia.
Conclusions: MKC-1 administration was associated with substantial toxicity and did not demonstrate sufficient activity in patients with advanced pancreatic cancer to justify further exploration in this patient population.
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Source: PubMed