BACKGROUND: Both everolimus and temozolomide are associated with single-agent activity in patients with pancreatic neuroendocrine tumor (NET). A phase 1/2 study was performed to evaluate the safety and efficacy of temozolomide in combination with everolimus in patients who have advanced pancreatic NET. METHODS: Patients were treated with temozolomide at a dose of 150 mg/m(2) per day on days 1 through 7 and days 15 through 21 in combination with everolimus daily in each 28-day cycle. In cohort 1, temozolomide was administered together with everolimus at 5 mg daily. Following demonstration of safety in this cohort, subsequent patients in cohort 2 were treated with temozolomide plus everolimus at 10 mg daily. The duration of temozolomide treatment was limited to 6 months. Patients were followed for toxicity, radiologic and biochemical response, and survival. RESULTS: A total of 43 patients were enrolled, including 7 in cohort 1 and 36 in cohort 2. Treatment was associated with known toxicities of each drug; no synergistic toxicities were observed. Among 40 evaluable patients, 16 (40%) experienced a partial response. The median progression-free survival duration was 15.4 months. Median overall survival was not reached. CONCLUSIONS: Temozolomide and everolimus can be safely administered together in patients with advanced pancreatic NET, and the combination is associated with encouraging antitumor activity. Future studies evaluating the efficacy of combination therapy compared to treatment with either agent alone are warranted.
BACKGROUND: Both everolimus and temozolomide are associated with single-agent activity in patients with pancreatic neuroendocrine tumor (NET). A phase 1/2 study was performed to evaluate the safety and efficacy of temozolomide in combination with everolimus in patients who have advanced pancreatic NET. METHODS:Patients were treated with temozolomide at a dose of 150 mg/m(2) per day on days 1 through 7 and days 15 through 21 in combination with everolimus daily in each 28-day cycle. In cohort 1, temozolomide was administered together with everolimus at 5 mg daily. Following demonstration of safety in this cohort, subsequent patients in cohort 2 were treated with temozolomide plus everolimus at 10 mg daily. The duration of temozolomide treatment was limited to 6 months. Patients were followed for toxicity, radiologic and biochemical response, and survival. RESULTS: A total of 43 patients were enrolled, including 7 in cohort 1 and 36 in cohort 2. Treatment was associated with known toxicities of each drug; no synergistic toxicities were observed. Among 40 evaluable patients, 16 (40%) experienced a partial response. The median progression-free survival duration was 15.4 months. Median overall survival was not reached. CONCLUSIONS:Temozolomide and everolimus can be safely administered together in patients with advanced pancreatic NET, and the combination is associated with encouraging antitumor activity. Future studies evaluating the efficacy of combination therapy compared to treatment with either agent alone are warranted.
Authors: Jennifer A Chan; Keith Stuart; Craig C Earle; Jeffrey W Clark; Pankaj Bhargava; Rebecca Miksad; Lawrence Blaszkowsky; Peter C Enzinger; Jeffrey A Meyerhardt; Hui Zheng; Charles S Fuchs; Matthew H Kulke Journal: J Clin Oncol Date: 2012-07-09 Impact factor: 44.544
Authors: Matthew H Kulke; Keith Stuart; Peter C Enzinger; David P Ryan; Jeffrey W Clark; Alona Muzikansky; Michele Vincitore; Ann Michelini; Charles S Fuchs Journal: J Clin Oncol Date: 2006-01-20 Impact factor: 44.544
Authors: Eric Raymond; Laetitia Dahan; Jean-Luc Raoul; Yung-Jue Bang; Ivan Borbath; Catherine Lombard-Bohas; Juan Valle; Peter Metrakos; Denis Smith; Aaron Vinik; Jen-Shi Chen; Dieter Hörsch; Pascal Hammel; Bertram Wiedenmann; Eric Van Cutsem; Shem Patyna; Dongrui Ray Lu; Carolyn Blanckmeister; Richard Chao; Philippe Ruszniewski Journal: N Engl J Med Date: 2011-02-10 Impact factor: 91.245
Authors: James C Yao; Manisha H Shah; Tetsuhide Ito; Catherine Lombard Bohas; Edward M Wolin; Eric Van Cutsem; Timothy J Hobday; Takuji Okusaka; Jaume Capdevila; Elisabeth G E de Vries; Paola Tomassetti; Marianne E Pavel; Sakina Hoosen; Tomas Haas; Jeremie Lincy; David Lebwohl; Kjell Öberg Journal: N Engl J Med Date: 2011-02-10 Impact factor: 91.245
Authors: Jonathan R Strosberg; Robert L Fine; Junsung Choi; Aejaz Nasir; Domenico Coppola; Dung-Tsa Chen; James Helm; Larry Kvols Journal: Cancer Date: 2010-09-07 Impact factor: 6.860
Authors: M F Stevens; J A Hickman; S P Langdon; D Chubb; L Vickers; R Stone; G Baig; C Goddard; N W Gibson; J A Slack Journal: Cancer Res Date: 1987-11-15 Impact factor: 12.701
Authors: James C Yao; Alexandria T Phan; David Z Chang; Robert A Wolff; Kenneth Hess; Sanjay Gupta; Carmen Jacobs; Jeannette E Mares; Andrea N Landgraf; Asif Rashid; Funda Meric-Bernstam Journal: J Clin Oncol Date: 2008-09-10 Impact factor: 44.544
Authors: Daniel J Ma; Evanthia Galanis; S Keith Anderson; David Schiff; Timothy J Kaufmann; Patrick J Peller; Caterina Giannini; Paul D Brown; Joon H Uhm; Steven McGraw; Kurt A Jaeckle; Patrick J Flynn; Keith L Ligon; Jan C Buckner; Jann N Sarkaria Journal: Neuro Oncol Date: 2014-12-18 Impact factor: 12.300