TY - JOUR
T1 - A phase i study of imexon plus gemcitabine as first-line therapy for advanced pancreatic cancer
AU - Cohen, Steven J.
AU - Zalupski, Mark M.
AU - Modiano, Manuel R.
AU - Conkling, Paul
AU - Patt, Yehuda Z.
AU - Davis, Peg
AU - Dorr, Robert T.
AU - Boytim, Michelle L.
AU - Hersh, Evan M.
PY - 2010/7
Y1 - 2010/7
N2 - Purpose: Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer. Methods: Patients with untreated locally advanced or metastatic pancreatic adenocarcinoma received therapy in sequential cohorts on regimen A (n = 19; imexon 200 or 280 mg/m2 intravenously (IV) over 30 min days 1-5, 15- 19 and gemcitabine 800 or 1,000 mg/m2 IV over 30 min on days 1,8,15 every 28 days) or regimen B (n = 86; imexon 280-1,300 mg/m2 IV over 30-60 min days 1, 8, and 15 and gemcitabine 1,000 mg/m2 IV over 30 min on days 1, 8, and 15 every 28 days). Results: One hundred five patients received 340 treatment cycles (median 2, range 1-16). Patient characteristics: median age 63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and pain, often with transient, acute diarrhea. Best response was confirmed partial response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There was a dose proportional increase in imexon AUC across the doses tested with terminal half life 69 min at the MTD and no alteration of gemcitabine pharmacokinetics. Conclusions: The recommended phase II dose of imexon is 875 mg/m2 with gemcitabine 1,000 mg/m2. DLT was acute abdominal pain and cramping. Encouraging antitumor responses support further evaluation of this combination in advanced pancreatic cancer.
AB - Purpose: Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer. Methods: Patients with untreated locally advanced or metastatic pancreatic adenocarcinoma received therapy in sequential cohorts on regimen A (n = 19; imexon 200 or 280 mg/m2 intravenously (IV) over 30 min days 1-5, 15- 19 and gemcitabine 800 or 1,000 mg/m2 IV over 30 min on days 1,8,15 every 28 days) or regimen B (n = 86; imexon 280-1,300 mg/m2 IV over 30-60 min days 1, 8, and 15 and gemcitabine 1,000 mg/m2 IV over 30 min on days 1, 8, and 15 every 28 days). Results: One hundred five patients received 340 treatment cycles (median 2, range 1-16). Patient characteristics: median age 63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and pain, often with transient, acute diarrhea. Best response was confirmed partial response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There was a dose proportional increase in imexon AUC across the doses tested with terminal half life 69 min at the MTD and no alteration of gemcitabine pharmacokinetics. Conclusions: The recommended phase II dose of imexon is 875 mg/m2 with gemcitabine 1,000 mg/m2. DLT was acute abdominal pain and cramping. Encouraging antitumor responses support further evaluation of this combination in advanced pancreatic cancer.
KW - Gemcitabine
KW - Imexon
KW - Pancreatic cancer
KW - Phase I clinical trial
UR - https://www.scopus.com/pages/publications/77953073888
UR - https://www.scopus.com/pages/publications/77953073888#tab=citedBy
U2 - 10.1007/s00280-009-1162-y
DO - 10.1007/s00280-009-1162-y
M3 - Article
C2 - 19855966
AN - SCOPUS:77953073888
SN - 0344-5704
VL - 66
SP - 287
EP - 294
JO - Cancer Chemotherapy And Pharmacology
JF - Cancer Chemotherapy And Pharmacology
IS - 2
ER -