Abstract | BACKGROUND:
Imexon is a cyanoaziridine-derived iminopyrrolidone which has synergistic cytotoxicity with gemcitabine. A phase 1 study of the combination demonstrated good tolerance with encouraging clinical activity and thus we conducted this randomized phase II study. MATERIALS AND METHODS: Patients with measurable, metastatic, treatment-naive pancreatic adenocarcinoma were randomized 1:1 to receive gemcitabine at 1000 mg/m days 1, 8, and 15 with either imexon, 875 mg/m or placebo days 1, 8, and 15 every 28 days. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and response rate. RESULTS: A total of 142 patients were randomized, 72 to the imexon containing arm and 70 to the placebo arm. Patients in the imexon arm received an average of 3.6 cycles (range, 1 to 23) compared with 4.4 (range, 1 to 21) in the placebo arm. There was no increased rate of ≥grade 3 toxicity in the imexon arm. Seven patients had objective responses in the imexon arm (13.7%), whereas 9 did in the placebo arm (17%). In the imexon arm, 23 patients had ≥50% reduction in CA 19-9 from baseline (33%), whereas 22 did in the placebo arm (31.4%). The median progression-free survival was 2.8 months in the imexon arm (95% confidence interval [CI], 2.0-4.1 m) and 3.8 months in the placebo arm (95% CI, 2.2-4.7 m), P=0.504. The median overall survival time in the imexon arm was 5.2 months (95% CI, 4.2-6.7 m) as compared with 6.8 m (95% CI, 4.9-8.5 m) in the placebo arm, P=0.6822. CONCLUSIONS:
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Authors | Steven J Cohen, Mark M Zalupski, Paul Conkling, Francis Nugent, Wen Wee Ma, Manuel Modiano, Rolan Pascual, Fa Chyi Lee, Lucas Wong, Evan Hersh |
Journal | American journal of clinical oncology
(Am J Clin Oncol)
Vol. 41
Issue 3
Pg. 230-235
(03 2018)
ISSN: 1537-453X [Electronic] United States |
PMID | 26709865
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
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Chemical References |
- Hexanones
- Deoxycytidine
- 4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one
- Gemcitabine
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Topics |
- Adenocarcinoma
(drug therapy, mortality)
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Deoxycytidine
(administration & dosage, analogs & derivatives)
- Double-Blind Method
- Female
- Hexanones
(administration & dosage)
- Humans
- Male
- Middle Aged
- Pancreatic Neoplasms
(drug therapy, mortality)
- Progression-Free Survival
- Gemcitabine
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