Ramesh K Ramanathan1,2, Shannon L McDonough3, Hagen F Kennecke4, Syma Iqbal5, Joaquina C Baranda6, Tara E Seery7, Howard J Lim4, Aram F Hezel8, Gina M Vaccaro9, Charles D Blanke4,9. 1. Arizona Cancer Center, University of Arizona, Tucson, Arizona. 2. Virginia G. Piper Cancer Center, Scottsdale Healthcare, Scottsdale, Arizona. 3. Southwest Oncology Group Statistical Center, Seattle, Washington. 4. British Columbia Cancer Agency, Vancouver Centre, Vancouver, Canada. 5. USC Norris Comprehensive Cancer Center, Los Angeles, California. 6. University of Kansas Cancer Center, Westwood, Kansas. 7. Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, California. 8. James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York. 9. Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
Abstract
BACKGROUND: The AKT inhibitor MK-2206 at a dose of 60 mg every other day was evaluated in gastric/gastroesophageal junction cancers. METHODS: Patients who had progressed after first-line treatment were eligible. Pertinent eligibility criteria included adequate organ function, a fasting serum glucose level ≤ 150 mg/dL, and less than grade 2 malabsorption or chronic diarrhea. MK-2206 was given orally (60 evaluable patients required). The primary endpoint was overall survival, and a median survival of 6.5 months (power, 89%; significance level, 0.07) was considered encouraging for further investigation. RESULTS: Seventy patients were included in the final analyses. The median age was 59.8 years (range, 30.4-86.7 years); 70% were male, 89% were white, and 7% were Asian. There were 2 deaths possibly related to the study drug (cardiac arrest and respiratory failure). Grade 4 adverse events included hyperglycemia, anemia, and lung infection (1 each). Grade 3 adverse events occurred in < 5% of patients except for fatigue (6%). Other adverse events (all grades) included anemia (17%), anorexia (30%), diarrhea (26%), fatigue (50%), hyperglycemia (30%), nausea (40%), vomiting (22%), dry skin (19%), maculopapular rash (30%), and acneiform rash (13%). The response rate was 1%, the median progression-free survival was 1.8 months (95% confidence interval, 1.7-1.8 months), and the median overall survival was 5.1 months (95% confidence interval, 3.7-9.4 months) CONCLUSIONS: MK-2206 as second-line therapy was well tolerated by an unselected group of patients with gastric/gastroesophageal junction cancers, but it did not have sufficient activity (response rate, 1%; overall survival, 5.1 months) to warrant further testing in this population.
BACKGROUND: The AKT inhibitor MK-2206 at a dose of 60 mg every other day was evaluated in gastric/gastroesophageal junction cancers. METHODS:Patients who had progressed after first-line treatment were eligible. Pertinent eligibility criteria included adequate organ function, a fasting serum glucose level ≤ 150 mg/dL, and less than grade 2 malabsorption or chronic diarrhea. MK-2206 was given orally (60 evaluable patients required). The primary endpoint was overall survival, and a median survival of 6.5 months (power, 89%; significance level, 0.07) was considered encouraging for further investigation. RESULTS: Seventy patients were included in the final analyses. The median age was 59.8 years (range, 30.4-86.7 years); 70% were male, 89% were white, and 7% were Asian. There were 2 deaths possibly related to the study drug (cardiac arrest and respiratory failure). Grade 4 adverse events included hyperglycemia, anemia, and lung infection (1 each). Grade 3 adverse events occurred in < 5% of patients except for fatigue (6%). Other adverse events (all grades) included anemia (17%), anorexia (30%), diarrhea (26%), fatigue (50%), hyperglycemia (30%), nausea (40%), vomiting (22%), dry skin (19%), maculopapular rash (30%), and acneiform rash (13%). The response rate was 1%, the median progression-free survival was 1.8 months (95% confidence interval, 1.7-1.8 months), and the median overall survival was 5.1 months (95% confidence interval, 3.7-9.4 months) CONCLUSIONS:MK-2206 as second-line therapy was well tolerated by an unselected group of patients with gastric/gastroesophageal junction cancers, but it did not have sufficient activity (response rate, 1%; overall survival, 5.1 months) to warrant further testing in this population.
Authors: Young Hwa Soung; Jong Woo Lee; Suk Woo Nam; Jung Young Lee; Nam Jin Yoo; Sug Hyung Lee Journal: Oncology Date: 2006-10-16 Impact factor: 2.935
Authors: Anna Dorothea Wagner; Susanne Unverzagt; Wilfried Grothe; Gerhard Kleber; Axel Grothey; Johannes Haerting; Wolfgang E Fleig Journal: Cochrane Database Syst Rev Date: 2010-03-17
Authors: David Cunningham; Naureen Starling; Sheela Rao; Timothy Iveson; Marianne Nicolson; Fareeda Coxon; Gary Middleton; Francis Daniel; Jacqueline Oates; Andrew Richard Norman Journal: N Engl J Med Date: 2008-01-03 Impact factor: 91.245
Authors: Jaffer A Ajani; Vladimir M Moiseyenko; Sergei Tjulandin; Alejandro Majlis; Manuel Constenla; Corrado Boni; Adriano Rodrigues; Miguel Fodor; Yee Chao; Edouard Voznyi; Cindy Marabotti; Eric Van Cutsem Journal: J Clin Oncol Date: 2007-08-01 Impact factor: 44.544
Authors: S Chia; S Gandhi; A A Joy; S Edwards; M Gorr; S Hopkins; J Kondejewski; J P Ayoub; N Califaretti; D Rayson; S F Dent Journal: Curr Oncol Date: 2015-02 Impact factor: 3.677