Nancy E Kemeny1, Joanne F Chou2, Marinela Capanu2, Walid K Chatila3, Hongyu Shi2, Francisco Sanchez-Vega4,5, Thomas Peter Kingham1, Louise Catherine Connell1, William R Jarnagin1, Michael I D'Angelica6. 1. Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. 2. Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. 3. Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY. 4. Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. 5. Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. 6. Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Abstract
OBJECTIVE/ BACKGROUND: The purpose was to determine whether adding Pmab versus no Pmab to an adjuvant regimen of hepatic arterial infusion (HAI) of floxuridine (FUDR) plus systemic (SYS) leucovorin, fluorouracil, and irinotecan (FOLFIRI) improves 15-month recurrence-free survival for patients with RAS wild-type colorectal cancer. Secondary endpoints included overall survival, toxicity, and influence of predictive biomarkers. METHODS: This phase II trial randomized patients with KRAS wild-type resected colorectal liver metastases to adjuvant HAI FUDR + SYS FOLFIRI +/- Pmab (NCT01312857). Patients were stratified by clinical risk score and previous chemotherapy. Based on an exact binomial design, if one arm had ≥24 patients alive and disease-free at 15 months that regimen was considered promising for further investigation. RESULTS: Seventy-five patients were randomized. Patient characteristics and toxicity were not different in the 2 arms, except for rash in +Pmab arm. Grade 3/4 elevation in bilirubin or alkaline phosphatase did not differ in the 2 arms. Twenty-five (69%; 95% CI, 53-82) patients in the Pmab arm versus 18 (47%; 95% CI, 32-63) patients in the arm without Pmab were alive and recurrence-free at 15 months. Only the Pmab arm met the decision rule, while the other arm did not. After median follow-up of 56.6 months, 3-year recurrence-free survival was 57% (95% CI, 43-76) and 42% (95% CI, 29-61), and 3-year overall survival was 97% (95% CI, 90-99) and 91% (95% CI, 83-99), +/- Pmab, respectively. CONCLUSIONS: The addition of Pmab to HAI FUDR + SYS FOLFIRI showed promising activity without increased biliary toxicity and should be further investigated in a larger trial.
OBJECTIVE/ BACKGROUND: The purpose was to determine whether adding Pmab versus no Pmab to an adjuvant regimen of hepatic arterial infusion (HAI) of floxuridine (FUDR) plus systemic (SYS) leucovorin, fluorouracil, and irinotecan (FOLFIRI) improves 15-month recurrence-free survival for patients with RAS wild-type colorectal cancer. Secondary endpoints included overall survival, toxicity, and influence of predictive biomarkers. METHODS: This phase II trial randomized patients with KRAS wild-type resected colorectal liver metastases to adjuvant HAI FUDR + SYS FOLFIRI +/- Pmab (NCT01312857). Patients were stratified by clinical risk score and previous chemotherapy. Based on an exact binomial design, if one arm had ≥24 patients alive and disease-free at 15 months that regimen was considered promising for further investigation. RESULTS: Seventy-five patients were randomized. Patient characteristics and toxicity were not different in the 2 arms, except for rash in +Pmab arm. Grade 3/4 elevation in bilirubin or alkaline phosphatase did not differ in the 2 arms. Twenty-five (69%; 95% CI, 53-82) patients in the Pmab arm versus 18 (47%; 95% CI, 32-63) patients in the arm without Pmab were alive and recurrence-free at 15 months. Only the Pmab arm met the decision rule, while the other arm did not. After median follow-up of 56.6 months, 3-year recurrence-free survival was 57% (95% CI, 43-76) and 42% (95% CI, 29-61), and 3-year overall survival was 97% (95% CI, 90-99) and 91% (95% CI, 83-99), +/- Pmab, respectively. CONCLUSIONS: The addition of Pmab to HAI FUDR + SYS FOLFIRI showed promising activity without increased biliary toxicity and should be further investigated in a larger trial.
Authors: N Kemeny; Y Huang; A M Cohen; W Shi; J A Conti; M F Brennan; J R Bertino; A D Turnbull; D Sullivan; J Stockman; L H Blumgart; Y Fong Journal: N Engl J Med Date: 1999-12-30 Impact factor: 91.245
Authors: Michael G House; Nancy E Kemeny; Mithat Gönen; Yuman Fong; Peter J Allen; Philip B Paty; Ronald P DeMatteo; Leslie H Blumgart; William R Jarnagin; Michael I D'Angelica Journal: Ann Surg Date: 2011-12 Impact factor: 12.969
Authors: John Primrose; Stephen Falk; Meg Finch-Jones; Juan Valle; Derek O'Reilly; Ajith Siriwardena; Joanne Hornbuckle; Mark Peterson; Myrddin Rees; Tim Iveson; Tamas Hickish; Rachel Butler; Louise Stanton; Elizabeth Dixon; Louisa Little; Megan Bowers; Siân Pugh; O James Garden; David Cunningham; Tim Maughan; John Bridgewater Journal: Lancet Oncol Date: 2014-04-07 Impact factor: 41.316