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.
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Authors | Nancy E Kemeny, Joanne F Chou, Marinela Capanu, Walid K Chatila, Hongyu Shi, Francisco Sanchez-Vega, Thomas Peter Kingham, Louise Catherine Connell, William R Jarnagin, Michael I D'Angelica |
Journal | Annals of surgery
(Ann Surg)
Vol. 274
Issue 2
Pg. 248-254
(08 01 2021)
ISSN: 1528-1140 [Electronic] United States |
PMID | 33938493
(Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. |
Chemical References |
- Floxuridine
- Panitumumab
- Proto-Oncogene Proteins p21(ras)
- Leucovorin
- Fluorouracil
- Camptothecin
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Camptothecin
(analogs & derivatives, therapeutic use)
- Chemotherapy, Adjuvant
- Colorectal Neoplasms
(drug therapy, surgery)
- Female
- Floxuridine
(administration & dosage)
- Fluorouracil
(therapeutic use)
- Humans
- Infusions, Intra-Arterial
- Leucovorin
(therapeutic use)
- Male
- Middle Aged
- Panitumumab
(administration & dosage)
- Proto-Oncogene Proteins p21(ras)
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