Abstract | BACKGROUND: METHODS: Twenty-six patients, PS 0-1, with class II hepatic metastases received chemotherapy combining irinotecan 260 mg/m(2) on day 1 for UGT1A1 6/6 and 6/7 genotypes and 220 mg/m(2) for UGT1A1 7/7 genotypes, with leucovorin on day 1, 5FU 400 mg/m(2) bolus on day 1 and continuous 5FU infusion for 46 h, and cetuximab on day 1 (day 1 = day 14). Primary prevention with lenograstim (day 5-9) was given to UGT1A1 6/7 and 7/7 genotypes. The primary endpoint was the response rate (RECIST1.1), and the secondary endpoints were tolerance (NCI-CTC criteria) and R0 resection rate. RESULTS: The average number of cycles per patient was 6 (±1.9). The UGT1A1 genotype was 6/6 in 34.6 %, 6/7 in 53.9 %, and 7/7 in 11.5 % of patients. At 6 cycles, 18 patients (69.2 %) presented a partial response, 5 patients (19.2 %) had stable disease, 2 patients (7.7 %) died independently of chemotherapy, and 1 patient (3.9 %) refused the treatment after 3 cycles. Four patients received 2 more cycles and the cumulative response rate at 8 cycles was 76.9 % (20/26). There was no progression. Among assessable patients (n = 23), the overall response rate was 82.6 % and 21 patients (80.7 %) had a metastasis resection. The most frequent grade 3-4 toxicities were neutropenia (31 %), diarrhea (20.8 %), and anorexia (16.4 %). There were no deaths due to toxicity. CONCLUSIONS: High-dose FOLFIRI combined with cetuximab yielded high response rates and enabled complete resection of class II hepatic metastases in most patients. It seemed to be well-tolerated among healthy selected patients thanks to irinotecan dose adaptation according to UGT1A1 pharmacogenomics status. This intensified chemotherapy regimen needs to be confirmed in a randomized, phase III study.
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Authors | Jean Marc Phelip, Laurent Mineur, Christelle De la Fouchardière, Etienne Chatelut, Jean Louis Quesada, Xavier Roblin, Denis Pezet, Christophe Mendoza, Emmanuel Buc, Michel Rivoire |
Journal | Annals of surgical oncology
(Ann Surg Oncol)
Vol. 23
Issue 7
Pg. 2161-6
(07 2016)
ISSN: 1534-4681 [Electronic] United States |
PMID | 26739304
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
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Chemical References |
- Irinotecan
- UGT1A1 enzyme
- Glucuronosyltransferase
- Cetuximab
- Leucovorin
- Fluorouracil
- Camptothecin
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Camptothecin
(administration & dosage, analogs & derivatives)
- Cetuximab
(administration & dosage)
- Colorectal Neoplasms
(drug therapy, genetics, pathology, surgery)
- Combined Modality Therapy
- Female
- Fluorouracil
(administration & dosage)
- Follow-Up Studies
- Glucuronosyltransferase
(genetics)
- Humans
- Irinotecan
- Leucovorin
(administration & dosage)
- Liver Neoplasms
(drug therapy, genetics, secondary, surgery)
- Male
- Middle Aged
- Prognosis
- Survival Rate
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