Multicenter phase II study of modified FOLFOX6 as neoadjuvant chemotherapy for patients with unresectable liver-only metastases from colorectal cancer in Japan: ROOF study

• Published in: International journal of clinical oncology Vol. 18; no. 2; pp. 335 - 342
• Main Authors: Takahashi, Takao, Shibata, Yoshihisa, Tojima, Yuichiro, Tsuboi, Kenji, Sakamoto, Eiji, Kunieda, Katsuyuki, Matsuoka, Hiroshi, Suzumura, Kazuyoshi, Sato, Mikinori, Naganuma, Tatsushi, Sakamoto, Junichi, Morita, Satoshi, Kondo, Ken
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.04.2013; Springer Nature B.V
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Cancer Research; Chemotherapy; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Colorectal Neoplasms - surgery; Combined Modality Therapy; Drug-Related Side Effects and Adverse Reactions - chemically induced; Drug-Related Side Effects and Adverse Reactions - pathology; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Humans; Japan; Leucovorin - administration & dosage; Leucovorin - adverse effects; Liver; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Liver Neoplasms - secondary; Liver Neoplasms - surgery; Male; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Neoadjuvant Therapy - adverse effects; Oncology; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; Original Article; Surgery; Surgical Oncology; Survival Rate; Japan; Unresectable liver-only metastases; Liver resection; ROOF study; mFOLFOX6; Colorectal cancer
• ISSN: 1341-9625; 1437-7772
• DOI: 10.1007/s10147-012-0382-z

Background Neoadjuvant chemotherapy for unresectable colorectal liver metastases can reduce tumor size, which sometimes leads to curative resection. The aim of the present study was to identify and describe patients with initially unresectable liver-only metastases from colorectal cancer who obtained sufficient chemotherapeutic benefit that eventually lead to the removal of the metastatic diseases in the liver. Methods A phase II multicenter cooperative study was conducted in 38 medical institutions using modified FOLFOX6 (mFOLFOX6) as neoadjuvant chemotherapy from January 2008 to June 2009. Patients with liver-only metastases from colorectal cancer that was deemed not optimally resectable by liver surgeons received mFOLFOX6 as preoperative neoadjuvant chemotherapy for 6-8 cycles. Patients were reassessed for resectability after 6 cycles of mFOLFOX6. Surgery was carried out 3-6 weeks after chemotherapy. The primary endpoint was the rate of macroscopic curative surgery including liver resection. Results 36 patients (23 male/13 female, ECOG performance status 0-1) were enrolled. The median age of the patients was 62.5 years; 78% (28 patients) had 5 or more metastatic tumors, and 50% (18 patients) had metastatic tumors over 5 cm diameter. The mFOLFOX6 regimen was safety administered resulting in 18 partial responses (50%), 12 stable disease, and 4 progressive disease. There was no grade 3/4 neurotoxicity. Fourteen patients (38.9%) underwent surgery (R0: 13; R1: 1). Of these, thirteen patients (36.1%) underwent R0 surgery. Conclusions Our data suggest that mFOLFOX6 has a high response rate in patients with liver-only metastases from colorectal cancer, allowing for R0 resection of liver metastases in a proportion of patients initially not judged to be optimally resectable.