A phase 2 study of adjuvant chemotherapy with 5-fluorouracil/leucovorin and oxaliplatin after lung metastasectomy for colorectal cancer (WJOG5810G)

Abstract

Background

The clinical significance of adjuvant chemotherapy after lung metastasectomy for colorectal cancer remains unknown. This phase 2 study evaluated adjuvant chemotherapy with modified 5-fluorouracil/leucovorin and oxaliplatin (mFOLFOX6) after lung metastasectomy.

Methods

Eligibility criteria included colorectal adenocarcinoma, first curative resection of ≤4 lung metastases, and no prior chemotherapy. Treatment consisted of 12 cycles of mFOLFOX6. The primary endpoint was the 5-year overall survival (OS) rate, with the expectation of 50% (threshold, 35%) and a planned sample size of 100 (90% power; alpha error, 5%).

Results

Fifty-two patients were enrolled between July 2011 and July 2014; patient enrollment was closed prematurely because of slow accrual. Excluding four ineligible patients, the characteristics of the 48 patients in the efficacy analysis set were a median age of 62 years (range, 43–75 years), Eastern Cooperative Oncology Group performance status of 0 in 45 patients, prior resection of extrathoracic metastasis in four patients, and postoperative carcinoembryonic antigen within normal range in 43 patients; the status of lung metastasis was single in 34 patients, unilateral in 40 patients, and metachronous in 41 patients; and a disease-free interval between primary tumor resection and diagnosis of lung metastasis of <2 years in 33 patients. The 5-year OS rate was 85.2% (95% confidence interval [CI], 71.4%–92.6%), and the 5-year disease-free survival rate was 60.2% (95% CI, 44.9%–72.4%). Forty-one of the 52 patients (78.8%) in the safety analysis set completed 12 cycles of mFOLFOX6. Grade ≥3 adverse events were neutropenia (50.0%), fatigue (7.7%), peripheral sensory neuropathy (7.7%), and other (<5%).

Conclusions

Adjuvant chemotherapy with mFOLFOX6 is feasible, and may be effective after lung metastasectomy for colorectal cancer.