Ruihua Xu¹, Yuhong Li¹, Huiyan Luo¹, Wei Wang², Zhiqiang Wang¹, Xia Yuan³, Dong Ma⁴, Fenghua Wang¹, Dongshen Zhang¹, Daren Lin⁵, Yinchen Lin⁶, Jun Jia⁷, Xiahua Xu⁸, Jiewen Peng⁹

¹Medical Oncology, Sun Yat-sen University Cancer Center, ²Medical Oncology, The First People's Hospital of Foshan, ³Medical Oncology, Huizhou Central Hospita, ⁴Medical Oncology, Guangdong General Hospital, ⁵Medical Oncology, Jiangmen Central Hospital, ⁶Medical Oncology, Cancer Hospital of Shantou University Medical College, ⁷Medical Oncology, Dongguan People's Hospital, ⁸Medical Oncology, Tumor Hospital of Guangxi Medical University, ⁹Medical Oncology, Zhongshan People's Hospital

Objective:Colorectal cancer (CRC) is one of the most common malignant tumors. Most of advanced CRC will progress after first-line treatment; therefore, seeking an efficient and low toxic maintaining regimen to prolong progression free survival (PFS) becomes a hot topic. Some clinical researches demonstrated that maintaining treatment followed first-line treating could extend PFS. Our previous non-randomized small sample study indicated that patients receiving first-line treatment of XELOX followed by capecitabine as maintaining therapy had significantly prolonged median time to progression (TTP). Therefore, we plan to initiate the first randomized study to evaluate the efficacy and safety of maintenance therapy with capecitabine following induction of (XELOX) or (FOLFOX) versus observation until progression in first-line therapy in metastatic CRC. Method: This is a multi-center, randomized phase III study. Patients who received 18-24 weeks chemotherapy with XELOX or FOLFOX and achieved objective response or stable disease were randomized 1:1 to received maintenance therapy of capecitabine (1,000 mg/m²twice a day from days 1-14, every 3 weeks) or only observation until disease progression. The primary endpoint was PFS, which was defined as the interval between initial treatment and the first documentation of disease progression or death. Result: The intent-to-treat population comprised of 274 patients (capecitabine maintenance, n=136; observation, n=138). There were no significant differences in baseline characteristics between capecitabine maintenance group and observation group. The median follow-up was 29.0 months (range, 0-62.5 months). Median PFS in capecitabine maintenance group was significantly longer than observation group (10.43 [95% confidence interval (CI) 9.70 to 12.23] vs. 7.82 [95% CI 7.00 to8.60] months; P<0.0001). The secondary endpoint of median OS in capecitabine maintenance group was longer than observation group, but not statistically significant (23.17 [95% CI 21.30 to 25.63] vs. 19.73 [95% CI 17.77 to 22.60] months; P=0.2548). In the subgroup analysis, PFS in patients treated with XELOX or FOLFOX was significantly longer than the relevant observation group (10.37[95% confidence interval (CI) 9.30 to 13.20] vs. 7.82 [95% CI 6.00 to 9.00] months; P% confidence interval (CI) 9.60 to 12.23] vs.7.82 [95% CI 7.03 to 8.93] months; P=0.0013, respectively). There was no significant difference between XELOX or FOLFOX and the relevant observation group with respect to OS. Similar safety profiles were observed in both arms. The most common grade 3 or 4 toxicities in capecitabine maintenance versus observation were neutropenia, hand–foot syndrome, and mucositis. Conclusion: Maintenance therapy with single agent capecitabine after induction of XELOX or FOLFOX seems beneficial in mCRC, demonstrating a prolonged PFS with acceptable toxicities.

Key Words: Colorectal cancer  Maintenance therapy  capecitabine