Open Access
ARTICLE
A Phase II Clinical Trial of Chemotherapy Rechallenge with or without Targeted Therapy in Refractory Metastatic Colorectal Cancer
Chenchen Wang1,2, Mingzhu Huang1,2, Wenhua Li1,2, Xuedan Sheng1,2, Xiaoying Zhao1,2, Xiaodong Zhu1,2, Zhiyu Chen1,2, Zhe Zhang1,2, Haiming Li2,3, Weijian Guo1,2,*
1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
3 Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
* Corresponding Author: Weijian Guo. Email: 
Oncology Research https://doi.org/10.32604/or.2026.084378
Received 21 April 2026; Accepted 02 July 2026; Published online 21 July 2026
Abstract
Background: Patients with refractory metastatic colorectal cancer (mCRC) face limited treatment options after failure of standard therapies. This single-arm, phase II study aimed to evaluate the efficacy and safety of rechallenge strategies using previously effective regimens in late-line mCRC. Methods: Patients who progressed after ≥2 lines of prior chemotherapy, with a prior progression-free survival (PFS) ≥4 months and a ≥4-month treatment-free interval on that regimen were enrolled. Patients received rechallenge chemotherapy (oxaliplatin-, irinotecan-, or raltitrexed-based) with or without targeted agents (bevacizumab or cetuximab). Primary endpoint was investigator-assessed PFS. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: Forty-three patients were enrolled (31 received chemotherapy plus targeted agents; 12 received chemotherapy alone). One patient discontinued treatment, leaving 42 patients evaluable for tumor response. The median PFS and OS were 3.97 months (95% CI: 2.46–5.48) and 13.03 months (95% CI: 9.68–16.38), respectively, while the ORR and DCR were 2.4% and 61.9%. Subgroup analysis showed that patients receiving chemotherapy plus targeted agents had higher DCRs (80.0% for bevacizumab-based regimens and 72.7% for cetuximab-based regimens vs. 18.2% for chemotherapy alone;) and longer median PFS (4.17 and 4.50 months vs. 1.57 months, respectively). Grade 3 or 4 adverse events were reported in 39.5% of patients, with no severe adverse events or treatment-related deaths observed. Conclusion: Chemotherapy rechallenge strategies, particularly when combined with targeted agents, demonstrated promising clinical activity and acceptable safety in selected heavily pretreated patients with mCRC who previously achieved sustained disease control.
Keywords
Colorectal cancer; refractory disease; rechallenge therapy; clinical trial
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