Open Access

ARTICLE

A Phase II Clinical Trial of Chemotherapy Rechallenge with or without Targeted Therapy in Refractory Metastatic Colorectal Cancer

Chenchen Wang^1,2, Mingzhu Huang^1,2, Wenhua Li^1,2, Xuedan Sheng^1,2, Xiaoying Zhao^1,2, Xiaodong Zhu^1,2, Zhiyu Chen^1,2, Zhe Zhang^1,2, Haiming Li^2,3, Weijian Guo^1,2,*

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 2026, 34(9), 25 https://doi.org/10.32604/or.2026.084378

Received 21 April 2026; Accepted 02 July 2026; Issue published 13 August 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.

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