Neoadjuvant therapy of bevacizumab in combination with oxaliplatin and capecitabine (XELOX) for patients with metastatic colorectal cancer with unresectable liver metastases: a phase II, open‐label, single‐arm, noncomparative trial

Abstract

Aim: This phase II, open-label study evaluated the efficacy and safety of neoadjuvant therapy with bevacizumab plus XELOX (capecitabine and oxaliplatin) for untreated metastatic colorectal cancer with unresectable liver metastases and assessed conversion of unresectable to resectable metastases after neoadjuvant treatment. Methods:Patients received bevacizumab 5 mg/kg and oxaliplatin 85 mg/m 2 on day 1, and capecitabine 1000 mg/m 2 twice daily on days 1-5 followed by 2 days of rest in a 14-day cycle for 12 cycles; bevacizumab was excluded in cycles 6 and 7. Patients were later divided into resected and unresected groups, depending upon whether they underwent curative resection after chemotherapy. Efficacy and safety were evaluated.Results: Of 45 patients enrolled, 17.8% completed the study. The resection rate of liver metastases after neoadjuvant therapy was 42.2%. The median time to disease progression was 10.1 and 8.7 months in the resected and unresected groups, respectively (P = 0.1341). Response rate was significantly higher in the resected (47.4%) versus the unresected group (34.6%; P = 0.0010), and seven patients achieved complete response (resected group). Overall, 94.3% of adverse events were of mild or moderate severity, and grade ≥3 adverse events occurred in 4.3% and 7.3% of patients in the resected and unresected groups, respectively. The most common adverse events in both groups were palmar-plantar erythrodysesthesia syndrome, decreased appetite, thrombocytopenia, peripheral neuropathy, fatigue, diarrhea, vomiting, proteinuria and nausea. Conclusion:Neoadjuvant therapy with bevacizumab plus XELOX was well tolerated and effective in previously untreated metastatic colorectal cancer patients with initially unresectable liver metastases. K E Y W O R D Sbevacizumab, liver metastases, metastatic colorectal cancer, neoadjuvant therapy, XELOX

Survival Outcomes in Unresectable Metastatic Rectal Cancer Patients after both Primary Site Resection and Chemoradiotherapy: A Population-based Study

“…In the nal cohort, 270 (60.3%) metastatic rectal cancer patients did not receive hepatic resection and the median survival in this group was 37.0 months with 2-year, 5-year OS 68.5% and 32.9%. Compare with other studies [24,25], the overall survival results of the unresectable metastatic rectal cancer patients in this study were satisfactory. After comparing the inclusion criteria of our study to the others, we think the main difference is that we added radiotherapy to our inclusion criteria, and also the constantly updated chemotherapy and radiotherapy play a signi cant role in the improvement of survival outcomes, especially the application of the total neoadjuvant therapy (TNT) approach in the recent years.…”

Comprehensive review of targeted therapy for colorectal cancer

“…While perioperative administration of bevacizumab and chemotherapy for patients with liver metastatic CRC might be tolerable and helpful in prolonging survival, several phase II trials showed that recurrence was unavoidable, which lacks further validation. [457][458][459][460] As for locally advanced rectal cancer, abundant phase II studies have been conducted for the neoadjuvant use of anti-EGFR or anti-VEGF therapy, with pooled estimated pCR values of 27% and 14% being reported for bevacizumab-and cetuximab-relevant regimens, respectively, via a meta-analysis of 32 previous studies. 448 Although newer trials echoed the results from metaanalysis, 461 to elucidate whether the targeted agents are truly effective in the neoadjuvant setting still requires larger population-based head-to-head, time-to-event data.…”

Beyond the Knife: The Evolving Nonsurgical Management of Oligometastatic Colorectal Cancer

“…One prospective phase II study of 89 patients with hepatic metastases, of varying histologic types (34 CRCs), used protons to doses of 30 to 50 gray equivalents in five fractions (BED, 48-100 Gy; relative biologic effectiveness, 1.1) and had a median follow up of 30.1 months. 74 There were no CTCAE grade 3 or greater toxicities, and 1-and 3-year local control rates were 71.9% and 61.2%, respectively. Interestingly, as suggested by other investigators using SBRT with photons, 41 CRC metastases in the photon-beam therapy study had worse local control than did other tumors.…”

“…Interestingly, as suggested by other investigators using SBRT with photons, 41 CRC metastases in the photon-beam therapy study had worse local control than did other tumors. 74 Somatic analyses showed that tumors with mutant KRAS and TP53 tumors were more radioresistant than tumors wild-type for the same genes, and that mutation of the KRAS oncogene was a strong predictor of poor local control. This study is an important demonstration that proton-beam therapy safe and effective to treat oligometastases from mCRC.…”