Efficacy of Retreatment with Oxaliplatin-Based Regimens in Metastatic Colorectal Cancer Patients: The RETROX-CRC Retrospective Study

Abstract

Background: oxaliplatin with fluoropyrimidine is a “mainstay” regarding the upfront treatment of metastatic colorectal cancer (mCRC). In contrast, the efficacy and safety of oxaliplatin-based regimens in late-care settings have been poorly reported. Methods: we identified a real-world mCRC patient cohort who were re-treated with oxaliplatin, and in which clinicopathological features were retrospectively analyzed to identify efficacy–predictive determinants (RETROX-CRC study). Results: of 2606 patients, 119 fulfilled the eligibility criteria. Oxaliplatin retreatment response rate (RR) and disease control rate (DCR) were 21.6% (CI 14.4–31.0%), and 57.8% (CI 47.7–67.4). A trend towards better RR and DCR was observed among patients who had first oxaliplatin in an adjuvant setting; a poorer outcome was observed if two or more intervening treatments were delivered. Median progression-free survival (PFS) was 5.1 months (95%CI 4.3–6.1), reducing to 4.0 months (95%CI 3.07–5.13) if oxaliplatin was readministered beyond third-line (HR 2.02; 1.25–3.25; p = 0.004). Safety data were retrieved in 65 patients (54.6%); 18.5% (12/65) and 7.7% (5/65) had G3–4 toxicities. Toxicities led to discontinuation in 34/119 (28.6%). Conclusions: oxaliplatin retreatment produced further RR in around one-fifth of patients and DCR 57.8%. Efficacy decreased in more pre-treated patients and around one-third of patients discontinued treatment due to adverse events. Translational studies improving patient selection are warranted.

Third-line treatment patterns and clinical outcomes for metastatic colorectal cancer: a retrospective real-world study

“… 35 From the Retreatment with Oxaliplatin-Based Regimenin Metastatic Colorectal Cancers (RETROX-CRC) retrospective study collecting 119 mCRC patients, the ORR and DCR of oxaliplatin retreatment were recorded as 21.6% and 57.8%, respectively. 36 Our study also found that the DCR of chemotherapy ± targeted drugs in the third-line setting could reached 61.3%, and the survival of those patients was longer than that of patients receiving anti-angiogenic monotherapy, which was consistent with another Japanese study. 24 Conversely, a retrospective multicenter clinical analysis containing 105 patients with mCRC concluded that anlotinib ( n = 35) had better clinical efficiency as a third-line treatment than chemotherapy ( n = 35) and similar to fruquintinib or regorafenib ( n = 35).…”

Nomogram for predicting neutropenia in patients with esophageal, gastric, or colorectal cancer treated by chemotherapy in the first cycle

“…Esophageal cancer and gastrointestinal cancer account for nearly 20% of new global cancer cases, 21 and oxaliplatin- and fluoropyrimidine-based chemotherapy are still regarded as fundamental regimens, although several targeted therapies and immunotherapies have been applied. 22 The adverse effects of the treatment, including persistent peripheral sensory neuropathy and hematological adverse events, are inevitable and cannot be ignored. Grade 3 or higher neutropenia may lead to decreased quality of life, delays in treatment administration, dose reductions, or even lethal infections.…”

Chemotherapy re-use versus anti-angiogenic monotherapy as the third-line treatment of patients with metastatic colorectal cancer: a real-world cohort study

“…The clinical benefit rate of oxaliplatin or irinotecan re-challenge was reported to be 75.5% in an American cohort [ 23 ]. In another Italy RETROX-CRC retrospective study, oxaliplatin retreatment produced further response rate in around one-fifth of patients [ 24 ]. The results are controversial as to the comparison of the efficacy of chemotherapy to that of anti-angiogenic monotherapy.…”

“…In a pooled analysis exploring FOLFOX reintroduction, both response rate and PFS nearly doubled when the oxaliplatin-free interval was more than 6 months [ 34 ]. Researchers failed to reconstruct the oxaliplatin-free interval from the RETROX-CRC study, however, they found that the trend of better response to oxaliplatin retreatment in patients who used oxaliplatin as adjuvant therapy [ 24 ], which indicated longer time interval in some degree. In addition, chemotherapy rechallenge was more efficient in patients who achieved PR or SD in front-line therapies [ 22 ].…”