Oxaliplatin/5-FU without Leucovorin Chemotherapy in Metastatic Colorectal Cancer

Shim, Byoung Yong; Lee, Kang Moon; Cho, Hyeon-Min; Kim, Hyun Jin; Cho, Hong Joo; Yang, Jung–Min; Kim, Jun-Gi; Kim, Hoon-Kyo

doi:10.4143/crt.2005.37.4.212

Cited by 4 publications

(4 citation statements)

References 28 publications

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“…Oxaliplatin-based regimens have recently become the gold standard in postoperative adjuvant chemotherapy for patients with stage III CRC [14]. However, the choice of an appropriate treatment strategy and decision on therapy duration depend on the associated cumulative neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Features and Oncological Outcomes of Early and Late Recurrence in Stage III Colorectal Cancer Patients after Adjuvant Oxaliplatin-Based Therapy

Chang

Tsai

Chen

et al. 2023

Journal of Oncology

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Aims. An adjuvant oxaliplatin-based regimen is the standard of care for patients with stage III colorectal cancer (CRC). Few reports have compared the clinicopathological features and oncological outcomes of such treatment between patients with early (≤1 year) and late recurrence (>1 year). Methods. Between January 2012 and December 2019, CRC recurred in 128 (24.1%) of 531 patients with consecutive stage III CRC after they received curative resection and an adjuvant oxaliplatin-based regimen. The clinicopathological features and oncological outcomes of the 128 patients were analyzed retrospectively. Results. The median follow-up period after the first chemotherapy cycle was 35.0 months (range, 7–100.9), and the median recurrence time was 16.1 months. Forty-seven patients (36.7%) had an early recurrence and eighty-one patients (63.3%) had a late recurrence. Compared with patients with late recurrence, those with early recurrence were mostly younger (median: 58 vs. 64 years, p = 0.009 ), had less oxaliplatin-based therapy cycles (median: 8 vs. 12 cycles, p < 0.001 ), and had a shorter overall survival time (median: 23.3 vs. 39.7 months, p < 0.001 ). The area under the curve of patient age and chemotherapy cycles for predicting early recurrence was 0.629 and 0.705 ( p = 0.015 and p < 0.001 ), respectively. The receiver operating characteristic curve analysis demonstrated that the cutoff level for patient age was 57 years and the number of chemotherapy cycles was 8. A multivariate analysis revealed that patient age ≤57 years and oxaliplatin-based therapy ≤8 cycles were independent risk factors for early recurrence (odds ratio (OR) = 3.049, p = 0.022 ; OR = 4.995, p = 0.002 ). These factors were associated with an approximately 77.8% risk of recurrence within 1 year, compared with the 21.5% risk associated with patient age >57 years and oxaliplatin-based therapy >8 cycles (p = 0.003). Conclusion. Patients with early recurrence had poorer survival than those with late recurrence. If >8 cycles of oxaliplatin-based therapy can be administered without disease progression, then patients with stage III CRC would have a lower risk of early recurrence.

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Section: Discussionmentioning

confidence: 99%

Clinicopathological Features and Oncological Outcomes of Early and Late Recurrence in Stage III Colorectal Cancer Patients after Adjuvant Oxaliplatin-Based Therapy

Chang

Tsai

Chen

et al. 2023

Journal of Oncology

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“…One established chemotherapy regimen for the treatment of CRC is FOLFOX, which consists of a combination of leucovorin (FOL), 5-FU (F) and oxaliplatin (OX). According to experimental data, there is controversy concerning whether monotherapy or combination therapy is better [5] [6]. Although chemotherapy kills most cells within a tumor, it has been experimentally demonstrated that is ineffective in cancer stem cells (CSCs), which exhibit resistance to chemotherapy [7].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of 5-FU or Oxaliplatin Monotherapy over Combination Therapy in Colorectal Cancer

Toloudi¹,

Apostolou²,

Papasotiriou³

2015

JCT

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Recent clinical and research development supports the use of 5-fluorouracil in combination with oxaliplatin for the treatment of patients with advanced colorectal cancer (CRC). 5-Fluorouracil (5-FU), which is as an anti-metabolite, is a widely used cytostatic drug. Although the rate of response, quality of life and overall survival differs between CRC patients, the above combination remains a widely used chemotherapeutic regimen. In some cases, a cancer stem cell (CSC) population may resist the majority of chemotherapeutic models. This study investigated if monotherapy is more efficacious than 5-fluorouracil and oxaliplatin combined for the treatment of CRC, using a CRC cell line and a CSC-like line. Cell viability was evaluated by cellular-based assays, and quantitative polymerase chain reaction (q-PCR) assays were performed to assess the expression of specific genes (TYMS, DNMT1, NANOG, DHFR, SHMT1, ERCC1, DPYD) correlated with 5-FU and oxaliplatin resistance. We observed that 5-fluorouracil was more effective in both CRC and CSCs. This find-ing proved the hypothesis that, in some cases, monotherapy may be more successful in CRC treatment than a drug combination that may be cytotoxic and inflict adverse side effects.

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“…The combination of 5-FU and oxaliplatin is one of the most commonly used combinations. However, some studies found that monotherapy was more effective than the combination [4] [5], while other evidences suggested that the metronomic application of chemotherapy, i.e., continuous administration of low-dose chemotherapeutic agents without extended intervals, could be more efficient [6]. Resistance to chemotherapy may be associated with the existence of cancer stem cells (CSCs), which comprise a subpopulation of circulating tumor cells that may detach from the primary tumor and enter the blood circulation, thus creating secondary tumors [7] [8].…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Changes in Colorectal Cancer during Metronomic Chemotherapy and High-Concentration Drug Administration

Apostolou¹,

Toloudi²,

Kalliara³

et al. 2015

JCT

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5-fluorouracil (5-FU) and oxaliplatin, either alone or in combination, are widely used in chemotherapy for advanced colorectal cancer. Among chemotherapeutic strategies, metronomic chemotherapy has recently demonstrated promising efficacy against otherwise chemoresistant neoplasms. However, data on the efficacy of metronomic applications in cancer stem cells are lacking. This cell population is characterized by resistance to most chemotherapeutic models. In this study, we investigated the efficacy of metronomic chemotherapy and compared it with high-concentration administration of 5-FU and oxaliplatin and their combination in colon adenocarcinoma cells and colon cancer stem cells. We assessed changes in expression levels of specific genes involved in 5-FU and oxaliplatin resistance (thymidylate synthase, DNA (cytosine-5)-methyltransferase 1, dihydrofolate reductase, serine hydroxymethyltransferase, DNA excision repair protein, dihydropyrimidine dehydrogenase) in relation to drug administration schedule using quantitative real-time polymerase chain reaction. We also examined changes in cell viability. Metronomic chemotherapy showed greater efficacy in gene expression levels in colorectal cancer cells, while high, singleconcentration administration was more effective in colon cancer stem cells. Regarding cell viability, no significant change was observed between metronomic and single-dose treatments. These results suggest that metronomic chemotherapy may be more effective than high-dose chemotherapy in some patients with colorectal cancer, though high, single-concentration administration may be more effective against cancer stem cells.

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Oxaliplatin/5-FU without Leucovorin Chemotherapy in Metastatic Colorectal Cancer

Cited by 4 publications

References 28 publications

Clinicopathological Features and Oncological Outcomes of Early and Late Recurrence in Stage III Colorectal Cancer Patients after Adjuvant Oxaliplatin-Based Therapy

Clinicopathological Features and Oncological Outcomes of Early and Late Recurrence in Stage III Colorectal Cancer Patients after Adjuvant Oxaliplatin-Based Therapy

Efficacy of 5-FU or Oxaliplatin Monotherapy over Combination Therapy in Colorectal Cancer

Gene Expression Changes in Colorectal Cancer during Metronomic Chemotherapy and High-Concentration Drug Administration

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