Complete Response with Modified FLOX in Metastatic Colon Cancer: A Case Report

Abstract

Introduction

Colorectal cancer (CRC) is one of the main causes of death by cancer. Patients diagnosed with colon adenocarcinoma and unresectable liver metastases have a poor prognosis, with a median overall survival (OS) of 24 months.

Case Presentation

We herein report the case of a 7-year sustained complete response (CR) with 2 cycles of modified 5-fluorouracil plus oxaliplatin (mFLOX) in a metastatic setting. The patient is a White Brazilian male aged 59 years.

Conclusion

There is scarce evidence on the clinical evolution of non-operable patients with metastasis to establish a definitive cure only with a chemotherapy regimen, without complimentary liver resection. The patient herein reported achieved CR with only two cycles of treatment, which is not usual in this scenario. He was deemed non-operable because of the number and position of the lesions detected before the start of chemotherapy.

Keywords

colorectal cancer - fluorouracil - oxaliplatin - complete response

Introduction

In Brazil, for the triennium 2020 to 2022, approximately 20,520 cases of colorectal cancer (CRC) were estimated in men, and 20,470, in women. Despite the falling mortality rate in recent decades, CRC is still among the leading causes of death. In men and women, it represents the third leading cause of death by cancer.[1]

Patients diagnosed with colon adenocarcinoma and liver metastasis have a poor prognosis, with a median overall survival (OS) of 24 months.[2] The modified 5-fluorouracil plus oxaliplatin (mFLOX) protocol consists in leucovorin (LV; 20 mg/m²) in combination with a weekly bolus of 5-fluorouracil (5-FU; 500 mg/m²) for 6 consecutive weeks, and oxaliplatin (85 mg/m²) on days 1, 15, and 29, every 8 weeks.

In the present case report, we report the successful treatment, with sustained complete response (CR), of a male patient aged 59 years, who had been diagnosed with adenocarcinoma of the ascending colon with non-resectable liver metastases and was treated with the mFLOX protocol.

Case Description

A White male patient aged 59 years, with type-2 diabetes mellitus and no familial history of cancer, searched the emergency medical service complaining of paradoxical diarrhea, emesis, and recurrent, cramping abdominal pain. He did not present medical history of hepatitis or other infectious chronic diseases. During the investigation, a colonoscopy with biopsy diagnosed a well-differentiated tubulovillous adenocarcinoma in the ascending colon, with 90% of lumen obstruction. The patient was referred to Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP), in the city of São Paulo, Brazil, for oncologic treatment. The imaging evaluation with computed tomography (CT), performed in August 2015, revealed a tumor in the T3N2bM1 stage according to the seventh edition of the American Joint Committee on Cancer (AJCC) cancer staging manual, with a 4.5-cm stenotic lesion in the right colon. The liver presented multiple metastatic nodules in both lobes, measuring up to 3.0 cm. The arterial and venous phases were compatible with tumoral secondary involvement. The patients baseline serum level carcinoembryonic antigen (CEA) was of 144 ng/mL.

Due to intestinal subocclusion, a laparoscopic colectomy was performed. The surgical anatomopathological examination revealed moderately differentiated colon adenocarcinoma ([Fig. 1]), with free surgical margins, and metastases in 11 of 22 dissected lymph nodes. The evaluation of the molecular profile showed KRAS gene mutation, with G13D with NRAS and BRAF wild type. Immunohistochemistry showed PMS2 + , MLH1 + , MSH2 + , and MSH6 + , defining a proficient mismatch repair (pMMR) tumor.

Fig. 1 Surgical anatomopathological examination showing a case of moderately differentiated colon adenocarcinoma.

After surgical recovery, the patient underwent the mFLOX chemotherapy protocol, which consisted in a weekly bolus of 5-fluorouracil (500 mg/m²) and leucovorin (20 mg/m²) for 6 consecutive weeks and oxaliplatin (85 mg/m²) at weeks 1, 3, and 5 once every 8 weeks per cycle. The levels of CEA decreased to 18 ng/mL after cycle 1 (C1) and 4.4 ng/mL after cycle 2 (C2) ([Fig. 2]). The patient finished two complete cycles with no significant toxicity in February 2016.

Fig. 2 Levels of carcinoembryonic antigen (CEA) in the blood (normal reference: 0–5 µg/L).

The imaging exams performed for restaging after C2 showed CR. After a discussion, the multidisciplinary board did not recommend complementary surgery due to the CR in all lesions, and considering the miliary original distribution occupying all hepatic segments.

The patient started clinical follow-up with thoracic CT and abdominal and pelvic magnetic resonance imaging (MRI) scans, assessment of the level of CEA, and clinical evaluation to monitor for possible tumor regrowth. The patient underwent imaging exams every 2 to 3 months in the first 2 years. Then, he was submitted to a clinical evaluation with an assessment of the level of CEA every 3 months and imaging exams every 6 months until 5 years of follow-up. Considering the sustained CR, the actual follow-up is yearly. The patient remains in with no evidence of tumor recurrence ([Fig. 3]).

Fig. 3 (A, B) Baseline computed tomography (CT) scan performed in August 2015; (C, D) CT scan performed after 2 cycles of modified 5-fluorouracil plus oxaliplatin (mFLOX) in May 2016; (E, F) magnetic resonance imaging (MRI) scan performed at the last follow-up in October 2022.

Discussion

Most diagnosed cases of metastatic colon cancers presenting with liver metastasis are inoperable without systemic chemotherapy treatment.[3] Among the patients who achieve surgical resection of liver metastases, only 20% will be definitively cured at 10 years of follow-up.[4] Complete response is observed in 3% of patients treated with fluoropyrimidine and oxaliplatin regimens.[5] There is little evidence about the clinical evolution of non-operable patients with metastasis to establish a definitive cure only with a chemotherapy regimen, without complimentary liver resection.

The patient herein reported achieved CR with only two cycles of treatment, which is not usual in this scenario; he was deemed non-operable because of the number and position of the lesions detected before the start of chemotherapy.

There are few reports of complete response with the use of other therapeutic modalities, and they involve specific alterations in tumor drive and treatment using target therapy: In one study,[6] the patients achieved CR after immunotherapy action in patients with high-frequency microsatellite instability (MSI-H), and another study[7] reported CR after regorafenib in the same setting.

The mFLOX regimen is widely available and showed efficacy equivalent to that of other regimens used for metastatic colon cancer.[8] As mFLOX does not use an infusion pump, it has a considerably lower cost than that of modified 5-fluorouracil plus leucovorin plus oxaliplatin (mFOLFOX) in developing countries.[9] In the case herein reported, the mFLOX regimen resulted in CR in a pMMR metastatic patient with no evidence of disease recurrence after 7 years of follow-up.

Conflict of Interests

The authors have no conflict of interests to declare.

Acknowledgments

The authors would like to thank Dr. Leonardo Cardili and Dr. Felipe Rigaud de Amorim, from Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira, for their assistance in selecting pathology and radiology images for the present case report.

Ethical Approval and Consent to Participate

The present study was approved by the institutional Ethics in Research Committee, and the patient signed the informed consent form.

Consent for Publication

The patient consented to the publication and signed the informed consent form.

Authors' Contributions

CMVM: conceptualization and writing – review & editing; and DAG: writing – original draft. Both authors approved the final manuscript.

• References

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Publication History

Received: 04 October 2024

Accepted: 29 October 2024

Article published online:
29 December 2025