Stabilization of Liver Metastases of CRC with Trifluridine/Tipiracil in 3rd Line Therapy – Case Study
We present a case study of a man born in 1944 who underwent resection of the rectosigmoid for multiple adenocarcinomas in February 2016. Subsequently discovered liver metastases were managed with several lines of palliative therapy in combination with repeated surgical resections. Trifluridine/tipiracil administered in the 3rd line represents a well-tolerated oral treatment for this patient, on which he achieved disease stabilization.
Medical History
The patient has a history of arterial hypertension compensated by a fixed triple combination of antihypertensive drugs, is being monitored in urology after radiotherapy for prostate cancer in 2009, still without recurrence, and in ENT after excision of basal cell carcinoma and carcinoma in situ in the area of the left ear in 2014, also without recurrence.
The patient does not smoke, consumes at most 1 beer per day, and denies any allergies. There is a history of colorectal cancer in his mother and brother. He has 2 healthy children, lives with his wife, and previously worked in a chemical plant, now retired.
Resection of Rectosigmoid Adenocarcinoma
In February 2016, a laparoscopic resection of the rectosigmoid with colorectal anastomosis was performed. Histological examination showed multifocal invasive moderately differentiated colorectal adenocarcinomas not extending beyond the edges of the surgical resection. No signs of metastatic involvement were found in the 18 lymph nodes examined.
This was a tumor with a non-mutated RAS oncogene (wild type). Adjuvant chemotherapy was not indicated, and the patient continued to be monitored in a local proctology clinic.
Dissemination of the Disease to the Liver and Response to Systemic Treatment
In October 2016, the patient was referred to a comprehensive oncology center for newly discovered disease generalization to the liver. There were 11 lesions, the largest approximately 3 cm in diameter. The local colonoscopic finding was free of signs of recurrence up to the area of the cecum. The levels of tumor markers CEA and CA19-9 had increased compared to pre-surgery levels. Therefore, in October 2016, palliative 1st line chemotherapy with the FOLFOX6 regimen was started, and targeted anti-EGFR therapy with panitumumab was added from the 3rd cycle.
CT scan in March 2017 showed regression of liver findings, and liver MRI in April 2017 confirmed the presence of 12–15 lesions up to 5 mm in size. The patient continued chemotherapy. Based on PET/MRI examination conducted in June 2017, further significant shrinkage of the lesions and decreased metabolic activity was found. No metastatic lesions were found outside of the liver, and no local tumor recurrence was detected.
Subsequent Disease Progression and 2nd Line Treatment
In November 2017, however, MRI showed progression of liver lesions. In the 2nd line of treatment, the patient received the FOLFIRI + bevacizumab regimen. Due to diarrhea, the dose of irinotecan was reduced to 75%, and treatment was repeatedly delayed due to hematotoxicity. Ultimately, the patient completed 12 cycles of FOLFIRI and continued with bevacizumab monotherapy.
In June 2018, PET/MRI showed only one liver metastasis of 18 mm in diameter. In September 2018, the patient underwent metastasectomy, in September 2019 radiofrequency ablation (RFA) of a newly detected lesion in the right liver lobe, and in August 2020 radio-interventional chemoembolization of the liver for newly detected lesions resembling metastases on CT. In November 2020, CT showed regression of metastases, absence of new lesions, and no local recurrence.
Stabilization with 3rd Line Treatment
In January 2021, disease generalization was again found with new metastases in the right liver lobe. Thus, 3rd line chemotherapy was indicated. Since February 2021, the patient has been taking trifluridine/tipiracil (Lonsurf) p.o. twice daily on days 1–5 and days 8–12 of each 28-day cycle. In March 2021, repeated transarterial chemoembolization of the lesion visible on CT before the necrotic area after RFA was performed.
According to CT findings in July 2021, disease stabilization was achieved. The finding was considered radiofrequency and surgically untreatable. The patient continues to take trifluridine/tipiracil. The treatment is accompanied by grade 2 neutropenia, requiring growth factor support, but is otherwise very well tolerated. The next control CT scan was scheduled for November 2021 at the time of case study preparation.
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Source:
- Čmuchařová E. Lonsurf – Case Study. Comprehensive Oncology Center of Masaryk Hospital in Ústí nad Labem, 8. 12. 2021. [presentation]
- Summary of Product Characteristics for Lonsurf
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