Overview
This is a phase II, single-center, prospective trial aimed to investigate the efficacy and safety of a modified regimen of trifluridine/tipiracil plus bevacizumab in refractory metastatic colorectal cancer. Patients will be treated with trifluridine/tipiracil (17.5 mg/m2 dose orally twice daily, d1-10, every 14-days) plus bevacizumab (5mg/kg dose intravenously once at day 1, every 14-days). The study treatment will be administered until progression of disease, intolerable toxicity or withdraw of consent.
Description
The treatment options as third-line therapy for metastatic colorectal cancer patients are limited. Trifluridine/tipiracil (TAS-102) plus bevacizumab has been approved in colorectal cancer for patients who are refractory to or intolerant of standard chemotherapy. However, the toxicity of trifluridine/tipiracil at standard dose a clinical concerned issue. Modifications of dose and treatment cycle of trifluridine/tipiracil have been investigated, and show promising effect to reduce the toxicity. In this study, patients with refractory metastatic colorectal cancer who have disease progression after at least 2 standard regimens will be treated with low-dose trifluridine/tipiracil plus bevacizumab. Trifluridine/tipiracil will be given at a 17.5 mg/m2 dose orally twice daily in a 14-day cycle consisting of 10 treatment days/4 rest days. Bevacizumab will be given at a 5mg/kg dose intravenously once at day 1 in a 14-day cycle. This regimen will be administered until progression of disease, intolerable toxicity or withdraw of consent.
Eligibility
Inclusion Criteria:
- age over 60 years old, male and female
- histologically confirmed adenocarcinoma of the colon or rectum
- patients with metastatic or advanced unresectable diseases who had received two or more previous chemotherapy regimens or intolerance to last regimen
- with or without measurable lesions
- ECOG 0 to 2, expected survival time over 3 months
- Enough organ functions that can tolerate treatment: Absolute neutrophil count (ANC) ≥1.5x109/L, White blood count ≥3.5x109/L, Platelets ≥75x109/L, Hemoglobin (Hb) ≥80g/L, ALT/AST ≤2.5x ULN (for patient with liver metastasis ALT/AST ≤5x ULN), Serum bilirubin ≤1.5x ULN, Serum creatinine ≤1.5x ULN.
- Signed informed consent and willing to follow the study protocol
Exclusion Criteria:
- symptomatic metastases of central nervous system
- other primary malignancies
- uncontrollable comorbidities, such as hypertension, thrombotic diseases, chronic kidney disease
- organ functions that cannot tolerate study treatment
- bowel obstruction or other conditions affecting oral administration
- allergic to study medication
- other conditions that patients are unsuitable for this study assessed by the investigators