Irinotecan Plus Raltitrexed as Second-line Treatment in Advanced Colorectal Cancer Patients

Irinotecan and raltitrexed are active against advanced colorectal cancer (ACC), act through different mechanisms, and have only partially overlapping toxicity profiles. The purpose of this study is to evaluate efficacy and safety of irinotecan plus raltitrexed as second-line treatment in advanced colorectal cancer patients.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

* life expectancy of at least 3 months;
* histological and/or cytological confirmation of ACC;
* disease progression while on first-line palliative oxaliplatin \& fluoropyrimidine chemotherapy or relapse within 6 months after adjuvant oxaliplatin \& fluoropyrimidine chemotherapy;
* wash-out time of 4 weeks after the last chemotherapy infusion or radiotherapy，and observed lesions not in the radiotherapy target；
* at least one measurable objective tumor lesion by spiral CT examination, the maximum diameter ≥ 1cm（according to RECIST 1.1）；
* ECOG performance status 0-1；
* satisfactory main organ function，laboratory test must meet the following criteria: hemoglobin (HGB) ≥90g/L, neutrophil count（ANC） ≥1.5×109/L, platelet count（PLT） ≥90×109/L, Serum creatinine（CR）≤1.5 upper normal limitation (UNL)，creatinine clearance rate (CCr) ≥60ml/min, total bilirubin (TBil) ≤1.5 upper normal limitation (UNL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 UNL (For patients with liver metastasis, the AST/ALT must be ≤5.0 UNL);
* For women with child bearing potential, a negative serum or urine pregnancy test result should be obtained before enrollment
* written informed consent.

Exclusion Criteria:

* prior exposure to irinotecan or raltitrexed;
* chronic enteropathy on unresolved bowel obstruction;
* Pregnant or lactated women;
* previous malignant disease other than carcinoma in situ of the cervix or basal cell carcinoma of the skin;
* Concurrent administration of any other investigational drug, or have been enrolled in other clinical trial with investigational drug treatment within the 30 days of start of study treatment；
* cerebral metastases or leptomeningeal carcinomatosis;
* severe or uncompensated concomitant medical conditions.
* Unsuitable for the study or other chemotherapy determined by investigator.

• RESULTChiara S, Nobile MT, Tomasello L, Acquati M, Taveggia P, Murolo C, Percivale P, Rosso R. Phase II trial of irinotecan and raltitrexed in chemotherapy-naive advanced colorectal cancer. Anticancer Res. 2005 Mar-Apr;25(2B):1391-6. PMID 15865096
• RESULTFeliu J, Salud A, Escudero P, Lopez-Gomez L, Pericay C, Castanon C, de Tejada MR, Rodriguez-Garcia JM, Martinez MP, Martin MS, Sanchez JJ, Baron MG; Oncopaz Cooperative Group and Associated Hospitals. Irinotecan plus raltitrexed as first-line treatment in advanced colorectal cancer: a phase II study. Br J Cancer. 2004 Apr 19;90(8):1502-7. doi: 10.1038/sj.bjc.6601713. PMID 15083176
• RESULTAparicio J, de las Penas R, Vicent JM, Garcera S, Llorca C, Maestu I, Yuste AL, Farres J. Multicenter phase I study of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer. Oncology. 2002;63(1):42-7. doi: 10.1159/000065719. PMID 12187070
• RESULTCarnaghi C, Rimassa L, Garassino I, Zucali PA, Masci G, Fallini M, Morenghi E, Santoro A. Irinotecan and raltitrexed: an active combination in advanced colorectal cancer. Ann Oncol. 2002 Sep;13(9):1424-9. doi: 10.1093/annonc/mdf229. PMID 12196368
• DERIVEDCheng Y, Teng Z, Zhang Y, Jin B, Zheng Z, Man L, Wang Z, Teng Y, Yu P, Shi J, Luo Y, Wang Y, Zhang J, Zhang H, Liu J, Chen H, Xiao J, Zhao L, Zhang L, Jiang Y, Chen Y, Zhang J, Wang C, Liu S, Qu J, Qu X, Liu Y. Irinotecan plus raltitrexed as second-line treatment in locally advanced or metastatic colorectal cancer patients: a prospective open-label, single-arm, multi-center, phase II study. BMC Cancer. 2024 Sep 2;24(1):1082. doi: 10.1186/s12885-024-12831-4. PMID 39223545