Colorectal Cancer (CRC) is the most common malignancy, CRC is Korea's second-largest common malignant tumors, accounting for 13.5% of all new cancers. 30% for advanced CRC patients diagnosis, 50% patients undergoing curative surgery, but will eventually transfer occurs.
In the past 40 years, 5-fluorouracil combined with folic acid in the treatment of metastatic CRC is the mainstream treatments, overall response rate (ORR) 20%-30%. Since the late 90 's of Oxaliplatin and irinotecan appears, used in combination with 5-fluorouracil and folic acid significantly improved response rate and survival.
Two kinds of chemotherapy in order to use in clinical practice, can also be combined with targeted drugs for treatment of metastatic CRC. But Oakland thalidomide and Platinum or irinotecan +5-fluorouracil + folic acid treatment failed, lack of an effective third-line chemotherapy.
Capecitabine is drugs of fluorouracil, first converted to 5-fluorouracil in the tumor location. Capecitabine in tumor xenograft animal model of effective, even resistant to 5-fluorouracil in cancer as well. Capecitabine monotherapy first-line treatment of metastatic CRC,ORR about 20%.
Security with Capecitabine is superior to 5-fluorouracil + folic acid diarrhea, gastritis, baldness, or 3/4 neutropenia significantly decreased. FOLFOX or FOLFIRI treatments fail, Capecitabine still retains a certain activity ORR 5%, 60% disease control rate, toxicity can be tolerable.
Involved in purine and pyrimidine metabolism of folic acid may increase the toxicity of 5-fluorouracil and therapeutic effects. Preclinical studies have shown that folic acid increased Capecitabine activity without increasing side effects. Korea doctors Dae Ro Choi study published in the journal Cancer Chemother Pharmacol, third-line therapy study on Capecitabine + folic acid to Oxaliplatin and irinotecan-resistant metastatic CRC.
Patients in the study received oxaliplatin-containing or irinotecan chemotherapy or stopping progression within 6 months, given Capecitabine 825mg/m2,2/day, 30mg,2/day of folic acid, used for 2 weeks, 1 week break.
2011.7-2014.6 recruited 25 patients, 3 patients PR,11 patients SD,ORR12%, disease control rate of 56%. A median follow-up of 6.8 months, progress was 2.8 months, OS7.1, the most common non-haematological toxicity was hand-foot syndrome, followed by diarrhea and mucositis. 2 patients had grade 3 hand-foot syndrome, 1 patient had grade 3 mucositis. Mild hematologic toxicity, 1 patient had grade 3 thrombocytopenia.
Study on the assessment of Capecitabine combined with folic acid in third-line treatment of metastatic CRC effectiveness and toxicity. The programme shown on Iraqi State for Topotecan or resistant to Oxaliplatin for metastatic CRC patients are still appropriate to the activity and toxicity can be tolerated. Capecitabine alone does not have cells, occurs after the required transformation in the tumor.
Preclinical studies have shown combined with folic acid could increase Capecitabine anti-tumor effect, in this study, a lower dose of Capecitabine ORR 12%,DCR 56%, secondary endpoint TTP and OS 2.8 and 7.1 months. These results and other studies in the higher dose of Capecitabine (1250mg/m2) of treatment results were comparable. Worth-mentioning is under the salvage treatment, 25 3 patients who show PR.
Review of the literature, only one phase II trials study on Capecitabine in combination with folic acid. As first-line treatment in the study, three Capecitabine dose in the treatment advanced CRC, group a 1331mg/m2/d continued use; used b 2510mg/m2/d 2 weeks 1 week break; Group c 1657mg/m2/d, used for 2 weeks, 1 week break, combining folic acid 60mg/d. ORRs, and no significant difference in toxicity between the three groups. Results showed that low-dose Capecitabine combined with LV in treatment of patients with metastatic CRC is feasible.
The joint is well tolerated, low toxicity, the most common non-hematologic toxicities were hand-foot syndrome (HFS), mucosal inflammation and diarrhea. 2 3 HFS,1 those who grade 3 mucositis occurred. Hematologic toxicity low, only 1 grade 3 thrombocytopenia occurs.
In short, combined with low dose of Capecitabine with folic acid treatment with irinotecan or Capecitabine-resistant metastatic CRC demonstrated therapeutic activity and the tolerance of side effects. Oral folic acid appears to reduce the use of Capecitabine General.