Clinical Analysis Of Oxaliplatin Combined With 5-Fluorouracil And Calcium Folinate In Treatment Of Colorectal Cancer

Colorectal cancer is one of the common malignant tumor in gastrointestinal track, found in rectum, sigmoid colon, cecum, descending and transverse colon. Recently with aging global population and the improvement of living standard, the morbidity of colorectal cancer increases rapidly in a speed of 4.2% annually in our country. The main therapy for colorectal cancer is a surgery combined with other treatments, however, it's hard to achieve curative resection below 5%, moreover, 50% patients will relapse within 5 years, and the rate of the secondary surgery more than is very low if relapse. Furthermore, some patients have already missed operation opportunities when diagnosed, which makes it impossible to get cured by surgery only. Even though no residual tumor is confirmed by pathology after radical resection, more than 40% patients will still die of recurrence. Therefore the adjuvent chemotherapy is very important for the patients with advanced colorectal cancer. The best effectiveness for 5-fluorouracil (5-Fu) discovered in 1957, has been achieved by increasing the biological response modifiers and changing the usage of it. The regimen of 5-Fu+LV is always the main adjuvant chemotherapy for colorectal cancer, but the efficacy and survival are not ideal. Recently, the application of new chemotherapy medicine, such as CPT-11, Oxaliplatin (L-OHP) , Xeloda, etc, and targeted therapy medicine, such as cetuximab, bevacizumab, etc, has made an obvious improvement of the prognosis of the patients with colorectal cancer and get the survival prolonged to 20 months or so. The increase of the available medicines and the transformation of regimen make clinical doctors confused. How to select the best regimen to improve patients' life quality and to prolong their live time effectively is the problem that needs to be considered in the clinical practice. However, there are many kinds of regimens which have different doses or different usages, including both standard FOLFOX4 2-week project validated by Evidence Based Medicine and 3- week project often used by part internal hospitals(L-OHP 130mg/m², ivgtt, 2h, the 1st day; LV 200mg/m², ivgtt, 2h, then continue 5-Fu 500mg/m², ivgtt, 4h, from the 1st day to the 5th day, and Rep every 3 weeks). Now there are few reports on the comparison of efficacy of the two projects. How to evaluate the difference and efficacy of two projects, and how to select the best regimen have become an urgent problem to be solved in clinical.Objective To search the best chemotherapy for the patients with advanced colorectal cancer to benefit the clinical treatment by observing and analyzing the clinical efficacy and side effects of the two groups with different administration (including L-OHP,5-Fu and LV).Materials and methods1 Research objectiveThere were 102 outpatients and inpatients with advanced colorectal cancer(III-IV) in the Tumor Hospital of Henan from January 2001 to December 2005 in this study , and all cases were confirmed by pathohistology with at least one measurable tumor. KPS≥70,the expected survival > 3 months, including 72 males and 30 females, with an average age of 52 years old(range36-72). AH cases were divided into group A (52 patients, with FOLFOX4 regimen) and group B (50 patients with 3-week regimen(L-OHP+5-Fu+LV)). In group A, there were 40 males and 12 females; 33 cases of rectal cancer, 19 cases of colon carcinoma; 24 cases with metastasis to liver, 12 cases to lung, 8 cases to other place; 46 cases of palliative operation or recurrent, 6 cases of nonoperation. In group B, there were 30 males and 20 females; 32 cases of rectal cancer, 18 cases of colon carcinoma; 22 cases of metastasis to liver, 10 cases to lung, 8 cases to other place; 45 cases of palliative operation or recurrent, nonoperation 5 cases. There was no significant deviation between the two groups test by chi square test (P>0.05).2 ManagementGroup A: L-OHP 85mg/m², ivgtt, 2h, d,; LV 200mg/m², ivgtt, 2h, d₁ d₂; and then 5-Fu 400mg/m², ivgtt, 2h, d₁ d₂, repeated every 2 weeks and at least 6 cycles. Group B: L-OHP 130mg/m², ivgtt, 2h, d₁; LV 200mg/m²,ivgtt, 2h, and then 5-Fu 500mg/m², ivgtt, 6h, from the d₁-d₅ day, repeated every 3 weeks and at least 4 cycles. Both of the two groups were applied preventively the receptor antagonist of 5-HT3 to prevent vomiting before chemotherapy.3 Evaluation of efficacy All the patients' liver function, renal function, blood routine examination and pectoral X-ray or CT, abdominal B-ultrasound or CT MRI were performed. In groupA, every efficacy was evaluated after 6 cycles,and in groupB, after 4 cycles. According to the efficacy evaluation criterion of solid tumor established by WHO in 1981, the efficacy was divided into 4 degrees: complete remission(CR), partial remission(PR), Stabilization(SD) and progression(PD), and the total efficacy was CR+PR.4 Toxicity and Side effectsAccording to evaluation standard of toxicity and side effects of anticancer drugs established by WHO, the toxicity and side effects were divided into four degrees (I -IV). According to L-OHP, the special classification standard, the toxicity and side effects of the nervous system were defined.5 Statistical methodSPSS 10.0 was applied, adopting t test x² test and sum of ranks test, test standard (α= 0.05).Results1 Short-term efficacyThe efficacy of 52 cases of group A: 6 cases of CR, 18 cases of PR, and the overall efficacy (CR+PR) was 46.2%. The efficacy of 50 cases of group B: 3 cases of CR, 10 cases of PR ,and the overall efficacy (CR+PR) was 26.0%. There was statistical significance between the two groups (P=0.034).2 Toxicity and Side effects2.1 Toxicity in hematological systemMyelosuppression was observed in both groups. The main manifestation was hypolekocytosis hemoglobin and thrombocytopenia decreasing, most of which was below II degree. There was no statistical significance between the two groups ( P> 0.05).2.2 Toxicity effect in gastrointestinal tractGastrointestinal response, including mainly nausea and vomit, existing in the two group patients was slight, and below II degree. There was no significant difference between two groups (P>0.05).2.3 NeurotoxicityNeurotoxicity was more frequent, and the main symptoms were sensitive to cold, numbness and pain at the end of limbs and dysesthesia, and the degree of these neurotoxicities were mild and were mainly I - II .The symptoms could recover by if treatment stopped and no adverse effect to the treatment. There was no significant difference between two groups (P>0.05).2.4 Other adverse effectsMild alopecia mucositis and increasing aminotrans- ferase observed in both groups. ECG and renal function had no obviously change in both groups.3 Median survival of the two groupsThe follow-up showed that at the beginning of chemotherapy, the medium survival of group A was 17.6 months, while 12.9 months in group B, and the median progression free time of group A was 11.2 months, while, 5.8 months in group B. There was statistical significance between the two groups (P<0.05).ConclusionThe efficacy of the advanced colorectal cancer patients receiving the FOLFOX4 two-week project is better than that of the three-week project. The former can increase the efficiency, prolong medium survival and improve the surviving ratio. The patients could tolerate while there are no difference between the two projects on toxicity and side effects. In short, the standard two-week project is safe and effective for advanced colorectal cancer patients, so it should be recommended.