Abstract Objective To observe the clinical efficacy and tolerability of oxaliplatin (L OHP) combined with fluorouracil (5 Fu), leucovorin (LV) as first-line treatment of advanced colorectal cancer. Methods 23 patients with advanced colorectal cancer, including 11 cases of colon cancer, rectal cancer 12 cases, initial treatment in 8 cases, 15 cases of retreatment, before chemotherapy were confirmed by the cubital vein indwelling intravenous catheter. L OHP 65 mg/m2, intravenous infusion 4 h, d1; LV 200 mg/m2 intravenous infusion of 2 h, 5 Fu 0.5 g/m2 CF static point after intravenous injection, continued to 5 Fu 2.4 ~ 3.0 g/m2 continuous intravenous infusion for 48 h, and 21 days for 1 cycle, the evaluation of the efficacy of once every 2 cycles. Evaluate the efficacy and toxicity according to WHO criteria. Results All patients obtained CR 2, PR 9 cases, the response rate (CR + PR) 47.8% the initial treatment effective rate of 62.5%, the retreatment rate was 45.4%, the difference was not statistically significant (P> 0.05). The main toxicities were nausea, vomiting (74%), oral mucositis and diarrhea 59.2%, and a transient peripheral nerve abnormalities 55.6%. 5 Fu Conclusion Oxaliplatin combined / LV regimen in the treatment of advanced colorectal cancer has a high efficiency, well tolerated, and adverse reactions, worthy of promotion.
Key words】 oxaliplatin; fluorouracil; leucovorin; combination chemotherapy; advanced colorectal cancer
Oxaliplatin Combined with 5 flurouracil, Leucoverini Regimen for Patients with Advanced Colorectal Cancer
SUN Shu juan1, SONG Yin li2
Tumor Heilongjiang Province Daqing People’s Hospital tumor branch Harbin Medical college Daqing school district pathology department, Daqing163316, ChinaAbstract: Objective The goal observation oxalic acid platinum (L OHP) unites the fluorine uracil (5 Fu), aldehyde hydrogen folic acid (LV) to take a plan treatment later period colon cancer the clinical curative effect and the tolerance.Methods 23 example later period colon cancer, the colon cancer 11 examples, the Rectal Cancer 12 examples, initially govern 8 examples, duplicate governs 15 examples, before the chemotherapy , passes through the elbow median vein leaving alone vein leaving alone needle. L OHP65 mg/m2, the vein drop pours for 4 hours, d1; The LV200 mg/m2 vein drop pours for 2 hours, 5 Fu0.5 g / m2 pushes the note after the CF dead center vein, continues continues the vein drop by 5 Fu2.4 ~ 3.0g/m2 to pour for 48 hours, 21 days are 1 cycle, are used together 2 cyclical appraisal curative effect. According to WHO standard appraisal in the near future curative effect and poisonous side reaction. Results The entire group patients obtain the CR2 example, the PR9 example, effectiveness (CR + PR) 47.8%, initially governs effectiveness is 62.5%, duplicate governs effectiveness is 45.4% 0.05). Main poisonous side reaction for disgusting, vomit (74%), oral cavity mycodermatitis and diarrhea 59.2%, as well as a nerve ending exceptionally 55.6%.Conclusion The oxalic acid platinum unites the">, statistics processing not obvious difference (P> 0.05). Main poisonous side reaction for disgusting, vomit (74%), oral cavity mycodermatitis and diarrhea 59.2%, as well as a nerve ending exceptionally 55.6%. Conclusion The oxalic acid platinum unites the 5 Fu / LV plan treatment later period colon cancer effectiveness to be high, the tolerance is good, the untoward effect is light, is worth the clinical promotion.
Key words: Oxalipatin; 5 Fluoracil; Leucoverini; Combination chemotherapy; Advanced colorectal cancer
Advanced colorectal cancer is one of the most common gastrointestinal malignancy, morbidity and mortality in both common malignant tumors in China 5. Due to the low rate of early diagnosis, most patients diagnosed with advanced stage, surgical removal of fewer opportunities, coupled with postoperative recurrence, the majority of patients rely on medical treatment, therefore, important chemotherapy for patients with advanced colorectal cancer. In recent years, the emergence of new treatments and new anticancer drugs, the clinical efficacy of chemotherapy for advanced colorectal cancer and tolerability has made considerable progress . Oxaliplatin is a third-generation platinum-based anti-cancer drugs listed after cisplatin and carboplatin, with high anti-cancer activity, a broad spectrum of anti-tumor, no cross-resistance with cisplatin, adverse reactions, in vitro and in vivo Clinical studies have shown that oxaliplatin significant inhibition of gastrointestinal tumors. Our hospital in January 2004 to January 2006, oxaliplatin (L OHP), fluorouracil (5 Fu), leucovorin (LV) in the treatment of 23 patients with advanced colorectal cancer, and significantly improve the quality of life of patients achieved good results in the report are as follows.
1 Materials and Methods
1.1 General Information 15 males and 8 females, aged 40 to 68 years, mean age 56 years; pathology are clearly pathological types were adenocarcinoma; initial treatment eight cases, 15 cases of retreatment staging are Ⅲ, Ⅳ; Karnofsky (KPS) score> 60, the expected survival of> 3 months, all patients had objective measurement lesions, liver and kidney function, normal ECG, no chemotherapy contraindications.
1.2 Treatment of L OHP 65 mg/m2 +5% sugar grapes 500 ml continuous intravenous infusion for 4 h, d1; LV 200 mg/m2 intravenous infusion of 2 h, 0.5 g in CF static point 5 Fu Immediately after the intravenous bolus continued to 5 Fu 2.0 g/m2 continuous intravenous infusion of 48 h, using intravenous catheter infusion pump infusion every 21 days, and at least two cycles. Before chemotherapy, the conventional application ondansetron antiemetic the hepatoprotective drug treatment, WBC <2.0 × 109, with a set of drop-stimulating factor support, 2-cycle assessment of efficacy.
1.3 Evaluation Criteria unified efficacy standards developed by the WHO, the term effect is divided into complete remission (CR), partial remission (PR), stable (SD), progress (PD), efficiency (RR) = CR + PR. 0 ~ Ⅳ toxicity according to WHO standards. Remission: time to begin to evaluate the efficacy to tumor recurrence or progression. The survival time from the start of chemotherapy to death or last followed up. KPS scores before and after treatment: After treatment, an increase of 20 divided into effective, an increase of 10 to improve, no increased stability, reduced to diminish. Significant improvement + improvement = improvement rates, and follow-up cut-off date of January 2007.
1.4 statistical methods used for SPSS10.0 statistical software processing.
2.1 Clinical efficacy of all patients evaluable for efficacy, treatment after CR 2 cases, PR in 14 cases (including six cases of colon cancer, rectal cancer cases), the total efficiency of 47.8%, SD 6 cases (26.08%), PD 6 Li (26.08%), are shown in Table 1. Table 1 L OHP combined with 5 Fu / LV regimen in the treatment of advanced colorectal cancer efficacy analysis
2.2 toxicity bone marrow suppression lighter, mainly neutropenia, the incidence rate of 17.4% (4/23), including four cases of grade Ⅰ ~ Ⅱ, Ⅲ degree 0 cases, oral mucositis incidence rate of 30.43% (7/23) were Ⅰ / Ⅱ degree. Gastrointestinal reactions are nausea, vomiting, an incidence of 34.7% (8/23), I / II degree seven cases, Ⅲ degree one cases, the incidence of diarrhea was 26.08% (6/23) are Ⅰ / Ⅱ degree, unique toxicity induced peripheral neurotoxicity of oxaliplatin, an incidence of 39.1% (9/23), manifested as numbness sensitive to cold stimuli and found no hand-foot syndrome, liver and kidney damage, as shown in Table 2 . Table 2 L OHP joint 5 Fu / LV regimen in the treatment of advanced colorectal cancer toxicity
Over the years advanced gastrointestinal cancer chemotherapy stuck 5 Fu biochemical modulator mode, 5-Fu major role in the S phase of the cell cycle (DNA synthesis phase), in recent years, scholars have found 5 Fu to the tumor cells. time-dependent, FdUMP and FUTP are respectively demonstrated cell cycle typical dynamic characteristics of non-specific and cell cycle-specific drugs, short time work mainly the FUTP role of RNA, long continuous role is FdUMP DNA direct action, and the latter is low concentrations 5 Fu sufficient. Long continuous perfusion phase can extend the drug concentration, cancer cells into the 5 Fu-sensitive S phase destruction, so that part of the original 5 Fu sensitive tumor cells become sensitive. Representatives treatment program for a new generation of 5 Fu derivatives Xeloda in combination with oxaliplatin (XELOX program) as a first-line treatment of advanced colorectal cancer. High efficacy of the program, the security is good, the side effects can be tolerated [2,3] and, on this basis, we have 5 Fu / leucovorin oxaliplatin (L OHP / 5 Fu / LV) program as first-line the treatment of advanced colorectal cancer, and to evaluate the clinical efficacy and tolerability.
Oxaliplatin is a third-generation platinum-based chemotherapy drug, using DNA as a target, the same mechanism of cisplatin, the platinum atoms with DNA to form cross-chain chain, chain crosslinking and protein cross-linking, the DNA damage and DNA binding rate 10 times faster than cisplatin. OXA broader anticancer effects than cisplatin, used in combination with 5 Fu synergistic anticancer effects. Adverse reactions, mild bone marrow suppression, renal toxicity, does not require hydration, nausea, vomiting, low incidence does not produce cardiac toxicity and severe hearing impairment. Highlight the adverse reaction of oxaliplatin is peripheral peripheral neurotoxicity, aggravated with the cumulative dose increase, the cumulative amount of 780 ~ 850 mg/m2, the dysfunction of 10% to 15%, but generally was reversible, in the withdrawal of 12 gradually restored to 13 weeks. The group containing of L OHP program main toxicities were nausea, vomiting, diarrhea, oral mucositis, neutropenia and nerve paresthesia, but multi-grade Ⅰ ~ Ⅱ by symptomatic treatment after recovery. 5 Fu biochemical modulation is today recognized synergistic clinical, biochemical regulator, but the most widely used, the mechanism more clearly LV , LV enhanced 5 Fu mechanism of anticancer activity in vivo metabolic reduction tetrahydrofolate, improve the stability of the ternary complex, to increase 5 Fu inhibition of the TS.
L OHP in recent years, with 5 Fu / LV combination therapy of colorectal cancer increasing number of foreign II, Phase III clinical studies have shown that L OHP +5 Fu / LV combination therapy of colorectal cancer was 29% to 67% of this group to treat 19 patients with advanced colorectal cancer, 9 cases of partial remission, an effective rate of 47.3%, higher than the above report, and 5 Fu 48 h infusion significantly increased efficacy related.
Colorectal cancer is relatively sensitive to chemotherapy gastrointestinal tumors, foreign reports, L OHP + LV / 5 Fu treatment of advanced or metastatic gastric cancer, objective response rate of 26% to 50%, including 4% complete remission. Domestic Jin Mao Lin et al  reported that the treatment of advanced gastric cancer remission rate of 42.5%. The group treatment of advanced colorectal cancer in 23 cases, 11 cases of partial remission rate was 47.8%, similar to the results reported at home and abroad. Prompted L OHP + LV / 5 Fu equally effective for advanced colorectal cancer. In this paper, the above method of treatment of 23 patients with advanced colorectal cancer patients, the total effective rate of 47.8%, with domestic and international the XELOX program reported close. The whole group after the treatment of 15 cases of retreatment cases applying the method still 40% efficiency, suggesting that this program is still effective chemotherapy patients. The results of this study show that the program main toxicities grade Ⅰ ~ Ⅱ gastrointestinal reactions, mild bone marrow suppression and peripheral neuropathy, no significant liver damage, and hand-foot syndrome occurred.
In summary, the of L OHP / 5-FU / LV program as a first-line treatment of advanced junction cancer efficacy, safety, side effects can be tolerated, patient compliance is good and worthy of further promotion.