Clinical Study of Combining Chemotherapy of Oxaliplatin or 5-Fluorouracil/Leucovorin with Hydroxycamptothecine for Advanced Colorectal Cancer

OBJECTIVE To estimate the short-time efficacy, side effects, survival rate after the treatment of combining chemotherapy of oxaliplatin or 5-fluorouracil/leucovorin with hydroxycamptothecine (HCPT) for the patients with advanced colorectal cancer.METHODS From January 2002 to November 2005, 59 patients with advanced colorectal cancer confirmed by pathology were enrolled into this study in the department of medical oncology,in the Sixth People's Hospital of Shanghai Jiaotong University,Shanghai. Patients' characteristics in two groups were similarly confirmed by statistic. All 37 patients in OH group received oxaliplatin (130 mg/m2 dl) plus hydroxycamptothecine (6mg/m2 d1-4), and all 22 patients in the HLF group received hydroxycamptothecine (6 mg/m2 d1-4) plus leucovorin (300 mg d1-5) and 5-fluorouracil (0.375 g/m2 d1-5). The regimens in both groups were 21-day cycle that was repeated three weeks. The side effects were evaluated. The efficacy was estimated after two cycles of chemotherapy for each patient.RESULTS The efficacy of the treatment in the OH group with 37 patients and in the HLF group with 22 patients was estimated.The overall response rate (CR + PR) was 32.4% in the OH group and 22.7% in the HLF group. There was no complete response (CR) and there was no statistical significantly difference (x2= 0.876,P = 0.704) in two groups. The 1-year survival rate was 30.98%in the OH group and 15.02% in the HLF group, and it had no significant difference between the two groups. The median PSF and OS were 5.83 months and 11.17 months in the OH group vs.7.40 months and 10.48 months in the HLF group, and it had no significant differences between the two groups (P > 0.05). The major side effects of grade Ⅲ and Ⅳ in the two groups were myelosuppression and gastrointestinal reactions. The statistically significant difference in side effects appeared in leukoperda (x2=17.173, P = 0.001), nausea/vomiting (x2 = 6.426, P = 0.039), diarrhea (x2 = 16.245, P = 0.000) and peripheral neuropathy.CONCLUSION The efficacy was almost equal between the OH and the HLF groups, and the two regimens can be used as the second-line treatments for the patients with colorectal cancer. Leucopenia, nausea, diarrhea and peripheral neuropathy appeared more in OH group, and anemia and thrombocytopenia were almost equal between the OH and the HLF groups.     

雷替曲塞联合L-OHP与5-Fu/LV联合L-OHP方案治疗晚期结直肠癌的临床疗效比较

 目的 评价雷替曲塞联合奥沙利铂（L-OHP）治疗晚期大肠癌的疗效和安全性。方法 40例晚期复治大肠癌患者分为两组,A组20例,予雷替曲塞3mg/m^2,d1,静脉注射15min,奥沙利铂130mg/m^2,d1静脉滴注3h,每3周重复1次。B组20例,奥沙利铂130mg/m^2,d1静脉滴注3h,甲酰四氢叶酸200mg/m^2,静脉滴注2h,续以5-Fu400mg/m^2静脉滴注6～8h,连用5d,每3周重复1次,每次计为1治疗周期。结果 A、B两组分别有19例和18例可评价,RR分别为36.8%和22.2%,中位TTP分别为7.8个月和5.0个月,两组结果比较差异有统计学意义（P〈0.05）。结论 雷替曲塞联合L-OHP方案在临床疗效优于5-Fu/LV联合L-OHP方案。     

大剂量醛氢叶酸加5-FU持续48小时滴注方案治疗晚期大肠癌的临床观察

目的：评价大剂量醛氢叶酸加5氟尿嘧啶（5-FU）持续48小时滴注方案治疗晚期大肠癌的客观疗效及毒副反应。方法：对入选的22例晚期大肠癌患者采用大剂量醛氢叶酸加5-FU持续48小时滴注方案进行治疗。结果：22例患者均可进行评价；平均化疗3.1个周期；CR1例，PR7例，NC11例，PD3例，总有效率为36.4%。主要的毒副反应为恶心呕吐，脱发，口腔粘膜炎，骨髓抑制及腹泻，大多为Ⅰ-Ⅱ度反应，经常规对症治疗后均见好转。结论：大剂量醛氢叶酸加5-FU持续48小时滴注为主方案治疗晚期大肠癌疗效较好。毒副反应轻。     

草酸铂联合5-氟脲嘧啶与甲酰四氢叶酸治疗晚期大肠癌临床观察

目的　观察草酸铂联合化疗治疗晚期大肠癌临床疗效。方法　 3 2例晚期大肠癌患者 ,用草酸铂 13 0mg/m2 ,静脉滴注 2小时 ,化疗d1,甲酰四氢叶酸 10 0mg/m2 化疗d1～ 5 ;5 氟脲嘧啶 0 .5g静脉滴注化疗d1～ 5 ,每 3周重复一次 ,治疗 2周期后评定疗效 ,有效病例 4周期后确认疗效。结果　 3 2例中CR 3例 ,PR 11例 ,SD 14例 ,PD 4例 ,总有效率 (CR PR) 43 .8%。主要毒副作用 :Ⅰ～Ⅱ度恶心、呕吐 ,腹泻 ,感觉神经毒性 ,黏膜炎 ,骨髓抑制 ,静脉炎等。结论　草酸铂联合 5 FU CF治疗晚期大肠癌效果良好 ,不良反应可耐受 ,值得临床推广。     

含羟基喜树碱方案联合化疗晚期大肠癌的临床观察

目的　观察 10 -羟基喜树碱 (HCPT)、甲酰四氢叶酸钙 (CF)、5 -氟脲嘧啶 (5 -Fu)联合治疗晚期大肠癌的临床疗效。方法　将5 7例晚期大肠癌随机分为两组 ,分别采用HCPT + 5 -Fu +CF方案及 5 -Fu +CF方案化疗两个周期以上 ,评定其疗效及毒性。结果　HCPT + 5 -Fu +CF组有效率 5 3 6 % ,明显高于 5 -Fu +CF组的 2 7 6 % (P <0 0 5 ) ,毒副反应较轻。结论　HCPT + 5 -Fu +CF具有协同作用 ,可以作为晚期大肠癌的首选方案。     

High and Low Dose Folinic Acid, 5-Fluorouracil Bolus and Continuous Infusion for Poor-Prognosis Patients with Advanced Colorectal Carcinoma

Objective: Evaluation and assessment of response rate, duration and toxicity in patients subjected to 5-FUbased chemotherapy. Background: The therapeutic ratio shifts with different 5FU/LV regimens and none yetserve as the internationally accepted Gold Standard . A bimonthly regimen of high dose leucovorin is reportedto be less toxic and more effective than monthly low dose regimens. We here compare therapeutic responses andsurvival benefit of the two regimens in poor prognosis patients with advanced colorectal carcinoma. Patients andMethods: A total of 35 patients with histologically confirmed colorectal carcinoma were subjected to de Gramontand Mayo Clinic regimen. Nineteen patients were treated with high dose folinic acid (200 mg/m2), glucose 5%,5-FU (400 mg/m2) and 22 hr. CIV (600 mg/m2) for two consecutive days every two weeks. These patients hadfailed responses to previous chemotherapy and were above sixty years of age with poor general status. Sixteenpatients (six below 60 years) with progressive disease were subjected to low dose folinic acid (20 mg/m2)for fivedays, 5FU(425 mg/m2) injection bolus for 5 days, every five weeks. An initial evaluation was made in sixty daysand responders were reevaluated at sixty days interval or earlier in case of clinical impairment. Based on positiveprognosis, the therapy was continued. Evaluation of treatment response was made on the basis of WHO criteria.Results: The response rate was 44% in thirty four evaluable patients, with 4 complete responses (11.8%) and 11(32.4%) partial responses. The two schedules were well tolerated, whereas, mild toxicity without WHO Grade≥2 events was assessed. The response duration was extended (12 months) in a few patients with age above sixtyyears treated by high dose bimonthly regimen of 5FU/LV. Conclusion: The regimens are safe and effective inadvanced colorectal carcinoma patients with poor general status.     

Treatment of Advanced Gastric Carcinoma Patients with Calcium Folinate, a 5-Fluorouracil Bolus and Continous Infusion with 5-Infusion with 5-Fluorouracil Combined with Oxaliplatin

OBJECTIVE To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil (5-FU) bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin (L-HOP)in treating advanced gastric carcinoma patients.METHODS Sixty-five patients with advanced gastric carcinoma were treated with high-dose-folinic acid plus a 5-FU bolus and a 48-h continuous infusion of 5-FU combined with oxaliplatin. The effects of treatment and toxicity were observed.RESULTS There were 4 complete responses, 26 partial responses,30 with no change and 5 with progressive disease. The overall effective response rate was 46.2% (30/65). The median duration was 7 months, with the main side effects including nausea and vomiting, peripheral phlebitis, alopecia, leukopenia, dental ulcers,peripheral neuritis and diarrhea. All the side effects were tolerated and minimal.CONCLUSION The results showed that high-dose folinic acid plus a 5-FU bolus and continuous infusion of 5-FU combined with oxaliplatin appears to be a safe and effective therapy for patients with advanced gastric carcinoma. This therapeutic regimen is of value for these patients.     

低剂量PF方案持续注射治疗晚期肝癌的疗效观察

目的 观察低剂量PF方案持续注射治疗晚期原发性肝癌(PHC)的疗效和毒副反应.方法 70例晚期PHC随机分为两组,治疗组36例给予低剂量PF持续静脉注射方案:DDP 3 mg/(m2·d),civ,d1-5/周;CF 100 mg,civ,d1,4/周;5-Fu 170 mg/(m2·d),civ,6～8 h/d,d1-7/周,连用3周为1周期,至少完成1个周期或以上.对照组34例给予最佳支持治疗.结果 治疗组和对照组的临床症状改善(即临床受益反应)有效率分别为55.6%(20/36)、23.5%(8/34),差异有统计学意义(P<0.01),中位生存期均为17.00周,治疗组的毒副反应可以耐受.结论 低剂量PF持续静脉注射方案治疗晚期PHC,毒副反应可耐受,可以提高生存质量,但未延长生存期.     

不同方法输注氟脲嘧啶、亚叶酸钙联合奥沙利铂治疗晚期消化道肿瘤的临床研究

目的:比较氟脲嘧啶(5-FU)不同输注法联合亚叶酸钙、奥沙利铂对晚期消化道肿瘤疗效及不良反应。方法:76例晚期消化道肿瘤患者随机分成A、B2组,A组36例,5-FU采用双周疗法;B组40例,5-FU采用持续5天滴注疗法。结果:A组CR 6例(胃癌4例、大肠癌2例),PR 18例(胃癌8例、大肠癌10例),总有效率66.67％(胃癌75％、大肠癌60％)。B组CR 4例(胃癌3例、大肠癌1例),PR 12例(胃癌5例、大肠癌7例),总有效率40％(胃癌44.44％、大肠癌36.36％),二组比较有显著性差异(P<0.01)。主要副作用有:白细胞数下降、感觉神经毒性、口腔粘膜炎、腹痛及腹泻等,A、B 2组相比无显著性差异(P>0.05)。结论:5-FU双周疗法联合亚叶酸钙、奥沙利铂较持续5天滴注疗法有效率明显提高,且未增加不良反应。     

紫杉醇加5-氟脲嘧啶持续滴注治疗晚期鼻咽癌

目的：观察紫杉醇（Paclitaxel)，醛氢叶酸（Leucovorin),5-氟脲嘧啶（5－Fluorouraicl)持续滴注治疗晚期鼻咽癌的疗效及其不良好反应。方法：经病理组织学诊断的鼻咽癌患者20例（研究组），紫杉醇150mg/m^2，静脉滴注3h，第1天，醛氢叶酸200mg/m^2，静脉滴注2h，随后5－Fu375mg/m^2静脉推注10min再接5－Fu3.0g/m^2用输液泵连续滴注48h,以上治疗21天为1个周期，所有患者至少接受2个疗程治疗，结果：20例均可评价疗效，完全缓解（CR）3例（15．0％），部分缓解（PR）10例（50．0％），4例患者稳定（20．0％），主要不良反应为骨髓抑制，恶心、呕吐、肌肉疼痛和关节痛，黏膜炎等，经常规预防用药后，未出现严重的过敏反应，无治疗相关性死亡者，结论：该研究表明，紫杉醇加醛氢叶酸和5－Fu持续滴注治疗晚期鼻咽癌患者，缓解率较高，毒性相对较弱，值得进一步临床研究。     

奈达铂联合5-氟脲嘧啶治疗晚期食管癌24例

目的 :观察奈达铂联合5-氟脲嘧啶治疗晚期食管癌的疗效和不良反应。 方法 :晚期食管鳞癌患者24例,奈达铂80～100mg/m²,加入生理盐水500ml中静滴2h,5-氟脲嘧啶1.0g/天,静脉滴注4h以上,第1～5天。28天为1周期,连用2个周期后评价疗效。 结果 :全组24例均可评价疗效及不良反应,总有效率41.7%。其中初治者14例,完全缓解1例,部分缓解6例,有效率50.0%;复治者10例,部分缓解3例,有效率30.0%。中位生存时间9.4个月,1年生存率25.0%。主要不良反应为骨髓抑制,4例(16.7%)患者出现Ⅲ度血小板下降,3例(12.5%)患者出现Ⅲ～Ⅳ度白细胞降低。消化道反应轻,未发现肝肾功能损害。 结论 :奈达铂联合5-氟脲嘧啶治疗晚期食管癌疗效肯定,不良反应小,尤其对老年患者耐受性好,可代替顺铂作为治疗晚期食管癌的一线方案,对顺铂耐药的患者亦有一定的疗效。     

奥沙利铂联用氟脲嘧啶、亚叶酸钙治疗晚期大肠癌的临床研究

目的　观察奥沙利铂联用氟脲嘧啶、亚叶酸钙治疗晚期大肠癌 (ACRC)的疗效和安全性。方法　收治晚期大肠癌患者 3 0例 ,采用L_OHP 13 0mg/m2 静脉滴注 4hd1 ;CF 2 0 0mg/m2 静脉滴注半小时后 5_Fu 5 0 0mg/m2 静脉滴注 6hd1～ 5,每 3周重复。结果　部分缓解 (PR) 9例 ,稳定 (SD) 8例 ,进展 (PD) 8例 ,总有效率 3 6%。毒性反应主要为感觉神经毒性 ( 90 %) ,其次为恶心呕吐 ( 60 %)和腹泻 ( 4 6 7%)。骨髓抑制毒性小。结论　L_OHP联合 5_Fu、CF治疗大肠癌疗效肯定 ,耐受性良好 ,值得临床进一步研究     

奥沙利铂加氟脲嘧啶持续静脉滴注治疗晚期鼻咽癌

目的　观察奥沙利铂 (Oxaliplatin ,L_OHP) ,醛氢叶酸 (Leucovorin ,LV) ,氟脲嘧啶 ( 5_Fluorouracil ,5_Fu)持续静脉滴注治疗晚期鼻咽癌 (NPC)的疗效及其不良反应。方法　经病理组织学诊断的鼻咽癌患者 2 1例。L_OHP 13 0mg/m2 静脉滴注 2h ,第 1天 ;LV 2 0 0mg/m2 ,静脉滴注 2h ,随后 5_Fu 3 75mg/m2 ,静脉推注 10min ,再接 5_Fu 3 0g/m2 用输液泵连续滴注 12 0h ,以上治疗 2 1天为 1周期。所有患者至少接受 2个周期治疗。结果　 2 1例均可评价疗效 ,完全缓解 (CR) 3例 ( 14 3 %) ,部分缓解 (PR) 11例 ( 5 2 4%) ,4例患者稳定( 19 0 %) ,主要不良反应为神经毒性 ,骨髓抑制 ,恶心呕吐 ,腹泻 ,黏膜炎等。无治疗相关性死亡者。结论　该研究表明 ,L_OHP加LV和 5_Fu持续滴注治疗晚期鼻咽癌患者 ,缓解率较高 ,毒性相对较低 ,值得进一步临床研究     

替吉奥胶囊联合奥沙利铂治疗晚期结直肠癌的临床观察

目的比较奥沙利铂联合替吉奥胶囊方案及FOLFOX4方案治疗晚期结直肠癌的临床疗效及毒副反应。方法46例晚期结直肠癌患者分为2组,观察组24例应用替吉奥胶囊联合奥沙利铂化疗,28d为1周期,至少完成2周期;对照组22例应用FOLFOX4方案化疗,28d为1周期,至少完成2周期。治疗后评价临床疗效和毒副反应。结果观察组有效率为54．17％,对照组为54．55％,差异无统计学意义（P〉0．05）。观察组毒副反应发生率稍低于对照组,但差异均无统计学意义（P均〉0．05）。结论替吉奥胶囊联合奥沙利铂疗效与传统的FOLFOX4方案相近,且安全性及患者耐受性方面具有一定优势,可作为晚期结直肠癌患者的治疗方案用于临床。     

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目的 观察甲酰四氢叶酸钙(CF)联合5-氟尿嘧啶(5-Fu)治疗晚期乳腺癌的疗效和安全性.方法 选择既往经过蒽环类、紫杉类等药物治疗无效的晚期乳腺癌31例,中位年龄48.0岁(27～66岁).采用CF联合5-Fu化疗方案治疗.CF[150 mg/(m2·d)]+ 5-Fu[600 mg/(m2·d)],连用5天,每天静脉滴注不少于12h,每4周为一周期.观察有效率及不良反应.结果 完全缓解2例(6.5％),部分缓解7例(22.6％),病情稳定6例(19.4％),进展16例(51.6％).总有效率为29.0％,临床获益率为48.4％,其中激素受体阴性患者更能获益(P＜0.05).中位有效期为2.3月(95％CI:1.1～4.1),中位生存期为9.5月(95％CI:4.7～14.8).15例(48.4％)生活质量改善,6例(19.4％)稳定,10例(32.3％)下降.不良反应主要是胃肠道反应(11例)、骨髓抑制(4例)和口腔炎(9例).结论 CF+ 5-Fu联合静脉滴注二线治疗晚期乳腺癌疗效确切,不良反应可控,患者易于耐受,可以作为复发转移的晚期难治性乳腺癌的解救治疗.     

The Effect of 5-Fluorouracil on the Adhesion Process in Patients Operated on for Colorectal Cancer

Objective: The aim of this study was to improve the direct results of reconstructive surgery in patients operated on for complicated forms of colorectal cancer, by using 5-fluorouracil in the postoperative period. Methods: The study involved 126 patients (they were divided into 2 groups) with colorectal cancer, who underwent reconstructive surgery. They underwent a standard clinical examination and a mandatory examination program. Results: The use of 5-fluorouracil in adjuvant treatment in patients with colorectal cancer significantly reduces the number of subjective clinical manifestations (positional tests) in the main group – 17%, and in the control group – 54.3%, as well as objective clinical manifestations (instrumental research methods) in Group I – 13%, and Group II – 89.5%, respectively. The study shows that in re-operated patients with colorectal cancer who received 5-fluorouracil, abdominal adhesions are characterized by a low content of collagen and fibroblasts, low vascularization and a high content of polymerized fibrin strands. It was also found that re-operated patients with colorectal cancer who did not receive 5-fluorouracil, abdominal adhesions are characterized by a high collagen content, a large number of fibroblasts, and severe angiogenesis. Conclusion: It was found that the prolonged administration of 5-fluorouracil statistically significantly reduces the risk of adhesions, thereby showing the effectiveness of preventing adhesive disease of the abdominal organs. It was shown that the prolonged administration of 5-fluorouracil significantly reduces the number of subjective and objective signs of adhesive disease of the abdominal organs, as well as significantly decreases intraoperative and postoperative complications, the duration of the operation, and the amount of blood loss. In the postoperative period, it reduces the length of hospital stay and improves the quality of life of patients.     

The Emerging Role of 5-Fluorouracil and Leucovorin in the Treatment of Advanced Breast Cancer. A Review

Summary

Considerable interest has been generated by the clinical experience with 5-fluorouracil + leucovorin based regimens in colorectal cancer. Consequently, this combination was tested in other tumors in which 5-fluorouracil has some activity (gastric, pancreatic, head and neck and breast cancer).

This review summarizes the interesting results reported so far in advanced breast cancer.

Up to now, more than 300 patients have been treated with chemotherapeutic regimens based on this attempt at biochemical modulation of 5-fluorouracil's activity. Overall, a median response rate of 26% was achieved by nine studies performed in 245 mainly pretreated patients with an acceptable degree of toxicity. Moreover, two additional studies explored the clinical activity of this combination as first-line chemotherapy for advanced disease with impressive results.

Current efforts to further improve the therapeutic index of this combination will also be briefly discussed.     

A Phase II Study of Advanced Colorectal Cancer Patients Treated with Combination 5-Fluorouracil Plus Leucovorin and Subcutaneous Interleukin-2 Plus Alpha Interferon

Summary

Twenty-one patients with advanced, pretreated colorectal cancer in disease progression were entered in a phase II study to investigate the use of 5-fluorouracil (5FU) + leucovorin with subcutaneous Interleukin-2 + alpha interferon (α-IFN). Eighteen of these patients were evaluable for response to treatment: 1 partial response (PR) (duration 8 months), 9 stable disease (SD) (median duration of 6.5 months, range 2-15) and 8 progressive disease (PD). The PR patient survived for 15 months, the SD patients for a median of 11 months and 8 months for PD patients. Toxicity evaluated in the 21 patients reached grade 4 for mucositis in two cases. Grade 3 toxicity was observed more frequently for fever (52.3%) and diarrhea (33.3%) and was most probably the result of the combined side-effect of chemotherapy and the biological response modifiers (BRMs). Treatment was, for the most part, carried out on an out-patient basis as originally planned.

In 15 patients tests were carried out to verify whether any immuno-activation had taken place. Significant increases were found during the course of therapy regarding cluster of differentiation activation (HLA-DR, CD71, CS25). Different curves were observed during the course of treatment with respect to the CD8 value, which proved higher in SD patients than in PD patients.

Our study would seem to suggest that the addition of BRMs to 5FU + leucovorin could increase survival. The next step, however, must be to determine lower doses of IL-2 for subcutaneous administration in order to reduce toxicity but maintain the same immunostimulation.     

奥沙利铂联合亚叶酸钙与5-氟脲嘧啶治疗老年晚期结直肠癌的临床研究

目的评价国产奥沙利铂（L-OHP）联合亚叶酸钙（CF）、5-氟脲嘧啶（5-Fu）治疗局部晚期或转移性老年结直肠癌患者（≥70岁）的临床疗效及毒副反应。方法入组30例患者，方案L-OHP130mg／m^2静脉滴注2h，第1天；CF200mg／m^2静脉滴注2h，第1～5天；5一Fu425mg／m^2静脉滴注6h，第1-5天。每3周重复，两周期后评价疗效。结果30例患者均可评价疗效，无CR病例，PR15例，SD8例，PD7例，有效率为50％，中位生存期18个月，中位无进展生存9．5个月，1年生存率为66.7％。主要毒副反应为神经毒性，中性粒细胞减少，消化道反应及腹泻。结论L-OHP联合5-Fu／FA方案治疗局部晚期或转移性老年结直肠癌患者疗效较高，耐受性较好，值得进一步研究。