伊立替康联合5-FU/CF治疗转移性结直肠癌46例

目的：评价伊立替康（CPT—11）联合5-FU／CF方案治疗FOLFOX4或LV5FU2方案失败的结直肠癌的客观疗效，临床受益和不良反应。方法：用CPT—11联合5-FU／CF方案治疗晚期结直肠癌患者46例，采用2周方案，即CPT—11 180mg／m^2 iv d1，CF200mg／m^2 iv d1-2，5-FU400mg iv bolusd1，5-FU600mg／m^2 iv，22hd1—2，每2周重复。观察期3—6个月。结果：完全缓解0例，部分缓解18例（有效率39．13％），稳定20例（43．47％），进展8例（17．39％）。临床受益率82．6％（19／23）。临床反应评价有效者36例（78．86％），生活质量显著提高。结论：CPT-11联合5-Fu／CF方案可作为转移性结直肠癌的二线治疗。     

5-fluorouracil as a protracted continuous infusion plus irinotecan (CPT-11) in patients with advanced colorectal cancer treated with fluoropyrimidine-based regimens as first line

We carried out a single-center series with the combination of irinotecan (CPT-11) plus protracted 5-fluorouracil (5-FU) infusion as second-line chemotherapy for patients previously treated with a single-agent fluoropyrimidine as monotherapy or in combination with oxaliplatin. Twenty-five patients diagnosed with advanced colorectal cancer (CRC) received CPT-11 300 mg/m2 every 3 weeks plus 5-FU 250 mg/m2/day as a protracted infusion. Results were as follows. Twenty-four of 25 patients were evaluable for response. Two patients achieved a complete response and five a partial response, resulting in an overall response rate of 28%. Disease stabilization was obtained in 10 patients (40%), resulting in a tumor growth control rate of 68% (17 patients) and disease progression in seven (28%). Median progression-free interval was 6 months and median overall survival was 12 months. Neutropenia and diarrhea appeared as the most frequent adverse events, being grade 3/4 in 12 and 16% of patients, respectively. Mucositis, emesis, and hand and foot syndrome were mild. We conclude that protracted 5-FU infusion plus CPT-11 is an active and safe regimen for patients with advanced CRC. A phase III trial comparing this schedule with conventional CPT-11 monotherapy is warranted.     

伊立替康联合氟尿嘧啶/亚叶酸钙治疗转移性结直肠癌

目的观察伊立替康联合亚叶酸钙及氟尿嘧啶方案治疗FOLFOX4方案失败的晚期结直肠癌的临床疗效及毒副反应。方法用CPT-11联合5-FU/CF方案治疗晚期结直肠癌患者28例,采用2周方案化疗,至少2个周期,即CPT-11180mg/m2静脉滴注,第1天;四氢叶酸200mg/m2静脉滴注,第1、2天;5-FU400mg/m2静脉推注,第1、2天;5-FU600mg/m2静脉滴注22h,第1、2天。按照WHO实体瘤近期客观疗效评定标准进行评价。结果全组28例患者均可评价疗效及不良反应。其中完全缓解0例,部分缓解10例,稳定9例,进展9例,有效率为35.7%。中位肿瘤进展时间TTP6.5个月,中位生存时间MST为12.5个月。不良反应主要是骨髓抑制,恶心、呕吐,脱发及延迟性腹泻。结论伊立替康联合5-FU/CF为二线治疗晚期结直肠癌安全有效的方案。     

Dramatic tumor response of bulky liver metastases following treatment with CPT-11 and a chronomodulated 4-day infusion of 5-fluorouracil, folinic acid and oxaliplatin every 2 weeks in a colorectal cancer patient

Three active antitumor agents, i.e. 5-fluorouracil (5-FU), oxaliplatin and CPT-11, are available for the treatment of advanced colorectal cancer (CRC) patients and have been successfully combined in two-drug regimens. Hence, CRC has become a chemosensitive disease, but the optimal combination of these agents in first-line treatment remains to be determined. We report the first case of the combination of CPT-11 with oxaliplatin, 5-FU and folinic acid (FA) as first-line chemotherapy for a patient with a pre-occlusive sigmoid adenocarcinoma and synchronous bulky liver metastases. CPT-11 was given at 125 mg/m2, prior to the start of a chronomodulated 4-day infusion of oxaliplatin 25 mg/m2/day, 5-FU 800 mg/m2/day and FA 300 mg/m2/day repeated every 2 weeks. The doses could be escalated to 150 mg/m2 for CPT-11 and 900 mg/m2/day for 5-FU. After six cycles of chemotherapy 70% reduction in tumor size was documented in the liver. The primary tumor was no longer detectable by barium enema. The toxicity included three episodes of grade 4 neutropenic fever, and two episodes of severe diarrhea and vomiting with dehydration. A cumulative grade 2 neurosensory toxicity was observed after six cycles. Following surgery of the primary tumor, because of the major hepatic tumor response and of the absence of extra-hepatic metastases, the patient might be registered for a liver transplantation program. This first report of combining the three active agents in CRC every 2 weeks led to a high dose intensity of each agent and was associated with a dramatic tumor response of a very advanced disease in a patient with already altered performance status. The antitumor activity in this patient suggests that a three-drug intensified regimen might be feasible and active. A prospective study appears warranted to further examine the efficacy and toxicity of this therapeutic approach, and to determine whether it may increase the fraction of advanced CRC patients becoming resectable. This aggressive chemotherapy program may contribute to a re-examination of the usefulness of liver transplantation in patients with metastatic CRC confined to the liver.     

Adding weekly irinotecan to high-dose 5-fluorouracil and folinic acid (HD-5-FU/FA) after failure for first-line HD-5-FU/FA in advanced colorectal cancer--a phase II study

Irinotecan (CPT-11) has been shown to prolong survival and improve quality of life in comparison to best supportive care in colorectal cancer patients with pretreatment of bolus 5-fluorouracil (5-FU). After first-line 24-h high-dose (HD) 5-FU/folinic acid (FA) an objective response rate of 11% with 3-weekly CPT-11 350 mg/m was reported. In the present study we investigated weekly CPT-11 in combination with 24-h HD-5-FU/FA as second-line treatment after prior exposure to 24-h HD-5-FU. Synergy between 5-FU and CPT-11 is the rationale to combine both substances for second-line therapy in order to overcome resistance to 5-FU. Thirty-five patients were recruited in a single institution to receive 6 x weekly CPT-11 80 mg/m(2), FA 200 mg/m(2) and 24-h HD-5-FU 2000 mg/m(2). Treatment was repeated on day 57. Patient characteristics: M/F=20/15, median WHO performance status 1, range (0-2). Thirty-four patients were evaluable for response: partial response 17% and no change 40%. Median time to progression and overall survival were 3.3 and 8.4 months, respectively. All patients were evaluable for toxicity analysis (National Cancer Institute Common Toxicity Criteria grade 3): leukocytopenia 3%, diarrhea 12% and vomiting/nausea 6%. Of the assigned doses, a median 100% of 5-FU and 92% of CPT-11 were administered during the first cycle of chemotherapy. We conclude that weekly CPT-11 and HD-5-FU/FA is an active and safe combination chemotherapy resulting in response rates in the upper range of other CPT-11-based second-line regimen. The toxicity profile in our series compared to 3-weekly CPT-11 seems favorable.     

Phase I study of the combination of oxaliplatin, irinotecan and continuous infusion 5-fluorouracil in digestive tumors

Oxaliplatin (L-OHP), irinotecan (CPT-11) and 5-fluorouracil (5-FU) have shown their efficacy in metastatic colorectal cancer. The synergism of these drugs has been demonstrated in vivo and in vitro. The aim of this study was to determine the recommended dose of the triple combination of L-OHP, CPT-11 and CI 5-FU for a further phase II study. Eighteen patients received the study treatment in four dose levels. The male:female ratio was 15:3 and the median age was 51.6 years (range 30-71). The type of tumor was colon in eight patients, rectum in four and other locations in six patients. The treatment was repeated every 2 weeks, at the fixed dose of L-OHP, 85 mg/m, and escalated doses of CPT-11 and 48-h infusion 5-FU of 100/2000, 100/2250, 125/2250 and 150/2250 mg/m. Only one previous treatment for the advanced disease was permitted. Patients received a median of 8 cycles (range 1-26) and a total of 152 cycles were administered. Dose intensity administered at dose level L-OHP 85 mg/m, CPT-11 150 mg/m and 5-FU 2250 mg/m was 95, 92 and 95% for L-OHP, CPT-11 and 5-FU, respectively. One patient in level 2 and one patient in level 4 presented dose-limiting toxicity that was not confirmed in the three required additional patients by level. The anti-tumor activity was assessed in nine patients: seven partial responses, one stable disease and one progressive disease. The maximum-tolerated dose was not reached, and thus the recommended dose for this combination schedule is L-OHP, 85 mg/m, CPT-11, 150 mg/m and 5-FU, 2250 mg/m 48-h continuous infusion, the same doses that were recommended for the drugs when administered in combination therapy of L-OHP + 5-FU or CPT-11 + 5-FU. A phase II study in first-line treatment of patients with metastatic colorectal cancer with this dose regimen is ongoing.     

伊立替康联合草酸铂、5-氟尿嘧啶、亚叶酸钙治疗晚期胃癌的临床疗效

目的:比较伊立替康联合奥沙利铂和5-氟尿嘧啶、亚叶酸钙(FOLFOXIRI)与奥沙利铂联合CF,5-FU(FOLFOX4)治疗进展期或转移性胃癌的疗效和毒副反应。方法:经病理确诊的进展期或转移性胃癌患者78人,随机分为两组,FOLFOXIRI组36人,FOLFOX6组42人。FOLFOX4方案:L-OHP 85 mg/m2,第1天静滴,CF 200 mg/m2,5-FU 400 mg/m2,静冲,5-FU 600mg/m2,第1,2天,持续静点22h。FOLFOXIRI方案用法:CPT-11 165 mg/m2,L-OHP,CF,5-FU用法同FOLFOX4。结果:FOL-FOXIRI方案与FOLFOX4方案一线治疗进展期或转移性胃癌的缓解率分别为53.07%和28.57%(P=0.028),中位生存期分别为11.8月和9.4月(P=0.321),中位疾病进展时间为6.0月和4.8月(P=0.036)。FOLFOXIRI方案的骨髓毒性和腹泻发生率高于FOLFOX4方案。结论:本研究结果显示FOLFOXIRI方案治疗胃癌近期缓解率高于FOLFOX4方案,不良反应可以耐受,值得更深入系统地进行临床研究。     

伊立替康联合氟尿嘧啶二线治疗晚期结直肠癌观察

目的:观察伊立替康(CPT-11)联合氟尿嘧啶治疗一线化疗失败的晚期结直肠癌的疗效.方法:61例晚期结直肠癌患者,均为经奥沙利铂、氟尿嘧啶、亚叶酸钙等药物一线化疗失败者,行伊立替康联合氟尿嘧啶方案治疗,第1天伊立替康180 mg/m2静脉滴注90 min,第1天、第2天亚叶酸钙200 mg/m2静脉滴注,第1天、第2天...     

Irinotecan (CPT-11) in metastatic colorectal cancer patients resistant to 5-fluorouracil (5-FU): a phase II study

The efficacy and toxicity of irinotecan (CPT-11) 350 mg/m(2) i.v. once every 3 weeks was assessed in 60 patients with advanced colorectal cancer (CRC) showing failure to 5-fluorouracil (5-FU) treatment. The overall objective response rate was 13.6% (1 complete response and 4 partial responses) and 25 patients (42.4%) showed stable disease; the median time to disease progression was 4.4 months and the median survival was 10.5 months. The main non-hematological toxicities were alopecia (80.3% of patients), diarrhea (75.0%), and nausea/vomiting (71.7%); neutropenia was the main hematological toxicity. Grade 3 or 4 diarrhea appeared in 21 of 131 cycles (16.1%), whereas grade 3 or 4 neutropenia appeared in 78 cycles (25.0%). In conclusion, the present phase II study confirms that CPT-11 350 mg/m(2) every 3 weeks is active and well tolerated as second-line chemotherapy for CRC in 5-FU resistant patients.     

开普拓5-FU/CF治疗晚期结直肠癌临床观察

目的观察CPT-11(开普拓)联合5-FU/CF治疗晚期结直肠癌的临床疗效和毒副反应。方法入组患者27例均为手术后局部复发和转移的晚期结直肠癌,经FOLFIRI方案化疗二个疗程(共4次)后,评价疗效,按照WHO实体瘤近期客观疗效评定标准进行评价。结果全组27例均可评价疗效及不良反应。完全缓解(CR)为0,部分缓解(PR)为6例(6/27),总有效率(CR+PR)达22%,疾病稳定(SD)16例(16/27)59.26%,疾病控制率(CR+PR+SD)为81.48%,疾病进展(PD)5例(5/27)18.52%。中位疾病进展时间为7.1个月(5～26个月),中位生存时间9.2个月。不良反应主要是消化道反应和骨髓抑制,以延迟性腹泻为多见,有8例为Ⅰ/Ⅱ度,Ⅲ/Ⅳ度仅1例,有4例Ⅰ/Ⅱ度骨髓抑制,Ⅲ/Ⅳ度骨髓抑制仅2例,无治疗相关的死亡。结论开普拓联合5-FU/CF治疗晚期结直肠癌近期疗效确切,不良反应可控制,临床上可大胆应用。     

Oxaliplatin and 5-fluorouracil for heavily pretreated metastatic breast cancer: a preliminary phase II study

Oxaliplatin shows in vitro and in vivo synergism with 5-fluorouracil (5-FU). In this study we evaluate the clinical efficacy of oxaliplatin and 5-FU in heavily pretreated metastatic breast cancer. Eligible patients had to be pretreated with both anthracyclines and taxanes. Pretreatment with capecitabine was recommended but not mandatory. Chemotherapy: oxaliplatin 85 mg/m2/2 h day 1, folinic acid 400 mg/m2/2 h day 1, 5-FU 400 mg/m2 i.v. push day 1, 5-FU 2400 mg/m2 continuous infusion/48 h day 1, q2w. Fourteen patients were included: one male and 13 females; age: median 53 years (38-62); ECOG 0: three patients, 1: nine patients, 2: two patients; all patients were pretreated with anthracyclines and taxanes, capecitabine: nine patients, vinorelbine: six patients, trastuzumab: four patients, hormonal therapy: 12 patients; lines of prior palliative chemotherapy: 0: one patient, 1: three patients, 2: one patient, 3: three patients, 4: four patients, 5: two patients. Results: median number of cycles: 8 (range 1-17). Toxicity (14 patients evaluable; no. of patients with Common Toxicity Criteria grade 3/4): asthenia: 2/-, paraesthesia 3/-, leuko/neutropenia: 1/2, no neutropenic fever, other (alopecia, skin): 2/-. Response (12 patients evaluable, all with bidimensionally measurable disease): complete remission: no patients, partial remission: four patients (33%, all confirmed), stable disease: five patients, progressive disease: three patients. We conclude that despite the small number of patients, the combination of 5-FU and oxaliplatin shows promising efficacy in this heavily pretreated population.     

Prospective multicenter phase II study of irinotecan as third-line therapy in metastatic colorectal cancer and progression after bolus and infusional 5-fluorouracil

Irinotecan has proven anti-tumor activity as induction treatment in combination with 5-fluorouracil (5-FU) or as second-line treatment after 5-FU in patients with metastatic colorectal cancer. The aim of the present phase II study was to evaluate irinotecan as third-line chemotherapy in patients with colorectal cancer after sequential treatment with bolus 5-FU followed by an infusional 5-FU regimen. Patients pretreated with bolus 5-FU/folinic acid and the infusional 5-FU/folinic acid regimen were treated with 350 mg/m irinotecan i.v. once every 3 weeks in a multicenter phase II study. Tumor size was measured every cycle and treatment with irinotecan was continued until the occurrence of progressive disease or unacceptable toxicity. A total of 50 pretreated patients were included. Of the 45 evaluable patients, 13.3% [n=6, 95% confidence interval (CI) 5.1-26.8] attained a response (complete/partial response) to treatment lasting 5.6 months (95% CI 4.2-6.3) and in four patients response has been confirmed (8.9%, 95% CI 2.5-21.2). Disease stabilization was noted in 51.1% of the patients (n=23, 95% CI 35.8-66.3). The median duration of response/disease stabilization was 4.2 months (95% CI 3.2-6.0). Median overall survival was 7.9 months (95% CI 6.1-11.1), corresponding to a calculated 1-year survival of 28.3% (95% CI 15.2-41.3). Severe neutropenia occurred in 14% (n=7) and anemia grade III in 6% of the patients (n=3). The most frequent non-hematological toxicity grade III/IV related to treatment was diarrhea in 24% of the patients (n=12), followed by vomiting in 8% (n=4) and constipation as well as infection in two patients each (4%) (evaluable n=50). We conclude single-agent irinotecan is an effective and well-tolerable treatment in pretreated patients with metastatic colorectal cancer after failure of bolus and infusional 5-FU/folinic acid regimens. Elderly patients had the same probability to respond.     

Oxaliplatin: a review of its use in combination therapy for advanced metastatic colorectal cancer

Oxaliplatin (Eloxatin) is the only platinum compound to show clinical activity in colorectal cancer. The efficacy of a combination of oxaliplatin with various schedules of fluorouracil (5-FU)/folinic acid (FA) as first- or second-line treatment for advanced metastatic colorectal cancer has been investigated in large phase III trials. FOLFOX4 (an oxaliplatin/5-FU/FA regimen) as first-line therapy (n = 795) was superior to irinotecan/5-FU/FA (IFL). Response rates were 45% vs 31%, and median progression-free survival duration was 8.7 vs 6.9 months. The survival advantage shown by FOLFOX4 over the irinotecan combination (median survival duration 19.5 vs 14.8 months) may be confounded by differences in post-study treatment but equivalent efficacy is supported by another phase III trial of oxaliplatin and irinotecan combinations. As first-line therapy, oxaliplatin added to various 5-FU/FA regimens more than doubled the response rates from 16-22.6% to 48.3-53% and the median duration of progression-free survival was significantly longer with oxaliplatin/5-FU/FA than 5-FU/FA alone (7.9-9 versus 5.3-6.2 months, respectively).In disease resistant to irinotecan-based therapies, the oxaliplatin (FOLFOX4) regimen had superior efficacy to 5-FU/FA alone in a pivotal phase III trial (n = 816). Response rates and median durations of progression-free survival were 9.6% vs 0.7% and 5.6 vs 2.6 months, respectively. An oxaliplatin-induced cumulative peripheral sensory neuropathy (evident when total dose reaches approximate, equals 800 mg/m(2)) is dose limiting. The most frequently occurring grade 3 or 4 toxicities in oxaliplatin/5-FU/FA-recipients were neutropenia (up to 48%) and neurological toxicities (up to 18%). Gastrointestinal effects (diarrhoea [ approximate, equals 12%], nausea, vomiting, or mucositis/stomatitis [up to 6%]) are manageable. Withdrawals from oxaliplatin treatment were due to neuropathy (up to 10%), diarrhoea and/or vomiting (1%) or cutaneous toxicity (1%). Conclusion: As first-line therapy for metastatic colorectal cancer, oxaliplatin with 5-FU/FA consistently improves response rates and progression-free survival compared with various regimens of 5-FU/FA alone. The significant survival advantage shown by oxaliplatin/5-FU/FA (FOLFOX4) compared with first-line therapy with irinotecan/5-FU/FA (IFL) is encouraging but may require further confirmation. Oxaliplatin/5-FU/FA produces a significantly higher response rate and longer progression-free survival than 5-FU/FA in patients failing irinotecan-based therapies, and as such is also a useful second-line treatment. Although cumulative neurotoxicity is dose limiting, oxaliplatin has a manageable tolerability profile. Oxaliplatin as first- or second-line therapy is a valuable addition to the limited, but expanding, armamentarium of cytotoxic agents useful in advanced metastatic colorectal cancer.     

Clinical advances with topoisomerase I inhibitors in gastrointestinal malignancies

Phase III studies have shown irinotecan prolongs survival significantly when compared with either best supportive care or best infusional 5-fluorouracil (5-FU)-based chemotherapy in patients with 5-FU-resistant colorectal cancer. Phase I/II studies are investigating the combination of irinotecan with 5-FU, with thymidylate synthase inhibitors, notably raltitrexed, and with the oral fluoropyrimidines. Preliminary results suggest irinotecan and raltitrexed can safely be combined in the clinic and that this combination is active. The combination of irinotecan with the oral fluoropyrimidines also has produced promising results. A phase I study of irinotecan plus 5-FU/folinic acid showed high activity in first-line metastatic disease and further trials using the doses of 80 mg/m2 irinotecan plus 2 g 5-FU weekly are recommended. The combination of irinotecan with the De Gramont 5-FU regimen is feasible and active in patients with 5-FU-resistant metastatic disease. Alternating exposure to irinotecan and 5-FU may be as active as either treatment alone, and has been associated with overall response rates (ORRs) greater than 30% and encouraging median survival. The combination of irinotecan with oxaliplatin is also feasible and levels of response rates are in the region of 50% (especially with a 2-weekly administration schedule). In patients with advanced gastric cancer (including those with pretreated disease) ORRs of around 50% have been reported following administration of either cisplatin plus irinotecan or cisplatin plus docetaxel.     

Weekly high-dose 5-fluorouracil as 24-h infusion and folinic acid (AIO) plus irinotecan as second- and third-line treatment in patients with colorectal cancer pre-treated with AIO plus oxaliplatin

Our objective was to evaluate the efficacy and safety of high-dose 5-fluorouracil (5-FU) as a 24-h infusion and folinic acid (FA) (AIO regimen) plus irinotecan (CPT-11) after pre-treatment with AIO plus oxaliplatin (L-OHP) in colorectal carcinoma (CRC). Twenty-six patients with non-resectable distant CRC metastases were analyzed for second- or third-line treatment with AIO plus CPT-11 after pre-treatment with AIO plus L-OHP. On an outpatient basis, the patients received a treatment regimen comprising weekly 80 mg/m2 CPT-11 in the form of a 1-h i.v. infusion and 500 mg/m2 FA as a 1- to 2-h i.v. infusion, followed by 2000 mg/m2 5-FU i.v. administered as a 24-h infusion once weekly. A single treatment cycle comprised six weekly infusions followed by 2 weeks of rest. A total of 26 patients received 344 chemotherapy applications with AIO plus CPT-11. The main symptom of toxicity was diarrhea (NCI-CTC toxicity grade 3+4) occurring in five patients (19%; 95% CI 7-39%). Nausea and vomiting presented in two patients (8%; 95% CI 1-25%). The response rate of 26 patients can be summarized as follows: partial remission: n=7 (27%; 95% CI 12-48%); stable disease: n=9 (35%; 95% CI 17-56%) and progressive disease: n=10 (38%; 95% CI 20-59%). The median progression-free survival (n=26) was 5.8 months (range 3-13), the median survival time counted from the treatment start with the AIO plus CPT-11 regimen was 10 months (range 2-24) and counted from the start of first-line treatment (n=26) was 23 months (range 10-66). We conclude that the AIO regimen plus CPT-11 is practicable in an outpatient setting and well tolerated by the patients. Tumor control was achieved in 62% of the patients. The median survival time was 10 months and the median survival time from the start of first-line treatment (n=26) was 23 months.     

Metastatic colorectal cancer: current systemic treatment options

The treatment of colorectal cancer has become increasingly complex over recent years. With the emergence of new chemotherapy drugs and targeted agents, there has been great improvement in the prognosis of patients with metastatic colorectal cancer. This review summarises the evidence supporting the use of combination chemotherapy with oxaliplatin and/or irinotecan with fluorouracil (5-FU) for the treatment of colorectal cancer and outlines the pivotal trials. Phase III trials have demonstrated the superiority of combination chemotherapy over single-agent 5-FU, but the optimal sequencing and combination of treatment is yet to be determined. Oral fluoropyrimidine derivatives have been shown to be equivalent to bolus 5-FU treatment and these offer another option for the treatment of colorectal cancer, but further studies are required to evaluate their use with irinotecan and oxaliplatin. The use of newer targeted therapies, such as bevacizumab and cetuximab, alone and in combination with chemotherapy are discussed, and the most recent data supporting their use is outlined. Bevacizumab-containing regimens have been shown to be superior to those without for the first-line treatment of colorectal cancer, and cetuximab has demonstrated activity in combination with chemotherapy in both the first- and second-line setting. Other targeted agents, such as vatalanib and panitumumab, are discussed and early clinical studies with these agents show promising results.     

奥沙利铂联合亚叶酸钙及氟尿嘧啶治疗晚期大肠癌的临床分析

目的观察奥沙利铂联合亚叶酸钙及氟尿嘧啶方案治疗晚期大肠癌的临床疗效及毒副反应。方法 64例晚期大肠癌患者给予化疗方案为:L-OHP 130 mg/m2静脉点滴2 h,d1;CF 200 mg/m2,静脉点滴2 h,d1;5-FU 400 mg/m2静脉推注,后2 400 mg/m2微泵持续静脉滴注48 h。每2周重复,4周为1个周期,完成2个周期后判定疗效,按WHO标准评价客观疗效和毒副反应。结果全组64例均可评价疗效,其中完全缓解8例,部分缓解24例,稳定18例,进展14例,总有效率CR+PR=50.0%。中位肿瘤进展时间为5.6个月,中位生存时间为9.5个月。毒副反应主要是骨髓抑制、胃肠道反应及外周神经毒性。结论奥沙利铂联合亚叶酸钙及氟尿嘧啶方案治疗晚期肠癌患者的近期疗效较好,毒副反应可以耐受,值得进一步研究应用。     

西妥昔单抗联合化疗治疗转移性结直肠癌的观察

目的 观察西妥昔单抗联合化疗方案治疗转移性结直肠癌的近期疗效及不良反应.方法 11例经病理组织学确诊的转移性结直肠癌患者,给予西妥昔单抗联合FOLFOX方案治疗,西妥昔单抗首次给予负荷剂量400 mg/m2,每周给予维持剂量为250 mg/m2.结果 全组11例患者中,完全缓解1例,部分缓解5例,稳定2例,进展3例,有效率54.5％ (6/11),疾病控制率为72.7％ (8/11),中位肿瘤进展时间为8.4个月.主要不良反应为痤疮样皮疹(9例)和腹泻(6例).5例合并肝转移患者中经治疗后1例转化为可切除病灶.患者耐受良好,无治疗相关死亡.结论 西妥昔单抗联合FOLFOX方案治疗转移性结直肠癌疗效较好,不良反应多可耐受.     

Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan for wild-type KRAS metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines

The aim of this study is to prospectively evaluate the efficacy of combination chemotherapy with every second week cetuximab and irinotecan in patients with pretreated metastatic colorectal cancer harboring wild-type KRAS. Patients with wild-type KRAS metastatic colorectal cancer that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included. Cetuximab was administered at 500 mg/m(2) biweekly with irinotecan. The primary endpoint was response rate. The pharmacokinetics of cetuximab was also evaluated in 5 patients. From May 2009 to February 2010, a total of 31 patients were enrolled from five institutions. One patient was not eligible. Among the 30 patients who were treated with biweekly cetuximab plus irinotecan, partial response was observed in 9 patients. The objective response rate was 30.0% (95% confidence interval [CI], 14.7%-49.4%) and the disease control rate (complete response, partial response, or stable disease) was 76.7% (95% CI, 57.7%-90.0%). The median progression-free survival was 5.3 months and median overall survival was 10.8 months. Grade 3 skin toxicity was observed in 3 patients (10.0%) and one treatment related death due to pneumonia was observed. Combination chemotherapy with biweekly cetuximab and irinotecan was effective for pretreated metastatic colorectal cancer with wild-type KRAS.     

周剂量CPT-11治疗FOLFOX治疗失败的转移性结直肠癌

目的观察和评价依立替康(CPT-11)联合5-FU/LV治疗FOLFOX治疗失败的转移性结直肠癌的疗效及不良反应。方法入组患者共34例为转移性结直肠癌,经草酸铂及5-FU/LV治疗失败后,予CPT-11 60mg/m2,LV100mg/m2,5-FU 500mg/m2,每周1次,连续3周,每4周重复。患者最多接受6个周期,每例至少2周期化疗后评价疗效。结果全组34病例均可评价。PR为5例,SD为17例,有效率14.7%(95%可信区间3.6%～34.4%),疾病控制率64.7%(95%可信区间46.8%～85.6%),平均TTP为3.5个月(范围1.5～7.5个月)。主要不良反应为白细胞减少,恶心呕吐,手足综合征及延迟性腹泻,其不良反应发生率分别为67.4%(23/34),61.8%(21/34),64.8%(22/34),38.2%(13/34),均无IV度不良反应。结论周剂量伊立替康联合5-FU/LV为草酸铂治疗失败的转移性结直肠癌挽救治疗方案,不良反应轻微,适合于曾经强烈化疗患者。