Single-agent irinotecan as second-line weekly chemotherapy in elderly patients with advanced colorectal cancer

AIMS AND BACKGROUND: Irinotecan is a standard option for relapsed/refractory advanced colorectal cancer. Although in a recently reported, randomized trial it was found that a regimen of irinotecan once every 3 weeks was associated with a lower incidence of severe diarrhea than with weekly treatment with similar efficacy, there is no evidence in the literature that suggests the optimal dosing strategy for the drug, along with treatment efficacy and safety, following 5-fluorouracil/oxaliplatin-based chemotherapy in elderly patients. A phase II study has reported significantly reduced toxicity when irinotecan was administered once a week for 2 weeks, followed by a week rest. PATIENTS AND METHODS: From January 2004 to April 2005, we analyzed, retrospectively, our data on single-agent irinotecan as a second-line chemotherapy in elderly patients (> or =70 years) with advanced colorectal cancer. Twenty-three patients were evaluated. CPT-11 (80 mg/m2) was given as a 60-min intravenous infusion in repeated 21-day courses comprising weekly treatment for 2 consecutive weeks followed by a 1-week rest. Tumor measurements were obtained after every third course of therapy. Toxicity was assessed weekly using the National Cancer Institute Common Toxicity Criteria, version 2. RESULTS: The median number of treatment courses received per patient was 4 (range, 1-8). All patients were assessable for toxicity and 21 for response. The most frequently observed severe toxicities were diarrhea (grade 3, 13%) and neutropenia (grade 3, 30.4%; grade 4, 8.6%). Only 1 case of neutropenic fever occurred. Other hematological and non-hematological toxicities were mild and manageable. Objective partial responses were observed in 3 patients (13%). An additional 10 patients (43%) had stable disease as their best response. To date, 12 patients have progressed with a median time-to-progression of 4.3 months and a median survival of 8.3 months. CONCLUSIONS: A weekly irinotecan administration can induce tumor control in elderly patients with advanced colorectal cancer that has progressed during or shortly after 5-fluorouracil/oxaliplatin-based chemotherapy. However, a careful monitoring of hematological toxicity and special instructions to prevent and manage diarrhea are mandatory in this setting of patients.     

Phase I study of bevacizumab combined with irinotecan and S-1 as second-line chemotherapy in patients with advanced colorectal cancer

Purpose

The combination of an oral fluoropyrimidine derivative, S-1, and irinotecan has been reported to be a promising regimen for advanced colorectal cancer. However, the safety and efficacy of bevacizumab (BV) to combine with irinotecan and S-1 has not been determined. The aim of the study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of BV combined with irinotecan plus S-1, and to observe the safety and efficacy of this regimen as second-line chemotherapy in patients with advanced colorectal cancer.

Methods

This study initially had been planned as a phase I/II study. Eighty mg/m² of irinotecan on days 1 and 8, 80 mg/m² of S-1 for 14 consecutive days, and two doses of BV (Level 1; 10 mg/kg, Level ?1; 7.5 mg/kg) were administered on day 1 every 3 weeks.

Results

Fourteen patients were enrolled in phase I of the study between January 2008 and September 2010. Dose-limiting toxicities were diarrhea, abdominal pain, and infection. The MTD and RD of BV were determined to be 10 mg/kg and 7.5 mg/kg, respectively. The main adverse events were leukopenia, anorexia, and diarrhea. There were no treatment-related deaths. An independent review committee was scheduled to evaluate safety in phase I, but this trial closed early due to toxicity.

Conclusions

This study identified the risk of gastrointestinal toxicity with the combination of irinotecan, S-1 and BV as second-line chemotherapy in patients with advanced colorectal cancer.     

雷替曲塞联合伊立替康2周方案对比FOLFIRI方案二线治疗晚期结直肠癌的疗效观察

目的 观察雷替曲塞联合伊立替康2周方案治疗转移性结直肠癌的有效性和安全性。方法 经病理组织学或细胞学确诊的50例晚期转移性结直肠癌患者分为试验组（n=25）和对照组（n=25）。试验组方案： 雷替曲塞 2.5mg／m² 静滴,d₁;伊立替康（CPT-11） 180mg／m² 静滴,d₁。对照组方案：CPT-11 180mg／m² 静滴90min,d₁;亚叶酸钙 400mg／m² 静滴,d₁;5-FU 400mg／m² 静滴,d₁;5-FU 2400mg／m² 持续静滴46～48 h,d₁、d₂。两方案均2周为1周期,每周期评价毒副反应,每3个周期评价疗效,直至疾病进展或毒性不能耐受,最多治疗12个周期。结果 试验组获CR 1例,PR 4例,SD 18例,PD 2例;对照组获PR 2例,SD 19例,PD 4例。两组有效率（RR）分别为20％和8％,疾病控制率（DCR）分别为92％和84％,差异均无统计学意义（P＞0.05）。试验组1、2级转氨酶升高的发生率为24％,高于对照组的4％（P＜0.05）;对照组1、2级中性粒细胞减少、口腔黏膜炎的发生率均高于试验组（48％ vs. 20％,32％ vs. 8％,P＜0.05）。结论 雷替曲塞联合伊立替康2周方案与FOLFIRI方案的近期疗效相当,但毒副反应更轻,可以作为转移性结直肠癌的有效姑息治疗方案。     

Combining bevacizumab and panitumumab with irinotecan, 5-fluorouracil,and leucovorin (FOLFIRI) as second-line treatment in patients with metastatic colorectal cancer

Bevacizumab and panitumumab are human monoclonal antibodies with different targeting antigens, vascular endothelial growth factor, and epidermal growth factor receptor. This study examined the efficacy and safety of combining bevacizumab and panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) as the second-line therapy for patients with metastatic colorectal cancer (mCRC). Patients with mCRC, and previously failed with oxaliplatin-based chemotherapy, were given bevacizumab (3 mg/kg) and panitumumab (3 mg/kg) plus FOLFIRI every other week. From September 2008 to July 2012, 173 patients were included in the study. The response rate was 42.3 %, and the disease-controlled rate was 65.7 %. The median progression-free survival was 6.5 months, and the median overall survival was 15.4 months. Various adverse events (AE) including those known toxicities associated with antibody therapy were recorded. The overall AE rate was 64.5 % for grade 3–4. The treatment of combining bevacizumab and panitumumab plus FOLFIRI is effective and safe as a second-line therapy for patients with mCRC.     

FOLFIRI方案二线治疗晚期十二指肠癌的临床观察

目的 探讨FOLFIRI方案二线治疗晚期十二指肠癌的疗效和安全性。方法 回顾分析本院2008年6月至2016年1月接受FOLFIRI方案二线治疗的晚期十二指肠癌患者9例,分别采用RECIST 1.1版与NCI-CTC 4.0版标准评价近期疗效和不良反应。采用Kaplan-Meier法进行生存分析。结果 9例患者均可评价疗效和不良反应,共完成化疗41个周期,中位化疗4个周期（3～8个周期）。9例患者获PR 1例,SD 5例和PD 3例,总有效率和疾病控制率分别为11.1％和66.7％,中位无进展生存期为6.5个月,中位生存期为19.3个月。常见不良反应多为1～2级,主要为白细胞减少、中性粒细胞减少、贫血、乏力、恶心等。结论 FOLFIRI方案对一线治疗失败后的晚期十二指肠癌具有较好的疗效,且耐受性较好。     

Bi-weekly irinotecan hydrochloride and cisplatin as a second-line chemotherapy for patients with advanced gastric cancer

PURPOSE: To evaluate the effectiveness of bi-weekly administered irinotecan (CPT-11) and Cisplatin (CDDP) as a second-line chemotherapy for patients with advanced gastric cancer. METHODS: We included 22 patients who were resistant to 5-fluorouracil (5-FU) -based chemotherapy. CPT-11 (80 mg/m (2)) and CDDP (25 mg/m(2)) were administered bi-weekly on days 1 and 15 of a 4-week-cycle, on an outpatient basis except for the first time. Outcome variables include tumor response, toxicity, and survival. RESULTS: Among all patients, 8 responded to the therapy, yielding an overall response rate of 36.4% (complete response, n=1; partial response, n=7), while 14 did not respond (stable disease, n=9; progressive disease, n=5). The time to progression was 5.3 months, and the median survival was 10.6 months. Adverse reactions included Grade 3 or 4 leucopenia (n=4; 18.2%), Grade 3 or 4 thrombocytopenia (n=1; 4.5%) but all of these patients recovered soon (within one week). CONCLUSION: Bi-weekly CPT-11 and CDDP treatment was effective and should be considered as a second-line chemotherapy for patients with advanced gastric cancer who are resistant to 5-FU based chemotherapy.     

FOLFIRI方案治疗化疗后进展的晚期大肠癌的临床观察

目的探讨FOLFIRI方案治疗化疗后进展的晚期大肠癌的疗效和安全性。方法对32例化疗后进展的晚期大肠癌患者，予FOLFIRI方案化疗，伊立替康（CPT—11）180mg／m^2静滴第1天，亚叶酸钙（CF）200mg／m^2静滴第1～2天，5-氟尿嘧啶（5-FU）400mg／m^2静注第1～2天＋5-FU600mg／m^2持续静脉滴注22小时第1t2天，2周重复，连用3周期以上。按照WHO实体肿瘤近期客观疗效评定标准进行评价。结果全组32例均可评价疗效及毒副反应。完全缓解1例，部分缓解5例，稳定22例，进展4例，客观有效率为18．8％，平均疾病进展时间6．2个月，中位生存期9．0个月。毒副作用主要是食欲下降、恶心呕吐、延迟性腹泻及白细胞减少，多为Ⅰ／Ⅱ度。结论FOLFIRI治疗晚期大肠癌疗效较好，安全。     

FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study

BackgroundA targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy.Patients and methodsPatients were randomly assigned to receive FOLFIRI plus bevacizumab 5 or 10 mg/kg in 2-week cycles until disease progression. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), time to treatment failure (TTF), and safety.ResultsThree hundred and eighty-seven patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n = 181 and 10 mg/kg, n = 188). Safety was evaluated in 365 patients (5 mg/kg, n = 180 and 10 mg/kg, n = 185). The median PFS was 6.1 versus 6.4 months (hazard ratio, 0.95; 95% confidence interval [CI] 0.75–1.21; P = 0.676), and median TTF was 5.2 versus 5.2 months (hazard ratio, 1.01; 95% CI 0.81–1.25; P = 0.967), respectively, for the bevacizumab 5 and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups.ConclusionBevacizumab 10 mg/kg plus FOLFIRI as the second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment.Clinical trial identifierUMIN000002557.     

雷替曲塞单药二线治疗老年晚期结直肠癌的疗效分析

目的 观察单药雷替曲塞在老年晚期结直肠癌二线治疗中的疗效、安全性和影响预后的因素.方法 回顾性分析2012年1月至2016年12月在我院确诊并使用单药雷替曲塞二线化疗的老年晚期结直肠癌患者的资料.结果 符合入组条件患者27例,有效率为3.7％(1/27),疾病控制率为48.1％(13/27),中位无进展生存期为3.8个月,中位总生存期为10.0个月,毒副反应以Ⅰ～Ⅱ级为主,主要为粒细胞减少、贫血、转氨酶异常、疲乏及恶心呕吐.多因素分析显示PS评分状态及有无肝转移是影响患者预后的独立因素.结论 雷替曲塞单药二线治疗老年晚期结直肠癌安全有效,值得临床推广应用.     

Risk of arterial thromboembolic events in patients with advanced colorectal cancer receiving bevacizumab

BackgroundBevacizumab is an antiangiogenic mAb with efficacy against several cancers, but it is associated with risk of arterial thromboembolism (ATE). Further data are needed to determine the safety of bevacizumab.Patients and methodsWe recorded grade 3, 4, or 5 ATE events and other data (including age, baseline cardiovascular risk factors, history of ATE, and aspirin use) from 471 patients with metastatic colorectal cancer in the MAX (Mitomycin, Avastin, Xeloda) trial of capecitabine monotherapy versus capecitabine with bevacizumab with or without mitomycin C.ResultsBevacizumab-treated patients had 12 grade 3, 4, or 5 ATEs (3.8% incidence). ATEs occurred in 2.1% of patients >65 years, 5% of those with a history of ATE, and 5% of those with cardiac risk factors. Age, history of ATE, or vascular risk factors did not increase risk. Aspirin users had a higher incidence than nonusers (8.9% versus 2.7%) but had higher rates of vascular risk factors.ConclusionsBevacizumab was associated with a modestly higher risk of ATE, but safety was not significantly worse in older patients or patients with a history of ATE or vascular risk factors. The effect of aspirin in preventing ATE in patients receiving bevacizumab could not be determined from this study.     

Phase II clinical trial of second-line FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: AVASIRI trial

Objective

FOLFIRI is a standard chemotherapy regimen for the treatment of metastatic colorectal cancer. Although some studies have shown its efficacy in combination with bevacizumab as first-line chemotherapy, there are no data to support FOLFIRI plus bevacizumab as second-line chemotherapy in patients with this form of cancer. The aim of this study was to evaluate the efficacy and safety of FOLFIRI and bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer.

Methods

Eligible patients were ??20?years old, previously treated (except with irinotecan [CPT-11] and bevacizumab), with an Eastern Cooperative Oncology Group performance status of 0, 1, or 2, and adequate organ function. Twenty-five eligible patients received FOLFIRI with bevacizumab at a dose of 10?mg/kg given intravenously on day 1. All therapy was administered every 2?weeks until disease progression. The primary endpoint was the response rate.

Results

Twenty-five patients were enrolled between February 2008 and March 2009. The median age was 62 (range 38?C73) years, the male/female distribution was 20/5, 16 patients had performance status 0 and 9 had performance status 1, and the proportion of patients who were oxaliplatin pretreated/untreated was 16/9. The overall response rate was 32% (90% confidence interval [CI]: 17.0?C50.4%), with 8 patients showing partial responses, 15 with stable disease, and 2 with disease progression. Median progression-free survival was 11.6?months (95% CI: 6.9?C16.4). Median overall survival was 21.4?months (95% CI: 12.0?C30.8). The grade 3/4 adverse events with treatment were neutropenia (64%), leukopenia (16%), diarrhea (8%), anorexia (8%), and febrile neutropenia (8%). The bevacizumab-related grade 3/4 adverse event was hypertension, which was observed in 12% of patients.

Conclusions

The FOLFIRI plus bevacizumab regimen is an active, well-tolerated second-line chemotherapy treatment for patients with metastatic colorectal cancer.     

伊立替康联合雷替曲塞二线治疗晚期胃癌的疗效分析

目的 观察伊立替康（CPT-11）联合雷替曲塞二线治疗晚期胃癌的近期疗效和安全性。方法 对33例一线化疗方案治疗失败或缓解后再进展的晚期胃癌患者,应用CPT 11联合雷替曲塞进行化疗,具体为：CPT-11,200 mg／m2静滴 90 min,d1;雷替曲塞3 mg／m2 静滴15 min,d1;3周为1个周期。每2～3个周期按照RECIST 1.1版标准评价客观疗效,采用国立癌症研究所毒性判定标准（NCI CTC）4.0评价毒性反应,同时随访其生存情况。结果 33例均可评价近期疗效和毒副反应,无CR患者,PR 5例,SD 16例,PD 12例;有效率为15.2％,疾病控制率为63.6％,中位无进展生存期为3.3个月。常见毒副反应有贫血、恶心呕吐、白细胞减少、肝功能损害、迟发性腹泻、血小板减少及便秘,主要为1～2级。结论 CPT-11联合雷替曲塞二线治疗晚期胃癌有一定的疗效,毒副作用可耐受。     

CEA and CA19.9 as early predictors of progression in advanced/metastatic colorectal cancer patients receiving oxaliplatin-based chemotherapy and bevacizumab

We evaluated the changes of the tumor markers CEA and CA19.9 as early predictors of progression in metastatic colorectal cancer (mCRC) patients participating in a clinical study and receiving chemotherapy and bevacizumab (Bev). Seventy-two patients had high baseline CEA or CA19.9 serum levels. By ROC analyses, the areas under the curves were 0.83 for variable CEA cutoff values for distinguishing progressive disease (PD) versus stable disease (SD)/partial remission (PR)/complete remission (CR), and 0.80 for variable CA19.9 cutoff values for distinguishing PD versus SD/PR/CR. Rises in CEA and CA19.9 may early signal the occurrence of progression in mCRC patients receiving chemotherapy and Bev.     

贝伐珠单抗联合FOLFIRl方案一线治疗转移性结直肠癌的临床研究

目的评价贝伐珠单抗联合FOLFIRI方案一线治疗转移性结直肠癌的疗效和安全性。方法将42例转移性结直肠癌患者随机分为FOLFIRI组和FOLFIRI＋贝伐珠单抗组。FOLFIRI组（n=21）采用伊立替康（CPT一11,180mg／m2,d1）＋甲酰四氢叶酸钙（CF,400mg／m2,d1）＋氟尿嘧啶（5-FU,400mg／m2,静脉推注,d1;然后5-FU,2400mg／m2,以微量泵进行持续静脉滴注46小时）。FOLFIRI＋贝伐珠单抗组（n=21）采用贝伐珠单抗（每2周5mg／kg,d1）＋FOLFIRI方案。2周为1个周期,3个周期后评价疗效。两组患者均持续治疗至病情进展或毒性不能耐受。结果42例患者均可评价疗效和不良反应。FOLFIRI组和FOLFIRI＋贝伐珠单抗组的治疗有效率分别为28．6％和61．9％,FOLFIRI＋贝伐珠单抗组的有效率显著高于FOLFIRI组（P=0．03）。FOLFIRI＋贝伐珠单抗组的临床获益率明显高于FOLFIRI组（90．5％US61．9％,P：0．03）。FOLFIRI组和FOLFIRI＋贝伐珠单抗组中位无疾病进展时间（progression—freesurvival,PFS）分别为6．6个月和10．0个月（P=0．000）。两组的主要不良反应为迟发性腹泻和中性粒细胞减少,贝伐珠单抗组增加的不良反应主要有高血压（P=0．002）、出血（P=0．001）和蛋白尿（P=0．035）。结论FOLFIRI方案化疗联用贝伐珠单抗提高了晚期结直肠癌患者治疗的有效率和临床获益率,并延长了PFS,不良反应患者可以耐受。     

伊立替康联合顺铂对比伊立替康单药二线治疗晚期胃癌的临床研究

目的 探讨伊立替康（CPT-11）联合顺铂（DDP）方案与CPT-11单药治疗晚期胃癌的疗效、远期生存和毒副反应。方法 收集2012年6月至2014年1月复治晚期胃腺癌患者168例,随机分为CPT-11+DDP组（n=84）和CPT-11组（n=84）。CPT-11联合DDP方案：CPT-11 250 mg/m2静滴,d1;DDP 70 mg/m2静滴,d1,21天为1周期。CPT-11方案：CPT-11 250 mg/m2 d1静滴,21天为1周期。化疗2个周期后进行近期疗效评价,并比较两组的远期生存和不良反应。结果168例均可评价疗效。CPT-11+DDP组获CR 3例、PR 11例、SD 44例,有效率（RR）为167%,疾病控制率（DCR）为890%。CPT-11组获CR 1例、PR 12例、SD 41例,RR 为155%,DCR 为643%。两组RR和DCR的差异均无统计学意义（P=0834,P=0513）。CPT-11+DDP组和CPT-11组的无进展生存期分别为46个月和41个月（P=0522）,中位总生存期分别为138个月和125个月（P=0185）。亚组分析显示,在肠型腺癌中CPT-11+DDP组的中位总生存期优于CPT-11组（156个月vs. 136个月,P=0.016）。CPT-11+DDP组3～4级贫血、肝功能损害以及1～4级肾功能损害的发生率高于CPT-11组,而CPT-11组1～4级便秘和口腔黏膜炎的发生率均高于CPT-11+DDP组,差异均有统计学意义（P<0.05）。结论 CPT-11联合DDP方案较单药CPT-11方案二线治疗晚期胃癌并未带来生存获益,但对于晚期肠型胃癌具有优势,且安全性良好,值得进一步深入观察。     

FOLFIRI as second-line chemotherapy for advanced pancreatic cancer: a GISCAD multicenter phase II study

Purpose

The purpose of the present study was to evaluate the activity and the tolerability of the FOLFIRI regimen, administered as second-line chemotherapy in patients with locally advanced or metastatic pancreatic cancer after the failure of a gemcitabine-based regimen.

Methods

Patients with locally advanced/metastatic disease who received a first-line chemotherapy (one line only) with gemcitabine ± platinoid (cisplatin, oxaliplatin) and who had measurable disease conform with the RECIST criteria were eligible for the study. FOLFIRI consists of irinotecan 180 mg/m² iv on day 1, leucovorin (l-form) 200 mg/m² iv on day 1 and 2, 5-FU 400 mg/m² iv bolus on days 1 and 2, and 5-FU 600 mg/m² iv by ci for 22 h on days 1 and 2, repeated every 2 weeks. The primary end point was the response rate.

Results

Among the 50 enrolled patients, 4 partial responses (PR) (8 %) and 14 stable diseases were observed, for a disease control rate of 18/50 (36 %). Forty-one patients (82 %) have been pretreated with cisplatin/oxaliplatin+gemcitabine as first-line chemotherapy. The median progression-free and overall survivals were 3.2 and 5 months, respectively. The 6-month survival rate was 32 %. Grade 3–4 neutropenia and diarrhea occurred in 10 (20 %) and 6 (12 %) patients, respectively.

Conclusion

The FOLFIRI regimen showed a modest clinical activity in this quite heavily pretreated patients’ population with locally advanced or metastatic pancreatic cancer with a manageable toxicity profile.     

西妥昔单抗联合ＦＯＬＦＩＲＩ方案治疗晚期大肠癌的临床观察

目的：观察和评价西妥昔单抗（爱必妥）联合ＦＯＬＦＩＲＩ方案治疗国人晚期大肠癌患者的疗效及毒副反应。方法：回顾性分析２００６年６月～２００８年１２月我院经病理证实的晚期大肠癌患者４３例,爱必妥４００ｍｇ／ｍ２,第１次;以后２５０ｍｇ／ｍ^２,每周１次,或者５００ｍｇ／ｍ^２,每２周１次;伊立替康（开普拓）１８０ｍｇ／ｍ^２,第１天,静滴３０分钟;亚叶酸钙２００ｍｇ／ｍ^２,第１、２天,静滴２小时;氟尿嘧啶（５－ＦＵ）４００ｍｇ／ｍ^２,静推,第１、２天,５－ＦＵ６００ｍｇ／ｍ^２,持续静滴２２小时,第１、２天,每２周重复。每例至少接受４周期化疗后评价疗效。结果：全组４３例均可评价,有效率（ＣＲ＋ＰＲ）为３４．９％ （１５／４３）,ＳＤ４８．８％ （２１／４３）,ＰＤ１６．３％ （７／４３）。中位疾病进展时间（ＴＴＰ）８．９个月,中位生存期（ＯＳ）１９．３个月。治疗相关毒副反应主要为皮疹、迟发性腹泻及中性粒细胞减少。结论：西妥昔单抗联合ＦＯＬＦＩＲＩ方案治疗国人晚期大肠癌疗效肯定,可使大部分患者临床获益,其毒副反应可以耐受。     

Phase I trial of weekly irinotecan combined with UFT as second-line treatment for advanced colorectal cancer

The aim of this study was to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly Irinotecan (CPT-11) plus UFT, and to assess the antitumour activity of this combination as second-line chemotherapy in patients with advanced colorectal carcinoma, 31 patients with measurable advanced colorectal carcinoma were treated. Cohorts of 3 patients received increasing dose levels of the combination. Levels 1 to 4 included a fixed dose of oral (p.o.) UFT (250 mg/m²/day) for 21 days of a 28-day cycle combined with increasing intravenous (i.v.) doses of CPT-11 (80, 100, 110 and 120 mg/m²) on days 1, 8 and 15. Levels 5 and 6 included a higher fixed dose of oral UFT (300 mg/m²) combined with increasing i.v. doses of CPT-11 (100 and 110 mg/m²) on days 1, 8 and 15. 147 courses were administered. MTD were reached at level 4 (2 cases of grade 4 diarrhoea and 1 grade 3 asthenia), and level 6 (1 grade 4 diarrhoea, 1 grade 3 diarrhoea and 1 grade 3 febrile neutropenia). Responses in 30 evaluable patients were: 3 partial responses (10%), 15 stable disease (50%) and progressive disease in 12 patients (40%). Median time to progression was 4.5 months (95% Confidence Interval (CI): 3.4–6.6 months) and median survival was 11 months (95% CI: 7.9–14.1 months). The recommended doses for phase II trials are: (a) CPT-11 110 mg/m² i.v. on days 1, 8 and 15 every 28 days plus UFT 250 mg/m² p.o. on days 1 through to 21 or (b) CPT-11 100 mg/m² and UFT 300 mg/m².     

Phase II study of weekly irinotecan (CPT-11) as second-line treatment of patients with advanced colorectal cancer

This phase II trial studied the antitumor effect and toxicity of weekly irinotecan (CPT-11, 125 mg/m² 60 min iv infusion, weekly for 4 wk plus 2 wk rest) as second-line chemotherapy in patients with advanced colorectal cancer (CRC) resistant or refractory to prior 5-fluorouracil (5-FU) therapy. Sixty-nine patients with adenocarcinoma (57% in the colon and 43% in the rectum) were enrolled. The median number of treatment cycles received per patient was 4 (range, 1–6). Overall response rate was 18% (95% CI, 9–26), with 4 complete responses (6%) and 8 partial responses (12%), and a median duration of response of 8.1 mo (95% CI, 4.2–12.1). Stable disease was observed in 19 patients (28%). The median time to disease progression was 5.2 mo (95% CI, 4.3–6.1), and the median overall survival was 13.3 mo (95% CI, 9.8–16.8 months). The toxicity profile was favorable: grade 3/4 delayed diarrhea was observed in 10 patients (14.5%) in one cycle each, and grade 3/4 neutropenia in 6 patients (8.7%) and 6 cycles (3.3%). No febrile neutropenia or infection was documented. Grade 3/4 nausea and vomiting were reported in 1 (1.4%) and 7 patients (10.1%), respectively. In conclusion, this phase II trial showed a response rate and a toxicity profile of weekly CPT-11 in line with the results of prior phase II studies.