Capecitabine plus oxaliplatin (xelox) in the treatment of chemotherapy-naive patients with metastatic colorectal cancer

Background Capecitabine and oxaliplatin are both synergistically active against metastatic colorectal cancer (MCRC). We evaluated our experience at two centers with capecitabine and oxaliplatin combination (XELOX) in previously untreated patients with MCRC. Patients and methods We reviewed medical records of 85 previously untreated patients with MCRC who received first-line XELOX regimen. Oxaliplatin was given at a dose of 130 mg/m² on day 1 in combination with capecitabine 1500 mg/m²/day on days 1–14 every 3 weeks. Results Seventy six of 85 patients were evaluated for response and toxicity. Patients with a follow up of less than 6 months were excluded from the study. Objective response rate was 46% including 8 complete responses (10.5%) and 27 partial responses (35.5%). Additionally, 20 patients (26.3%) had disease stabilization at least 3 months after the treatment. The patients were followed for a median 12.5 months (range 2–32). Median time to disease progression (TTP) was 11 months (range 2–27 months). Median overall survival (OS) time has not yet been reached. One-year survival rate was 66%. Toxicity was modest with infrequent grade 3–4 adverse effects. Conclusion XELOX is an active regimen against MCRC in the first-line setting with favorable toxicity profile. Our results appear to be comparable, if not superior, to the results of other reports of first-line XELOX therapy in respect to objective response rates, survival data, and safety profile. Convenience with oral administration of every 3-week schedule makes XELOX regimen a compelling therapeutic option in the treatment of first-line MCRC.     

奥沙利铂为主方案治疗进展期结直肠癌的临床观察

目的：观察含奥沙利铂联合方案治疗进展期结直肠癌的临床疗效及毒副反应.方法：经病理检查确诊的36例进展期结直肠癌患者分为A、B两组,分别予FOLFOX4（奥沙利铂、氟尿嘧啶和亚叶酸钙）方案及XELOX（奥沙利铂和卡培他滨）方案化疗,按WHO标准评价客观疗效和毒副反应.结果：入组36例均可评价疗效.A组24例,无CR者,PR9例,近期客观有效率37.5%,中位疾病进展时间（TTP）为7.0个月;B组12例,CR1例,PR4例,近期客观有效率41.7%,中位TTP为7.1个月,两组近期有效率无统计学差异.结论：与标准的FOLFOX4方案比较,XELOX方案治疗进展期结直肠癌疗效确切,毒副反应轻,尤其对于一般情况欠佳的患者耐受性好.     

奥沙利铂联合氟尿嘧啶类药物二线治疗晚期胃癌的临床研究

目的观察奥沙利铂联合氟尿嘧啶类药物二线治疗晚期胃癌的近期疗效和安全性。方法采用FOLFOX4方案，即奥沙利铂(L-OHP)85mg／m^2静脉滴注2h，d1，四氢叶酸钙(CF)200mg/m^2静脉滴注2h，d1、d2，注射后立即静脉推注氟尿嘧啶(5-FU)400mg/m^2，d1、d2，5-FU 600mg／m^2持续静滴d1、d2；每二周重复，28天为一周期。或改良XELOX方案，即L-OHP 85mg／m^2静脉滴注2h，d1、d15，卡培他滨(Cap)1250mg／m^2分两次口服d1～d14，28天为一周期。二个周期化疗结束后进行疗效评价。结果入组观察43例，总有效率为30.2％。其中FOLFOX4组有效率为31.6％，中位TTP为6个月；改良XELOX方案组总有效率为29．2％，中位TTP为5个月。两组总有效率和TTP比较差异无显著性。毒副反应主要为外周神经感觉异常，症状可逆。结论奥沙利铂联合氟尿嘧啶类药物二线治疗晚期胃癌疗效较高，毒副反应可耐受。     

Commentary on a phase III trial of bevacizumab plus XELOX or FOLFOX4 for first-line treatment of metastatic colorectal cancer: the NO16966 trial

Replacing infusional 5-fluorouracil (5-FU) leucovorin (LV) with oral capecitabine would be more convenient to patients, because it would lead to reduced hospital chair time and infusion-related toxicities. Previous trials with oral capecitabine-based regimens (other than XELOX [capecitabine/oxaliplatin]) have failed to demonstrate the equivalent efficacy of capecitabine based regimens to various 5-FU/oxaliplatin regimens (nonstandard FOLFOX [5-FU/LV/oxaliplatin] combinations); of note, these trials did not use the XELOX and standard FOLFOX regimens. An international phase III trial (NO16966) was initiated to demonstrate the noninferiority of XELOX to FOLFOX4 for the first-line treatment of metastatic colorectal cancer. The protocol was later amended to compare bevacizumab and chemotherapy versus placebo and chemotherapy. The efficacy data showed that XELOX was as effective as FOLFOX4 (progression-free survival [PPS; intent-to-treat population]: hazard ratio [HR], 1.04; 97.5% confidence interval, 0.93-1.16). Also, bevacizumab/chemotherapy(pooled with XELOX or FOLFOX) significantly prolonged PPS (HR 0.83; p=0.0023) compared with placebo and chemotherapy (XELOX/FOLFOX). In subgroup analysis, the addition of bevacizumab to XELOX (9.3 months vs. 7.4 months. HR.0.77; P=0.0026) and FOLFOX4(9.4 months vs. 8.6 months; HR, 0.89; P = 0.1871) prolonged PFS compared with respective placebo arms; however, it did not show statistical significance with the FOLFOX4 regimen. The adverse events were manageable and comparable between treatment arms.     

Capecitabine plus oxaliplatin (XELOX) versus 5‐fluorouracil/leucovorin plus oxaliplatin (FOLFOX‐6) as first‐line treatment for metastatic colorectal cancer

A regimen consisting of 5‐fluorouracil/leucovorin plus oxaliplatin (FOLFOX‐6) is widely used in France in the first‐line treatment of metastatic colorectal cancer (MCRC). The aim of our study was to demonstrate the non‐inferiority of capecitabine plus oxaliplatin (XELOX) versus FOLFOX‐6 for this indication. Patients were randomly assigned to receive XELOX or FOLFOX‐6 for 6 months. The primary endpoint was overall response rate (ORR) in the per‐protocol (PP) population; however, progression‐free and overall survival (OS), time to response and response duration were also assessed. A total of 306 patients were enrolled (XELOX n = 156; FOLFOX‐6 n = 150). ORR was 42 and 46% with XELOX and FOLFOX‐6, respectively, in the PP population. The difference between groups was 4.7%; the upper limit of the unilateral 95% confidence interval (14.4%) was below the non‐inferiority margin of 15%. In the intent‐to‐treat population, median progression‐free survival was 8.8 months with XELOX and 9.3 months with FOLFOX‐6, and median OS was 19.9 and 20.5 months, respectively. XELOX patients had significantly more grade 3/4 thrombocytopenia (12% vs. 5%) and diarrhoea (14% vs. 7%), but significantly less grade 3/4 neutropenia (5% vs. 47%), febrile neutropenia (0% vs. 6%) and neuropathy (11% vs. 26%) than FOLFOX‐6 patients. We conclude that XELOX is non‐inferior in terms of efficacy to FOLFOX‐6 in the first‐line treatment of MCRC, but has a different toxicity profile.     

Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials

This study evaluates the efficacy of capecitabine using data from a large, well-characterised population of patients with metastatic colorectal cancer (mCRC) treated in two identically designed phase III studies. A total of 1207 patients with previously untreated mCRC were randomised to either oral capecitabine (1250 mg m(-2) twice daily, days 1-14 every 21 days; n=603) or intravenous (i.v.) bolus 5-fluorouracil/leucovorin (5-FU/LV; Mayo Clinic regimen; n=604). Capecitabine demonstrated a statistically significant superior response rate compared with 5-FU/LV (26 vs 17%; P<0.0002). Subgroup analysis demonstrated that capecitabine consistently resulted in superior response rates (P<0.05), even in patient subgroups with poor prognostic indicators. The median time to response and duration of response were similar and time to progression (TTP) was equivalent in the two arms (hazard ratio (HR) 0.997, 95% confidence interval (CI) 0.885-1.123, P=0.95; median 4.6 vs 4.7 months with capecitabine and 5-FU/LV, respectively). Multivariate Cox regression analysis identified younger age, liver metastases, multiple metastases and poor Karnofsky Performance Status as independent prognostic indicators for poor TTP. Overall survival was equivalent in the two arms (HR 0.95, 95% CI 0.84-1.06, P=0.48; median 12.9 vs 12.8 months, respectively). Capecitabine results in superior response rate, equivalent TTP and overall survival, an improved safety profile and improved convenience compared with i.v. 5-FU/LV as first-line treatment for MCRC. For patients in whom fluoropyrimidine monotherapy is indicated, capecitabine should be strongly considered. Following encouraging results from phase I and II trials, randomised trials are evaluating capecitabine in combination with irinotecan, oxaliplatin and radiotherapy. Capecitabine is a suitable replacement for i.v. 5-FU as the backbone of colorectal cancer therapy.     

XELOX方案治疗晚期结直肠癌临床观察

目的比较卡培他滨(希罗达)联合奥沙利铂(XELOX)方案与亚叶酸钙、氟尿嘧啶(5-Fu)联合奥沙利铂(FOLFOX4)方案一线治疗晚期转移性结直肠癌的疗效和不良反应。方法将56例晚期结直肠癌患者随机分为两组,XELOX方案组(28例):卡培他滨(capecitabine,Xeloda)1000mg/m2,Bid,口服,d1~14;奥沙利铂(oxaliplatin)130mg/m2,静脉滴注,持续2h,d1;21 d为1周期。FOLFOX4方案组(28例):奥沙利铂85 mg/m2,静脉点滴2 h,d1;醛氢叶酸200 mg/m2,静脉点滴2 h,d1、2;氟尿嘧啶400 mg/m2,莫非氏管静脉推注d1、2;氟尿嘧啶600 mg/m2,静脉持续滴注(化疗泵),持续22 h,d1、2,14 d为1周期。结果 XELOX组总有效率(RR)50.0%,中位肿瘤进展时间(TTP)7.0个月;FOLFOX4组RR为46.4%,TTP为6.8个月;两组比较各项指标差异无显著性(P>0.05)。不良反应中XELOX组手足综合征发生率高于FOLFOX4组,Ⅲ、Ⅳ度中性粒细胞减少发生率低于FOLFOX4组。结论 XELOX方案一线治疗晚期结直肠癌有确切疗效,不良反应可耐受,与FOL-FOX4方案相当,但XELOX方案用药更为方便,安全性更好。     

XELOX (capecitabine plus oxaliplatin) as first-line treatment for elderly patients over 70 years of age with advanced colorectal cancer

The purpose of this phase II trial was to determine the efficacy and safety of the XELOX (capecitabine/oxaliplatin) regimen as first-line therapy in the elderly patients with metastatic colorectal cancer (MCRC). A total of 50 patients with MCRC aged > or = 70 years received oxaliplatin 130 mg m(-2) on day 1 followed by oral capecitabine 1000 mg m(-2) twice daily on days 1-14 every 3 weeks. Patients with creatinine clearance 30-50 ml min(-1) received a reduced dose of capecitabine (750 mg m(-2) twice daily). By intent-to-treat analysis, the overall response rate was 36% (95% CI, 28-49%), with three (6%) complete and 15 (30%) partial responses. In total, 18 patients (36%) had stable disease and 14 (28%) progressed. The median times to disease progression and overall survival were 5.8 months (95% CI, 3.9-7.8 months) and 13.2 months (95% CI, 7.6-16.9 months), respectively. Capecitabine was well tolerated: grade 3/4 adverse events were observed in 14 (28%) patients: 11 (22%) diarrhoea, eight (16%) asthenia, seven (14%) nausea/vomiting, three (6%) neutropenia, three (6%) thrombocytopenia, and two (4%) hand-foot syndrome. There was one treatment-related death from diarrhoea and sepsis. In conclusion, XELOX is well tolerated in elderly patients, with respectable efficacy and a meaningful clinical benefit response. Given its ease of administration compared with combinations of oxaliplatin with 5-FU/LV, it represents a good therapeutic option in the elderly.     

Chemotherapy permits resection of metastatic colorectal cancer: experience from Intergroup N9741.

BACKGROUND: Fluorouracil (5-FU), oxaliplatin and irinotecan combinations improve time to tumor progression (TTP), objective response and overall survival (OS) in patients with metastatic colorectal cancer (MCRC). Here we identify and describe patients treated on Intergroup study N9741 who initially had inoperable MCRC, but who obtained sufficient chemotherapeutic benefit to allow removal of their metastatic disease. PATIENTS AND METHODS: Patient research records in study arms (A) irinotecan/5-FU/leucovorin (LV) (IFL, n = 264), (F) oxaliplatin/5-FU/LV (FOLFOX4, n = 267) and (G) oxaliplatin/irinotecan (IROX, n = 265) were reviewed. TTP and median OS were calculated. RESULTS: Twenty-four (3.3%) of 795 randomized patients underwent curative metastatic disease resection [hepatectomy, 16; radiofrequency-ablation (RFA), six; lung resection, two]. Twenty-two out of 24 (92%) resected patients received an oxaliplatin-based regimen (FOLFOX4, 11; IROX, 11). Seven patients (29.2%) remain disease-free; relapses occurred mainly in the resected organ. Median OS in resected patients is 42.4 months, and median TTP is 18.4 months. All six patients treated with RFA have recurred. Four out of five (80%) patients who received chemotherapy following resection are disease-free. CONCLUSIONS: Resection of metastatic disease after chemotherapy is possible in a small but important subset of patients with MCRC, particularly after receiving an oxaliplatin-based chemotherapy regimen, with encouraging OS and TTP observed in these highly selected patients.     

A Phase II Study of Oxaliplatin, 5-Fluorouracil,Leucovorin, and High-Dose Capecitabine in Patients With Metastatic Colorectal Cancer

PurposeCapecitabine has shown similar efficacy to 5-fluorouracil (5-FU); a regimen containing 2 weeks of capecitabine/oxaliplatin (CapOx) has demonstrated noninferiority to infusional 5-FU/oxaliplatin/leucovorin (FOLFOX) for the treatment of metastatic colorectal cancer (mCRC). This phase II study explores the efficacy and safety of a 2-day course of oxaliplatin/capecitabine (2DOC), with oxaliplatin given on day 1 and capecitabine given orally every 8 hours in high doses over 6 doses, mimicking FOLFOX6.Patients and MethodsThis phase II study was conducted by the University of Wisconsin Carbone Cancer Center. Eligible patients with mCRC received oxaliplatin 100 mg/m² intravenously (I.V.) over 2 hours followed by leucovorin 20 mg/m² I.V. bolus and 5-FU 400 mg/m² I.V. bolus on day 1 and day 15. Capecitabine was administered at 1500 mg/m² orally every 8 hours over 6 doses starting on day 1 and day 15.ResultsA total of 45 patients were enrolled; 44 were evaluated for response. Seventeen patients (39%) had objective responses. Median time to progression was 6.8 months, and median overall survival (OS) was 17.5 months. The most common side effects were grade 1/2 neuropathy, fatigue, and nausea. Severe hand-foot syndrome (HFS) was rare.ConclusionThe overall response rate with the 2DOC regimen is similar to published CapOx regimens, and time to progression and OS are similar. The incidence of HFS, diarrhea, and mucositis were lower compared with published results of 2-week schedules of capecitabine. The 2DOC regimen merits further study as a more convenient regimen than infusional 5-FU with less HFS when compared with a 2-week administration of capecitabine.     

Capecitabine plus oxaliplatin for the first-line treatment of elderly patients with metastatic colorectal carcinoma: final results of the Southern Italy Cooperative Oncology Group Trial 0108

BACKGROUND: In patients with metastatic colorectal carcinoma (MCC), capecitabine has demonstrated a superior response rate (RR), equivalent disease progression-free (PFS) and overall survival (OS), and an improved overall tolerability profile compared with bolus 5-fluorouracil/leucovorin (5-FU/LV). The FOLFOX4 regimen, combining oxaliplatin with LV and bolus plus infusional 5-FU (LV5FU2), has been shown to improve RR and PFS versus LV5FU2, and it was more effective and less toxic than irinotecan plus bolus 5-FU/LV. Capecitabine (an oral fluoropyrimidine) may be an effective, well tolerated, and more convenient alternative to 5-FU/LV in combination with oxaliplatin, especially in older patients. METHODS: Elderly (> or = 70 years) patients with MCC were treated with a 3-weekly regimen of oxaliplatin at an initial dose of 85 mg/m(2) intravenously on Day 1 plus capecitabine 1000 mg/m(2) orally twice daily from Days 2 to 15 (XELOX regimen). In the absence of Grade > or = 2 hematologic toxicity, oxaliplatin was increased to 100 mg/m(2) in the second cycle, and in the absence of Grade > or = 2 nonhematologic adverse events during Cycle 2, capecitabine was increased to 1250 mg/m(2) twice daily in the third and subsequent cycles. After the first 35 patients (first series), the treatment protocol was amended so that only an oxaliplatin increase to 110 mg/m(2) and 130 mg/m(2) during Cycles 2 and 3, respectively, was planned in the remaining 41 patients (second series). RESULTS: Seventy-six patients with a median age of 75 years (range, 70-82 years) entered the current study. In the first series, the oxaliplatin dose was increased in 18 (51%) patients, and the capecitabine dose was increased in 4 (11%) patients. In the second series, the oxaliplatin dose was increased to 110 mg/m(2) in 26 (63%) patients, and to 130 mg/m(2) in 19 (46%) patients. In all, 2 complete and 29 partial responses were observed, for an overall RR of 41% (95% confidence interval [CI], 30-53%). The median PFS was 8.5 months (95% CI, 6.7-10.3 months), and the median OS was 14.4 months (95% CI, 11.9-16.9 months). In a multivariate analysis, the presence of disease symptoms affected both PFS and OS, whereas OS also was independently affected by male gender and disease spread. Age had no independent effect on PFS or OS. Five percent of patients developed Grade > or = 3 hematologic toxicity during treatment, Grade 3 peripheral neuropathy occurred in 8% of patients, and severe hand-foot syndrome in 13% of patients. CONCLUSIONS: Fit elderly patients with MCC showed a good RR to XELOX with only mild toxicity observed in most patients. XELOX, should, therefore be considered as an important therapeutic option for elderly patients with MCC.     

XELOX与FOLFOX6方案一线治疗晚期结直肠癌的近期疗效及不良反应比较

目的：比较卡培他滨（希罗达）联合奥沙利铂（XELOX）方案与亚叶酸钙、5-氟尿嘧啶（5-FU）联合奥沙利铂（FOLFOX6）方案一线治疗晚期转移性结、直肠癌的疗效和不良反应。方法：将62例晚期结、直肠癌患者随机分为两组,XELOX方案组（n=31）：卡培他滨（capecitabine,Xeloda）1000mg／m^2,2次／d,口服,第1天至第14天;奥沙利铂（oxaliplatin）130mg／m^2,静脉滴注,持续3h,第1天;21天为1周期。FOLFOX6方案组（n=31）：亚叶酸钙（CF）200mg／m^2,静脉滴注,第1天,5-FU前;5-FU400mg／m^2,静脉推注,第1天,2400mg／m^2,静脉持续滴注46h;奥沙利铂100mg／m^2,静脉滴注,持续3h,第1天;14天为1周期。结果：XELOX组缓解率（RR）为48．4％,中位肿瘤进展时间（TTP）6．8个月;FOLFOX6组RR为51．6％,TTP为7．1个月;两组比较各项指标差异无统计学意义（P〉0．05）。不良反应中XELOX组手足综合征发生率高于FOLFOX组,Ⅲ、Ⅳ度中性粒细胞减少发生率低于FOLFOX6组。结论：XELOX方案一线治疗晚期结、直肠癌有确切疗效,不良反应能耐受,与FOLFOX6方案相当,但XELOX方案用药更为方便,安全性更好。     

XELOX方案与FOLFOX4方案治疗转移性结直肠癌的临床观察

目的：观察两种常用化疗方案卡培他滨联合奥沙利铂方案（XELOX）与5-氟尿嘧啶/亚叶酸钙联合奥沙利铂方案（FOLFOX4）治疗转移性结直肠癌的临床疗效及不良反应。方法：48例晚期结直肠癌患者随机分成两组,XELOX组与FOLFOX4组。XELOX组25例,予卡培他滨联合奥沙利铂方案化疗,卡培他滨1000mg／m^2,口服,2次／日,第1—14天;奥沙利铂130mg／m^2,静脉点滴,第1天;21天1周期。FOLFOX4组23例,予5-氟尿嘧啶,亚叶酸钙联合奥沙利铂方案化疗,奥沙利铂85mg／m^2,静脉点滴,第1天;亚叶酸钙200mg／m^2,静滴2小时后予5-氟尿嘧啶400mg／m^2,推注,后续600mg／m^2持续静滴22小时,第1、2天;每2周重复,4周为1周期。两组均治疗2周期以上。按WHO标准评价客观疗效和不良反应。结果：48例均可评价疗效,XELOX组有效率48．0％（CR2,PR10）,中位TTP 7．1个月,MST 13．8个月,FOLFOX4组有效率47．8％（CR2,PR9）,中位TTP 7．3个月,MST 14．0个月。两组近期有效率无明显统计学差异。不良反应比较,手足综合征以XELOX组显著（P〈0．05）,Ⅲ-Ⅳ级恶心呕吐发生率FOLFOX4组高（P〈0．05）,余不良反应除腹泻外发生率以FOLFOX4组稍高,但无统计学意义。结论：XELOX方案与FOLFOX4方案治疗晚期结直肠癌疗效确切,不良反应能耐受。两组近期疗效相似,不良反应XELOX组更低。     

XELOX与FOLFOX4方案治疗进展期胃癌的随机对照临床研究

目的：评价卡培他滨联合奥沙利铂方案（XELOX）与氟尿嘧啶／亚叶酸钙联合奥沙利铂方案（FOL-FOX4）治疗进展期胃癌的临床疗效及不良反应。方法：54例进展期胃癌患者随机分成两组,XELOX组28例,卡培他滨1000mg／m2,口服,2次／日,第1—14天;奥沙利铂135mg／m2,静脉点滴,第1天,21天为1个周期。FOLFOX4组26例,奥沙利铂85mg／m2,静脉点滴,第1天;亚叶酸钙200mg／m。,静滴2h后予氟尿嘧啶400mg/m2,推注,后续600mg／m。持续静滴2h,第1、2天,每2周重复,4周为1周期。两组均治疗4周期以上。结果：XELOX组有效率53．57％,中位TTP5．8个月,MsT10个月,FOLFOX4组有效率46．15％,中位TTP5 ．7个月,MST9．8个月。两组近期有效率差异无显著性。不良反应比较,手足综合征以XELOX组显著（P〈0．05）,Ⅲ／Ⅳ级恶心呕吐发生率以FOLFOX4组显著（P〈0．05）,其余不良反应除腹泻外发生率以FOLFOX4组稍高,但差异无显著性。结论：XELOX方案与FOLFOX4方案治疗进展期胃癌疗效确切,不良反应能耐受,两组近期疗效相似,不良反应以XELOX组更易耐受,尤其对一般情况欠佳及老年的患者耐受性好。     

XELOX与FOLFOX6方案一线治疗晚期结直肠癌的近期疗效及不良反应比较

目的:比较卡培他滨(希罗达)联合奥沙利铂(XELOX)方案与亚叶酸钙、5-氟尿嘧啶(5-FU)联合奥沙利铂(FOLFOX6)方案一线治疗晚期转移性结、直肠癌的疗效和不良反应.方法: 将62例晚期结、直肠癌患者随机分为两组,XELOX方案组(n=31):卡培他滨(capecitabine,Xeloda)1000mg/m2,2次/d,口服,第1天至第14天;奥沙利铂(oxaliplatin)130mg/m2,静脉滴注,持续3h,第1天;21天为1周期.FOLFOX6方案组(n=31):亚叶酸钙(CF)200mg/m2,静脉滴注,第1天,5-FU前;5-FU 400mg/m2,静脉推注,第1天,2400mg/m2,静脉持续滴注46h;奥沙利铂100mg/m2,静脉滴注,持续3h,第1天;14天为1周期. 结果: XELOX组缓解率(RR)为48.4%,中位肿瘤进展时间(TTP)6.8个月;FOLFOX6组RR为51.6%,TTP为7.1个月;两组比较各项指标差异无统计学意义(P＞0.05).不良反应中XELOX组手足综合征发生率高于FOLFOX组,Ⅲ、Ⅳ度中性粒细胞减少发生率低于FOLFOX6组.结论: XELOX 方案一线治疗晚期结、直肠癌有确切疗效,不良反应能耐受,与FOLFOX6方案相当,但XELOX方案用药更为方便,安全性更好.     

Oral capecitabine: bridging the Atlantic divide in colon cancer treatment

5-Fluorouracil (5-FU) plus leucovorin (LV) has been the mainstay of treatment for colorectal cancer (CRC), with infused schedules more widely adopted in Europe and bolus schedules preferred in North America. However, the effective, oral fluoropyrimidine capecitabine is increasingly replacing intravenous (IV) 5-FU/LV on both sides of the Atlantic. Capecitabine generates 5-FU preferentially in tumor and is a well-established, first-line treatment for metastatic CRC. In this setting, capecitabine achieves a superior response rate, at least equivalent time to disease progression (TTP) and overall survival, and favorable safety compared with bolus 5-FU/LV. The benefits of capecitabine have been transfered into the adjuvant setting. Recent data from a large, international, randomized trial (Xeloda Adjuvant Chemotherapy Trial [X-ACT]) confirm that capecitabine (Xeloda, Roche Laboratories, Nutley, NJ) achieves favorable safety versus 5-FU/LV (Mayo Clinic regimen) and is at least as effective as IV 5-FU/LV in the adjuvant treatment of patients with resected stage III colon cancer. Capecitabine is also an effective and well-tolerated combination partner for oxaliplatin (XELOX) and irinotecan (XELIRI), achieving high efficacy with a good safety profile. An extensive phase III clinical trial program is further establishing the potential of the simplified capecitabine combinations to improve outcomes and unify treatment practices in the metastatic and adjuvant settings. New combinations with novel agents such as capecitabine/oxaliplatin plus erlotinib or bevacizumab are currently under investigation. Capecitabine has also shown promising activity and good tolerability in combination with radiotherapy in rectal cancer.     

Biweekly XELOX (capecitabine and oxaliplatin) as first-line treatment in elderly patients with metastatic colorectal cancer

ObjectiveThe combination of oxaliplatin and oral capecitabine (XELOX) has shown to be an active regimen in metastatic colorectal cancer (MCRC). However, the experience with XELOX in elderly patients is limited. This study aimed to evaluate the efficacy and safety of XELOX as first-line treatment in elderly patients with MCRC.Patients and MethodsPatients aged ≥ 70 years with previously untreated MCRC received oxaliplatin 85 mg/m² on day 1, every 2 weeks plus capecitabine 1000 mg/m² (or capecitabine 750 mg/m² if creatinine clearance was 30–50 mL/min) twice daily on days 1–7, every 2 weeks. Treatment was continued until progression, intolerable toxicity, or for a maximum of 12 cycles.ResultsThirty-five patients were enrolled. Median age was 78 years (range, 70–83). Patients received a median of 11 cycles of treatment. The objective response rate (ORR) was 49% and the tumor control rate was 86%. Median time to progression and overall survival were 8.6 (95% CI: 5.5–11.7) and 15.5 (95% CI: 9.6–21.3) months, respectively. Toxicities were generally mild to moderate. Major grade 1–2 toxicities were asthenia (40%), nausea (43%), and diarrhea (40%). No grade 4 toxicity was detected and grade 3 toxicities were reported in 17% of patients. There was no treatment-related death.ConclusionOur findings show that the biweekly XELOX regimen represents an effective and tolerable first-line treatment option for elderly patients with MCRC.     

Capecitabine versus 5-fluorouracil in colorectal cancer: where are we now?

Fluorouracil (5-FU) remains the most widely used agent for colorectal cancer. Capecitabine is a rationally designed 5-FU pro-drug developed to mimic the continuous infusion of 5-FU while avoiding complications and inconvenience of intravenous administration. Capecitabine is absorbed intact from the gastrointestinal tract, converted enzymatically to active 5-FU, and released directly into the tumor. Capecitabine’s efficacy and safety are shown in multiple phase III trials across different disease stages and therapy lines. Three randomized phase III trials demonstrated the equivalence of capecitabine plus oxaliplatin (XELOX) versus 5-FU/leucovorin (LV)/oxaliplatin (FOLFOX). The safety of capecitabine compared with 5-FU depends on the regimen of 5-FU used. The adverse event rate with oxaliplatin in combination with infusional 5-FU is similar to that of capecitabine plus oxaliplatin but is associated with more neutropenia and venous thrombotic events; capecitabine plus oxaliplatin-based regimens tend to be associated with more grade 3 diarrhea and hand-foot skin reaction. Combination therapy with capecitabine and irinotecan (CapeIRI) versus 5-FU/LV and irinotecan (FOLFIRI) had more variable results; some former schedules resulted in excessive treatment-related toxicity. More recent data show that lower capecitabine and irinotecan doses, different schedules, and combination with targeted agents (e.g, bevacizumab) have resulted in more favorable outcomes.     

ＸＥＬＯＸ方案治疗进展期胃癌的临床观察

目的　探讨奥沙利铂联合卡培他滨（ＸＥＬＯＸ）方案一线治疗进展期胃癌的疗效和不良反应。方法　回顾性分析７１例经病理组织学检查证实的胃癌患者,给予ＸＥＬＯＸ方案化疗,具体为：奥沙利铂１３０ｍｇ／ｍ^２静滴,第１天;卡培他滨１０００ｍｇ／ｍ^２口服,２次／日,第１～１４天,２１天为１周期。记录治疗的有效率（ＲＲ）、疾病进展时间（ＴＴＰ）、总生存时间（ＯＳ）和不良反应。结果　７１例患者共完成３２０个周期化疗,ＲＲ为４３７％（９５％ＣＩ：３６.３％ ～６２.９％）,包括ＣＲ５例（７.０％）,ＰＲ２６例（３６.６％）,中位ＴＴＰ为７.５个月（９５％ＣＩ：６.４～８.５个月）,中位ＯＳ为１１个月（９５％ＣＩ：８.２～１３.８个月）。主要不良反应以１～２级为主,３级不良反应包括恶心呕吐４例、腹泻５例、外周感觉神经症状５例、手足综合征７例和中性粒细胞缺乏６例,无化疗相关性死亡。结论　ＸＥＬＯＸ方案一线治疗进展期胃癌疗效较好,毒副反应可以耐受,使用方便,值得临床进一步研究。     

A phase II study of capecitabine plus oxaliplatin (XELOX)

Background: Capecitabine and oxaliplatin are both effective and well-tolerated monotherapies for the treatment of advanced colorectal cancer (CRC). Oxaliplatin has also been shown to be very effective when combined with 5-FU/LV in the first-line setting. Aim of the Study: Assess the efficacy and safety of capecitabine plus oxaliplatin (XELOX) in patients with previously untreated advanced CRC. Methods: Fifty-three patients with measurable disease received capecitabine 1,000 mg/m² twice daily on d 1–14 and oxaliplatin 130 mg/m² on d 1, every 3 wk. Of these, 52 were evaluable for safety and 49 for antitumor response. Results: There was a low rate of grade 1/2 adverse events; grade 3/4 events included leukopenia (10%), neutropenia (6%), thrombocytopenia (2%), nausea/vomiting (4%), and diarrhea (4%). The overall response rate was 39% (95% CI, 25–54%) and median time to disease progression was 7.8 mo. Conclusions: XELOX is an active and well-tolerated first-line treatment for advanced CRC. Randomized phase III studies are ongoing to compare XELOX with FOLFOX in view of the comparable efficacy and safety but superior convenience of XELOX therapy.