Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study.

PURPOSE: To compare the response rate, efficacy parameters, and toxicity profile of oral capecitabine with bolus intravenous (IV) fluorouracil plus leucovorin (5-FU/LV) as first-line treatment in patients with metastatic colorectal cancer. PATIENTS AND METHODS: We prospectively randomized 605 patients to treatment with oral capecitabine for 14 days every 3 weeks or 5-FU/LV by rapid IV injection daily for 5 days in 4-week cycles. RESULTS: The overall objective tumor response rate among all randomized patients was significantly higher in the capecitabine group (24.8%) than in the 5-FU/LV group (15.5%; P =.005). In the capecitabine and 5-FU/LV groups, median times to disease progression were 4.3 and 4.7 months (log-rank P =.72), median times to treatment failure were 4.1 and 3.1 months (P =.19), and median overall survival times were 12.5 and 13.3 months (P =.974), respectively. Capecitabine, compared with bolus 5-FU/LV treatment, produced a significantly lower incidence (P <.0002) of diarrhea, stomatitis, nausea, and alopecia. Patients treated with capecitabine also displayed lower incidences of grade 3/4 stomatitis and grade 3/4 neutropenia (P <.0001) leading to significantly less neutropenic fever/sepsis. Grade 3 hand-foot syndrome (P <.00001) and grade 3/4 hyperbilirubinemia were the only toxicities more frequently associated with capecitabine than with 5-FU/LV treatment. CONCLUSION: Oral capecitabine was more active than 5-FU/LV in the induction of objective tumor responses. Time to disease progression and survival were at least equivalent for capecitabine compared with the 5-FU/LV arm. Capecitabine also demonstrated clinically meaningful benefits over bolus 5-FU/LV in terms of tolerability.     

Oral doxifluridine plus leucovorin in metastatic colorectal cancer: randomized phase II trial with intravenous 5-fluorouracil plus leucovorin

This phase II study was designed to evaluate the efficacy and toxicities of oral doxifluridine plus leucovorin as a randomized trial with those of intravenous 5-fluorouracil (5-FU) plus leucovorin in previously untreated metastatic colorectal cancer (CRC). Patients with metastatic CRC were randomized in either group A (oral doxifluridine 1,000 mg/m /d plus leucovorin 30 mg/d on days 1 to 7 and 15 to 21 of each cycle), or group B (intravenous 5-FU 400 mg/m /d plus leucovorin 20 mg/m /d on days 1-5 of each cycle), with the cycles repeated every 4 weeks. Between July 1998 and May 2000, 77 patients were enrolled (38 in group A and 39 in group B). Response rates were 23.7% (95% CI, 11-42%) in group A, and 15.4% (95% CI, 0-25%) in group B on an intent-to-treat analysis. The median response durations of the two groups were similar with 5.6 months in group A and 5.5 months in group B. Progression-free survival and overall survival were 5.4 months and 14.9 months in group A; 4.7 months and 19.5 months in group B. Toxicities in both groups were generally mild and reversible. This study shows that a combination of oral doxifluridine plus leucovorin can be active and safe as a first-line treatment for patients with metastatic CRC.     

Randomized, open-label, phase III study of a 28-day oral regimen of eniluracil plus fluorouracil versus intravenous fluorouracil plus leucovorin as first-line therapy in patients with metastatic/advanced colorectal cancer.

PURPOSE: To compare the efficacy and tolerability of eniluracil (EU)/fluorouracil (5-FU) with that of 5-FU/leucovorin (LV) as first-line therapy for patients with metastatic/advanced colorectal cancer. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study (FUMA3008) conducted in the United States and Canada compared the safety and efficacy of EU/5-FU (11.5 mg/m(2)/1.15 mg/m(2) twice daily for 28 days every 35 days) with that of intravenous 5-FU/LV (425 mg/m(2)/20 mg/m(2) once daily for 5 days every 28 days) in patients with previously untreated metastatic colorectal cancer. Overall survival (OS) was the primary end point. RESULTS: A total of 981 patients were randomized and 964 patients received treatment (485 EU/5FU, 479 5FU/LV). Survival for EU/5-FU was not statistically equivalent (but not statistically inferior) to that for 5-FU/LV (hazard ratio, 0.880; 95% confidence interval [CI], 0.75 to 1.03). Median duration of survival was 13.3 months in the EU/5-FU group and 14.5 months in the 5-FU/LV group. Median duration of progression-free survival for EU/5-FU was statistically inferior to that of the control group (20.0 weeks [95% CI, 19.1 to 20.9 weeks] v 22.7 weeks [95% CI, 18.3 to 24.6 weeks]; P =.01). Both treatments were well tolerated. Diarrhea was the most common nonhematologic toxicity in both groups; treatment-related grade 3 or 4 diarrhea occurred in 19% of patients treated with EU/5-FU and 16% of patients receiving 5-FU/LV (P =.354). Grade 3 or 4 granulocytopenia occurred in 5% of EU/5-FU patients and 47% of 5-FU/LV patients. CONCLUSION: Safety profiles of both treatments were acceptable. Although antitumor activity was observed, EU/5-FU did not meet the protocol-specified statistical criteria for equivalence to 5-FU/LV in terms of OS.     

Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer.

PURPOSE: This randomized phase III trial compared the efficacy and safety of capecitabine with or without bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. PATIENTS AND METHODS: Patients were randomly assigned to receive capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks, alone or in combination with bevacizumab (15 mg/kg) on day 1. The primary end point was progression-free survival (PFS), as determined by an independent review facility. RESULTS: From November 2000 to March 2002, 462 patients were enrolled. Treatment arms were balanced. No significant differences were found in the incidence of diarrhea, hand-foot syndrome, thromboembolic events, or serious bleeding episodes between treatment groups. Of other grade 3 or 4 adverse events, only hypertension requiring treatment (17.9% v 0.5%) was more frequent in patients receiving bevacizumab. Combination therapy significantly increased the response rates (19.8% v 9.1%; P = .001); however, this did not result in a longer PFS (4.86 v 4.17 months; hazard ratio = 0.98). Overall survival (15.1 v 14.5 months) and time to deterioration in quality of life as measured by the Functional Assessment Of Cancer Treatment--Breast were comparable in both treatment groups. CONCLUSION: Bevacizumab was well tolerated in this heavily pretreated patient population. Although the addition of bevacizumab to capecitabine produced a significant increase in response rates, this did not translate into improved PFS or overall survival.     

Multicenter phase III study of uracil/tegafur and oral leucovorin versus fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer.

PURPOSE: This phase III study was designed to demonstrate equivalence in survival of oral uracil/tegafur (UFT) and oral leucovorin (LV) to conventional intravenous (IV) fluorouracil (5-FU) and LV in previously untreated metastatic colorectal carcinoma. Safety was also compared. PATIENTS AND METHODS: Eight hundred sixteen patients were randomized to receive either UFT (300 mg/m(2)/d) and LV (75 or 90 mg/d) for 28 days every 35 days or IV bolus 5-FU (425 mg/m(2)/d) and LV (20 mg/m(2)/d) for 5 days every 28 days. RESULTS: UFT/LV produced survival comparable to the IV 5-FU/LV regimen. Median survival was 12.4 months (95% confidence interval [CI], 11.2 to 13.6 months) with UFT/LV and 13.4 months (95% CI, 11.6 to 15.4 months) with 5-FU/LV (P =.630). The hazard ratio for survival was 0.964 (95.6% CI, 0.826 to 1.125), supporting equivalent survival. The overall response rate did not differ between treatment arms (UFT/LV, 11.7%; 5-FU/LV, 14.5%; P =.232). Median time to progression favored 5-FU/LV (UFT/LV, 3.5 months; 5-FU/LV, 3.8 months; P =.011), but tumor assessment schedules differed between arms. UFT/LV significantly improved safety compared with 5-FU/LV. Diarrhea, nausea and vomiting, and stomatitis and mucositis were significantly less frequent with UFT/LV, as was myelosuppression. Patients treated with UFT/LV had fewer episodes of febrile neutropenia (P <.001) and documented infections (P <.05). Increased bilirubin, without other liver function abnormalities, was observed more often with UFT/LV (P <.001). Concomitant medications were more frequent with 5-FU/LV, including use of antibiotics, growth factors, and antiemetics. CONCLUSION: UFT/LV provided a safer, more convenient oral alternative to a standard bolus IV 5-FU/LV regimen for metastatic colorectal cancer while producing equivalent survival.     

Randomized multicenter phase II trial of bolus plus infusional fluorouracil/leucovorin compared with fluorouracil/leucovorin plus oxaliplatin as third-line treatment of patients with advanced colorectal cancer.

PURPOSE: The addition of oxaliplatin to fluorouracil (FU) and leucovorin (LV) improves the outcome of patients with colorectal cancer (CRC). This multicenter study evaluated FU/LV with or without oxaliplatin in patients with metastatic CRC after disease progression on sequential fluoropyrimidine and irinotecan. PATIENTS AND METHODS: Two hundred fourteen patients were randomly assigned to receive LV 200 mg/m2 intravenously (IV) and FU 400 mg/m2 IV bolus, followed by FU 600 mg/m2 IV over 22 hours on days 1 and 2, every 2 weeks (LV5FU2); or LV and FU as described, plus oxaliplatin 85 mg/m2 IV over 2 hours on day 1 of the schedule (FOLFOX4). The primary end point was overall response. RESULTS: Baseline characteristics were similar in the two treatment arms. Objective response (complete + partial) rates for LV5FU2 versus FOLFOX4 were 2% v 13% (P = .0027), respectively. Median time to disease progression was 2.4 v 4.8 months (P < .0001), and median survival was 11.4 v 9.9 months (P = .20) for LV5FU2 and FOLFOX4, respectively. Among the 72 patients who crossed over from LV5FU2 to FOLFOX4, 6% responded. Symptomatic improvement was significantly better for patients in the FOLFOX4 arm (32% v 18% for LV5FU2, P = .05). Grade 3/4 toxicities for LV5FU2 and FOLFOX4 were neutropenia (13% and 42%, respectively), diarrhea (6% and 16%, respectively), and overall neuropathy (0% and 6%, respectively). CONCLUSION: In patients with metastatic CRC, the FOLFOX4 regimen was superior to LV5FU2 with a higher response rate and time to disease progression. FOLFOX4 is an effective regimen even after disease progression on two previous chemotherapy regimens with fluoropyrimidines and irinotecan.     

First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin.

PURPOSE: To evaluate the safety profile of capecitabine using data from a large, well-characterized population of patients with metastatic colorectal cancer treated in two phase II studies. In these trials, capecitabine achieved significantly superior response rates, equivalent time to disease progression and equivalent survival compared with 5-fluorouracil (5-FU)/leucovorin. PATIENTS AND METHODS: Patients (n = 1207) were randomized to either oral capecitabine (1250 mg/m2 twice daily, on days 1-14 every 21 days) or intravenous (i.v.) bolus 5-FU/leucovorin (Mayo Clinic regimen). RESULTS: Capecitabine demonstrated a safety profile superior to that of 5-FU/leucovorin, with a significantly lower incidence of diarrhea, stomatitis, nausea, alopecia and grade 3 or 4 neutropenia leading to significantly fewer neutropenic fever/sepsis cases and fewer hospitalizations. All patients in the capecitabine group received a starting dose of 1250 mg/m2 twice daily and the majority (66%) did not require dose modification for adverse events. In the 5-FU/leucovorin group, 58% of patients did not require dose reduction for toxicities. The capecitabine dose-modification scheme reduced the recurrence of key toxicities without compromising efficacy. In both treatment arms, patients with moderate renal impairment at baseline (estimated creatinine clearance 30-50 ml/min) experienced a higher incidence of grade 3 or 4 toxicities. This increase was more pronounced with 5-FU/leucovorin. CONCLUSIONS: Capecitabine is at least as effective, better tolerated and more convenient than i.v. 5-FU/leucovorin as treatment for patients with metastatic colorectal cancer. Analysis of data from two large phase III trials demonstrates that efficacy is not compromised in patients requiring a dose reduction for adverse events. The phase III data and an additional pharmacokinetic study support a lower starting dose in patients with moderate renal impairment at baseline (calculated creatinine clearance 30-50 ml/min) and a contra-indication in patients with severely impaired creatinine clearance at baseline (<30 ml/min). For patients with normal or mildly impaired renal function at baseline, the standard starting dose is well tolerated. The incidence and severity of adverse events in patients with moderate renal impairment at baseline who were treated with 5-FU/leucovorin was more pronounced, indicating that capecitabine provides a better-tolerated alternative.     

奥沙利铂联合羟基喜树碱与氟尿嘧啶治疗转移性结直肠癌的随机对照临床研究

背景与目的:化疗可提高转移性结直肠癌患者的生活质量,延长生存期.含氟尿嘧啶的联合方案是转移性结直肠癌的标准治疗方案,而其不良反应是化疗的限制性因素,影响患者的生活质量.因此探索新的方案显得十分必要.本研究观察及比较两种常用化疗方案[羟基喜树碱(HCPT)联合奥沙利铂(OXA)方案(HCPTOX)与氟尿嘧啶(5-FU)/亚叶酸钙(LV)联合OXA方案(FOLFOX4)]治疗转移性结直肠癌的临床疗效及不良反应.方法:47例转移性结直肠癌患者随机分成两组,HCPTOX组与FOLFOX4组.HCPTOX组24例,给予HCPT 6 mg/m2,静脉滴注,第1～5天; OXA 130 mg/m2,静脉滴注,第1天;21 d为1个周期.FOLFOX4组23例,给予0XA 85 mg/m2,静脉滴注,第1天;LV 200 mg/m2,静脉滴注2 h滴完后再给予5-FU 400 mg/m2,静脉推注,后续600 mg/m2持续静脉滴注22 h,第1、2天;每2周重复,4周为1个周期.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:入组47例均可评价疗效,HCPTOX组有效率为50.0%,中位TTP 7.8个月,MST 13.1个月,FOLFOX4组有效率47.8%,中位TTP 7.9个月,MST 13.3个月.两组近期有效率差异无显著性(P>0.05).不良反应比较,患者Ⅲ/Ⅳ级恶心、呕吐发生率以FOLFOX4组显著(P<0.05).除腹泻外,其他不良反应发生率以FOLFOX4组稍高,但差异均无显著性(P>0.05).结论:HCPTOX方案与FOLFOX4方案治疗转移性结直肠癌均疗效确切,不良反应均能耐受.两组近期疗效相似,不良反应以HCPTOX组较易耐受,尤其对一般情况欠佳及老年患者耐受性较好.     

Triplet combination with irinotecan plus oxaliplatin plus continuous-infusion fluorouracil and leucovorin as first-line treatment in metastatic colorectal cancer: a multicenter phase II trial.

PURPOSE: To evaluate the efficacy and tolerance of irinotecan (CPT-11) in combination with oxaliplatin (L-OHP) plus fluorouracil (5-FU)/leucovorin (LV) (de Gramont regimen) as first-line treatment of metastatic colorectal cancer (MCC). PATIENTS AND METHODS: Thirty-one patients with MCC who had not received prior therapy for metastatic disease were enrolled. Their median age was 60 years; performance status (World Health Organization) was 0 in 12, 1 in 14, and 2 in five patients; 19 patients (61%) had prior surgery, and 14 (45%) had adjuvant chemotherapy. CPT-11 was administered on day 1 at 150 mg/m(2) as a 90-minute intravenous (IV) infusion; L-OHP was administered on day 2 at 65 mg/m(2) as a 2-hour IV infusion; and on days 2 and 3, LV 200 mg/m(2) preceded 5-FU administration of 400 mg/m(2)/d initial IV bolus dose followed by 600 mg/m(2)/d 22-hour IV continuous infusion. The regimen was repeated every 2 weeks. RESULTS: All patients were assessable for toxicity and 30 for response to treatment. Complete response was achieved in two patients (6.5%) and partial response in 16 (51.6%) (overall response rate, 58.1%; 95% confidence interval, 40.7% to 75.4%); eight patients (25.8%) had stable disease, and five (16.1%) had disease progression. The median duration of response was 9 months, and the median time to disease progression was 13 months. Neutropenia grade 3 to 4 occurred in 14 patients (45%) and febrile neutropenia in two (6%). Diarrhea grade 3 to 4 was observed in 10 patients (32%), neurotoxicity grade 3 to 4 in three (9%), and asthenia grade 3 in two (10%). No treatment-related death has occurred. CONCLUSION: The triplet combination of 5-FU/LV + CPT-11 + L-OHP is a highly active regimen with manageable toxicity as front-line treatment in MCC.     

非小细胞肺癌抗血管生成药物治疗进展

经历了20余年的发展,抗血管生成治疗已经成为恶性肿瘤的重要治疗手段之一,其与化疗、放疗、表皮生长因子受体（epidermal growth factor receptor,EGFR）酪氨酸激酶抑制剂以及免疫药物联合均取得了公认的疗效。但肿瘤微环境治疗药物的特性也使其面临着特有的“瓶颈”：如何有效克服其耐药、早期评估疗效、筛选治疗优势人群、将毒性降至最小等。只有阐明这些问题,才能充分发挥其优势,将抗血管生成治疗提升至更高水平。     

Activity and toxicity of oxaliplatin and bolus fluorouracil plus leucovorin in pretreated colorectal cancer patients: a phase II study

The aim of the current study was to evaluate the activity and toxicity of a combination of oxaliplatin with bolus fluorouracil and leucovorin in colorectal cancer (CRC) patients pretreated for advanced disease with various schedules including continuous fluorouracil infusion. Thirty consecutive patients with pretreated advanced CRC received oxaliplatin 130 mg/m2 by 2-h infusion dl, leucovorin 100 mg/m2 by 1-h infusion followed by fluorouracil 425 mg/m2 i.v. bolus from day 1 to 3 every 3 weeks for a maximum of 6 cycles. The best overall response rate in an intent-to-treat analysis was 13% (2 complete responses and 2 partial responses) (95% CI, 1.2-25.5%) and 37% of patients obtained stable disease with a tumor growth control rate of 50% (95% CI, 32.1-67.9%). The median progression-free survival was 4.0 months (95% CI, 1.4-6.5 months) and median overall survival was 12.0 months (95% CI, 9.9-14.1 months). The independent prognostic factors for improved overall survival were a good performance status and a response/stabilization of disease to chemotherapy. Severe neutropenia was quite common (43.3% of patients and 14.4% of cycles), although complicated by fever only in one case (3.3% of patients). There was one toxic death. In conclusion, the study combination showed an interesting rate of tumor growth control in a cohort of patients previously treated for advanced disease with various schedules including continuous fluorouracil infusion.     

卡培他滨与氟尿嘧啶/亚叶酸钙联合奥沙利铂治疗晚期胃癌的随机对照临床研究

背景与目的：目前对进展期及转移性胃癌还没有标准的化疗方案,而且缺乏有效率高、毒副反应小、安全的化疗方案.毒副反应是晚期胃癌化疗的限制性因素,影响患者的生活质量.本研究观察及比较两种常用化疗方案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（FOLFOX4）治疗晚期胃癌的临床疗效及毒副反应,以期取得在较佳疗效保证的同时,毒副反应小,耐受性更好的效果.方法：48例晚期胃癌患者随机分成两组,XELOX组与FOLFOX4组.XELOX组25例,用卡培他滨联合奥沙利铂方案化疗,卡培他滨1000 mg/m^2,口服,2次/日,第1～14天;奥沙利铂130 mg/m^2,静脉点滴,第l天;2l d为1个周期.FOLFOX4组23例,用氟尿嘧啶/亚叶酸钙联合奥沙利铂方案化疗,奥沙利铂85 mg/m^2,静脉点滴,第1天;亚叶酸钙200 mg/m^2,静滴2 h后予氟尿嘧啶400 mg/m^2,推注,后续600 mg/m^2持续静滴22 h,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wH0标准评价客观疗效和毒副反应.结果：入组48例均可评价疗效,XELOX组有效率56.0%,中位TTP 5.8个月,MST 10个月,FOLFOX4组有效率47.8%,中位TTP 5.7个月,MST 9.8个月.两组近期有效率差异无显著性.毒副反应比较,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）,其余毒副反应除腹泻外发生率以FOIFOX4组稍高,但差异无显著性.结论：XELOX方案与FOLFOX4方案治疗晚期胃癌疗效确切,毒副反应能耐受.两组近期疗效相似,毒副反应以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.     

Randomized study of continuous infusion fluorouracil versus fluorouracil plus cisplatin in patients with metastatic colorectal cancer

One hundred twenty-two chemotherapy-naive patients with histologically confirmed colorectal adenocarcinoma were entered into a randomized trial comparing infusional fluorouracil (FU) versus cisplatin (CDDP) and FU. In both groups, patients received continuous infusion FU 1,000 mg/m2/d for 5 consecutive days every 4 weeks. Patients randomized to CDDP/FU also received CDDP 20 mg/m2 intravenous (IV) bolus on days 1 to 5 of each cycle. Patients were comparable in terms of age, performance status, baseline laboratory values, dominant sites of measurable disease, and percent of liver involvement. The partial response rate was significantly greater in patients who received CDDP/FU versus FU alone (25% v 3%, P = .001). Patients who received CDDP/FU experienced significantly greater toxicity compared with FU alone: grades 3 and 4 hematologic toxicity occurred in 22% and 0% of patients, respectively (P = .0001); grades 2 to 4 nausea and vomiting occurred in 80% and 15% of patients, respectively (P = .0001). There were no significant differences in either the duration of response (median, 6 and 4.7 months for CDDP/FU and FU groups, respectively) or survival (median 10, and 12 months, respectively). Compared with infusional FU alone, CDDP/FU provided a significantly greater partial response rate with increased toxicity, but it did not improve overall survival in patients with advanced colorectal carcinoma. Therefore, the use of CDDP/FU as routine therapy for the treatment of colorectal carcinoma cannot be recommended.     

Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial.

PURPOSE: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, increases survival when combined with irinotecan-based chemotherapy in first-line treatment of metastatic colorectal cancer (CRC). This randomized, phase II trial compared bevacizumab plus fluorouracil and leucovorin (FU/LV) versus placebo plus FU/LV as first-line therapy in patients considered nonoptimal candidates for first-line irinotecan. PATIENTS AND METHODS: Patients had metastatic CRC and one of the following characteristics: age > or = 65 years, Eastern Cooperative Oncology Group performance status 1 or 2, serum albumin < or = 3.5 g/dL, or prior abdominal/pelvic radiotherapy. Patients were randomly assigned to FU/LV/placebo (n = 105) or FU/LV/bevacizumab (n = 104). The primary end point was overall survival. Secondary end points were progression-free survival, response rate, response duration, and quality of life. Safety was also assessed. RESULTS: Median survival was 16.6 months for the FU/LV/bevacizumab group and 12.9 months for the FU/LV/placebo group (hazard ratio, 0.79; P = .16). Median progression-free survival was 9.2 months (FU/LV/bevacizumab) and 5.5 months (FU/LV/placebo); hazard ratio was 0.50; P = .0002. Response rates were 26.0% (FU/LV/bevacizumab) and 15.2% (FU/LV/placebo) (P = .055); duration of response was 9.2 months (FU/LV/bevacizumab) and 6.8 months (FU/LV/placebo); hazard ratio was 0.42; P = .088. Grade 3 hypertension was more common with bevacizumab treatment (16% v 3%) but was controlled with oral medication and did not cause study drug discontinuation. CONCLUSION: Addition of bevacizumab to FU/LV as first-line therapy in CRC patients who were not considered optimal candidates for first-line irinotecan treatment provided clinically significant patient benefit, including statistically significant improvement in progression-free survival.     

Phase II study of S-1 plus leucovorin in patients with metastatic colorectal cancer

BackgroundS-1, a novel oral fluoropyrimidine, is well tolerated in patients with metastatic colorectal cancer (mCRC). The response rate of S-1 for colorectal cancer is high, ranging from 35% to 40%. This study aimed to evaluate the safety and efficacy of S-1 combined with oral leucovorin (LV) to enhance antitumor activity in chemotherapy-naive patients with mCRC.Patients and methodsS-1 was given orally twice daily for two consecutive weeks at a daily dose of 80–120 mg, followed by a 2-week rest period, within a 4-week cycle. LV was given orally twice a day at a daily dose of 50 mg, simultaneously with S-1.ResultsOf the 56 patients with previously untreated mCRC, 32 (57%) had partial responses. The median follow-up period was 27.2 months. The median time to progression was 6.7 months (95% confidence interval 5.4–7.9). The median survival time was 24.3 months. There was no treatment-related death or grade 4 toxicity. The most common grade 3 toxic effects were diarrhea (32%), anorexia (21%), stomatitis (20%), and neutropenia (14%).ConclusionS-1 combined with LV therapy demonstrated promising efficacy and acceptable safety in chemotherapy-naive patients with mCRC without the concurrent use of irinotecan, oxaliplatin, or molecular-targeted drugs.     

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/m2,口服,2次/日,第1-14天;奥沙利铂130mg/m2,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/m2,静脉点滴,第1天;亚叶酸钙200mg/m2,静滴2小时后予5-氟尿嘧啶400mg/m2,推注,后续600mg/m2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%(CR 2,PR 10),中位TTP 7.1个月,MST 13.8个月,FOLFOX4组有效率47.8%(CR 2,PR 9),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.