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.     

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.     

Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (mGemOx): final results of a multicenter randomized phase II trial in advanced pancreatic cancer.

BACKGROUND: To compare the efficacy and safety of three different chemotherapy doublets in the treatment of advanced pancreatic cancer (PC). PATIENTS AND METHODS: At total of 190 patients were randomly assigned to receive capecitabine 1000 mg/m(2) twice daily on days 1-14 plus oxaliplatin 130 mg/m(2) on day 1 (CapOx), capecitabine 825 mg/m(2) twice daily on days 1-14 plus gemcitabine 1000 mg/m(2) on days 1 and 8 (CapGem) or gemcitabine 1000 mg/m(2) on days 1 and 8 plus oxaliplatin 130 mg/m(2) on day 8 (mGemOx). Treatment cycles were repeated every three weeks. The primary end point was progression-free survival (PFS) rate at 3 months; secondary end points included objective response rate, carbohydrate antigen 19-9 response, clinical benefit response, overall survival and toxicity. RESULTS: The PFS rate after 3 months was 51% in the CapOx arm, 64% in the CapGem arm and 60% in the mGemOx arm. Median PFS was estimated with 4.2 months, 5.7 months and 3.9 months, respectively (P = 0.67). Corresponding median survival times were: 8.1 months (CapOx), 9.0 months (CapGem) and 6.9 months (mGemOx) (P = 0.56). Grade 3/4 hematological toxicities were more frequent in the two Gem-containing arms; grade 3/4 non-hematological toxicity rates did not exceed 15% in any arm. CONCLUSION: CapOx, CapGem and mGemOx have similar clinical efficacy in advanced PC. Each regimen has a distinct but manageable tolerability profile.     

Sex differences in the safety of S‐1 plus oxaliplatin and S‐1 plus cisplatin for patients with metastatic gastric cancer

Previous studies have shown sex‐related differences in the incidence of adverse events following treatment with fluoropyrimidines, however the mechanism of this difference is unknown. We examined sex‐related differences in the safety of S‐1 plus oxaliplatin (SOX) and S‐1 plus cisplatin (CS) in 663 metastatic gastric cancer patients taking part in a phase III study. The incidences of leukopenia (odds ratio [OR] 1.9; P = .015), neutropenia (OR 2.2; P = .002), nausea (OR 2.0; P = .009), and vomiting (OR 2.8; P < .001) were increased in women versus men treated with SOX, while vomiting (OR 2.9; P < .001) and stomatitis (OR 1.8; P = .043) were increased in women versus men treated with CS. In contrast, male patients treated with CS experienced thrombocytopenia more often (OR 0.51; P = .009). The mean relative dose intensity of S‐1 in SOX was 75.4% in women and 81.4% in men (P = .032). No difference in efficacy was observed between women and men undergoing either regimen. Sex‐related differences in adverse reactions during SOX and CS treatment were confirmed in this phase III study. Further translational research studies are warranted to pursue the cause of this difference.     

A randomized phase II study to compare oxaliplatin plus 5-fluorouracil and leucovorin (FOLFOX4) versus oxaliplatin plus raltitrexed (TOMOX) as first-line chemotherapy for advanced colorectal cancer

Introduction

The aim of this study was to compare TOMOX versus FOLFOX4 as first-line treatment of advanced colorectal cancer (CRC).

Materials and methods

191 chemotherapy-na?ve patients were randomized to receive TOMOX or FOLFOX4. Patients were evaluated every 3?months and chemotherapy was continued until disease progression or unacceptable toxicity. Overall response rate was the primary endpoint.

Results

183 patients were included in the intent-to-treat analysis (92 TOMOX and 91 FOLFOX4). Overall response rate was 45.6 and 36.3?% (p?=?0.003) for TOMOX and FOLFOX4, respectively. No statistically significant differences were observed in overall survival (15.6 and 17.2?months; p?=?0.475); progression-free survival (7.7 and 8.7?months; p?=?0.292), and response duration (6.4 and 7.6?months; p?=?0.372) for TOMOX and FOLFOX4, respectively. Grades 3 and 4 neutropenia (p?p?=?0.028) were more common with the FOLFOX4 regimen, while hepatic disorders and asthenia were higher in TOMOX group (p?=?ns). There were two treatment-related deaths in the FOLFOX4 arm and one in the TOMOX arm. Quality of life analysis based on the SF-36 revealed differences between the two regimens for physical and mental composite scores after 6?weeks, and for body pain and emotional role functioning after 6 and 12?weeks; all of these favored the FOLFOX4 arm (p????0.05).

Conclusions

TOMOX and FOLFOX4 seem to have similar efficacy and are well tolerated in the first-line treatment for advanced CRC with different profiles of toxicity. The convenient TOMOX regimen may offer an alternative to fluoropyrimidine-based regimens.     

Capecitabine plus oxaliplatin (xelox) versus protracted 5-fluorouracil venous infusion plus oxaliplatin (pvifox) as first-line treatment in advanced colorectal cancer: a GOAM phase II randomised study (FOCA trial)

This phase II randomised trial compares oxaliplatin plus protracted infusion of 5-fluorouracil (pviFOX) or oxaliplatin plus capecitabine (XELOX) in the first-line treatment of advanced colorectal cancer (ACRC). Methods: From December 2001 to March 2005, 118 patients were randomised to arm A ( pviFOX: pvi5-FU by a central venous catheter 250 mg/m2/daily d1-21 + oxaliplatin 130 mg/m2 d1 q3w) (56 pts) or arm B (XELOX: capecitabine 1000 mg/m2 po bid d1-14 + oxaliplatin at the same schedule) (62 pts). Results: Patient characteristics were well-balanced between the two arms. Median number of complete cycles was six. The objective responses were: CR 1 (1.7%) and 3 (4.8%), PR 26 (46.4 %) and 24 (38.7%), SD 13 (23.2%) and 20 (32.3%), P 13(23.2%) and 10 (16.1%), not evaluable 3 (5.4%) and 5 (8.1 %) in arms A and B, respectively; the CR + PR rate was 48.2% (95% confidence limits 34.6%–61.9%) versus 43.5 % (31.0%–56.7%). Median TTP was 7 versus 9 months, respectively. About 50% of the patients with symptoms or low performance status at baseline experienced improvement without major differences between the two arms. G3–4 diarrhoea was observed in 14.0% versus 8.2%, G3 stomatitis in 3.7% versus 0, and G3 neurotoxicity in 18.5% versus 24.6% in arms A and B, respectively. Eight patients in arm A (14.8%) had venous line problems that obliged the temporary suspension (six cases) or stopping (two cases) of the 5-FU infusion. Conclusion: Both pviFOX and XELOX are effective and safe first-line treatments for patients with ACRC. By avoiding intravenous (i.v.) administration by a central catheter, XELOX is favoured in clinical practice.     

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.     

Influence of mRNA expression of epiregulin and amphiregulin on outcome of patients with metastatic colorectal cancer treated with 5‐FU/LV plus irinotecan or irinotecan plus oxaliplatin as first‐line treatment (FIRE 1‐trial)

Our aim was to investigate the impact of EREG and AREG mRNA expression (by RT‐qPCR) in patients with metastatic colorectal cancer (mCRC). In addition, epidermal growth factor receptor (EGFR) expression (by immunohistochemistry) as well as RAS‐and PIK3CA‐mutations (by pyrosequencing) were assessed. Tumors of 208 mCRC patients receiving 5‐fluorouracil/leucovorin plus irinotecan (FUFIRI) or irinotecan plus oxaliplatin (mIROX) within the FIRE‐1 trial were analyzed for mutations. Molecular characteristics were correlated with response, progression‐free survival (PFS), overall survival (OS). mRNA expression was evaluated using ROC‐analysis in 192 tumors (AREG high n = 31 vs. low n = 161; EREG high n = 89 vs. low n = 103). High versus low AREG expression was associated with PFS of 10.0 versus 8.0 months (HR = 0.62, 95% CI: 0.402–0.940, p = 0.03) and OS of 24.6 versus 18.7 months (HR = 0.72, 95% CI: 0.476–1.078, p = 0.11). High versus low EREG expression correlated with prolonged PFS (9.4 vs. 6.8 months, HR = 0.62, 95% CI: 0.460–0.846, p = 0.002) and OS (25.8 vs. 15.5 months, HR = 0.48, 95% CI: 0.351–0.657, p < 0.001). The positive prognostic effect of high EREG expression was confirmed in a multivariate analysis and was neither affected by EGFR expression nor by mutations of RAS‐ and PIK3CA‐genes. EREG expression appears as an independent prognostic marker in patients with mCRC receiving first‐line irinotecan‐based chemotherapy.     

Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study

BackgroundTo demonstrate the noninferiority of capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid and oxaliplatin (FOLFOX-4) as second-line therapy in patients with metastatic colorectal cancer after prior irinotecan-based chemotherapy.Patients and methodsA total of 627 patients were randomly assigned to receive XELOX (n = 313) or FOLFOX-4 (n = 314) following disease progression/recurrence or intolerance to irinotecan-based chemotherapy. The primary end point was progression-free survival (PFS).ResultsPFS for XELOX was noninferior to FOLFOX-4 [hazard ratio (HR) = 0.97; 95% confidence interval (CI) 0.83–1.14] in the intention-to-treat (ITT) population. Median PFS was 4.7 months with XELOX versus 4.8 months with FOLFOX-4. The robustness of the primary analysis was supported by multivariate and subgroup analyses. Median overall survival in the ITT population was 11.9 months with XELOX versus 12.5 months with FOLFOX-4 (HR = 1.02; 95% CI 0.86–1.21). Treatment-related grade 3/4 adverse events occurred in 50% of XELOX- and 65% of FOLFOX-4-treated patients. Whereas grade 3/4 neutropenia (35% versus 5% with XELOX) and febrile neutropenia (4% versus < 1%) were more common with FOLFOX-4, grade 3/4 diarrhea (19% versus 5% with FOLFOX-4) and grade 3 hand–foot syndrome (4% versus < 1%) were more common with XELOX.ConclusionXELOX is noninferior to FOLFOX-4 when administered as second-line treatment in patients with metastatic colorectal cancer.     

希罗达联合奥沙利铂治疗晚期胃癌的临床疗效观察

目的：观察希罗达（Xeloda）联合奥沙利铂（L—OHP）治疗晚期胃癌的疗效和毒副作用。方法：L—OHP130mg／m2，加入5％GS500rrd中静脉滴注2小时，第一天，Xeloda1000mg／m2，2次／d口服，第1—14天，21天为一周期，连用2个周期后评价疗效。结果：23例患者中，CR1例PR11例SD8例PD3例，RR52．2％，中位疾病进展时间（TTP））5．8个月（3—8个月），中位生存期（MST）11个月（6—17个月），1年生存率34．8％。毒副反应主要为骨髓抑制、消化道反应、神经毒性和手足综合征，大多能耐受。结论：希罗达联合奥沙利铂治疗晚期胃癌具有较好的疗效，毒副作用小，能显著提高患者的生活质量，值得临床推广。     

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.     

卡培他滨联合奥沙利铂与替吉奥联合奥沙利铂治疗进展期胃癌的对比研究

目的　比较卡培他滨与替吉奥（Ｓ-１）分别联合奥沙利铂（Ｌ-ＯＨＰ）治疗进展期胃癌的有效性和安全性。方法 ９４例进展期胃癌患者分为两组,Ａ组（ＸＥＬＯＸ方案）５４例,具体为：Ｌ-ＯＨＰ１３０ｍｇ／ｍ２静滴２ｈ,ｄ１;卡培他滨１０００ｍｇ／ｍ２ｂｉｄ,ｄ１～ｄ１４,３周为１周期;Ｂ组（Ｌ-ＯＨＰ＋Ｓ-１）４０例,具体为：Ｌ-ＯＨＰ１３０ｍｇ／ｍ２静滴２ｈ,ｄ１;Ｓ-１４０ｍｇ／ｍ２分早晚２次餐后服用,ｄ１～ｄ１４,３周为１周期。２个周期评价疗效及毒性。治疗前后分别进行血常规、肝肾功能、胸腹部ＣＴ扫描及胃镜等检查,观察肿瘤病灶大小变化,记录临床症状变化和化疗毒副反应,随访两组的疾病进展时间和生存期。结果　９４例均可评价疗效,Ａ、Ｂ两组的有效率分别为４６.４％和５１.８％,疾病控制率为７２.８％和７９.４％,中位疾病进展时间为６.６个月和６.８个月,中位生存时间为１３.５个月和１４.０个月,上述两组差异均无统计学意义（Ｐ＞０.０５）。两组毒副反应主要包括血液学毒性、肝肾功能异常、恶心呕吐、腹泻、末梢神经毒性和手足综合征等,以１～２级为主,均可耐受。结论　卡培他滨联合Ｌ-ＯＨＰ与Ｓ-１联合Ｌ-ＯＨＰ治疗进展期胃癌的疗效相当,不良反应均可耐受。     

Alternating irinotecan with oxaliplatin combined with UFT plus leucovorin (SCOUT) in metastatic colorectal cancer

Tegafur-uracil (UFT) plus leucovorin (LV, folinic acid) with alternating irinotecan and oxaliplatin were effective and well tolerated in patients with metastatic colorectal cancer (mCRC) in a phase I study. This study expanded the maximum tolerated dose group. Patients aged >or=18 years had histologically confirmed, inoperable, previously untreated, measurable mCRC. Patients received irinotecan 180 mg m(-2) on day 1, oxaliplatin 100 mg m(-2) on day 15 and UFT 250 mg m(-2) plus LV 90 mg on days 1-21 every 28 days. The phase I/II study comprised 45 patients, 29 at the maximum tolerated dose (MTD). The response rate in 38 evaluable patients was 63% (95% confidence interval (CI): 49-80). Median time to progression and overall survival were 8.7 months (95% CI: 7.9-10.4) and 16.8 months (95% CI: 9.6-25.3), respectively. In the MTD group, one patient had grade 3 leucopenia; one had grade 3 neutropaenia; three had grade 3 diarrhoea; and one had grade 3 neurotoxicity. No hand-foot syndrome grade >1 was seen. In total, 67% of eligible patients received second-line therapy. UFT plus LV with alternating irinotecan and oxaliplatin is an efficacious first-line treatment for mCRC, with minimal neurotoxicity and hand-foot syndrome.     

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.     

热疗同CapeOx化疗治疗晚期结直肠癌临床研究

背景与目的:结直肠癌是消化道最常见的恶性肿瘤,其中复发转移是晚期结直肠癌患者致死的主要原因.利用热疗联合CapeOx化疗(卡培他滨联合奥沙利铂)治疗晚期结直肠癌,探索热疗与化疗联合的协同增效作用,以便通过多学科治疗方法进一步提高晚期结直肠癌的临床疗效.方法:采取随机方法将入组晚期结直肠癌病例分成研究组和对照组,研究组接受热疗和CapeOx化疗,对照组给予单纯CapeOx化疗.化疗方案为奥沙利铂130 mg/m2,第1天,卡培他滨1 000/m2,每天2次,口服连续14 d,3周为1个疗程.研究组在化疗的第1、5、10天接受肿瘤局部区域热疗,温度43℃,持续60 min.结果:研究组24例晚期结商肠癌患者中PR 14例,RR 58.3%.对照组2960中PR 9例,RR 31.0%,两组差异有显著性(P＜0.05).研究组和对照组患者的中位PDF分别为6.5个月(95%CI:4.4～8.6个月)、5.6个月(95%CI:4.6～6.3个月),两组间差异有显著性(P＜0.05).常见不良反应为周围神经异常、胃肠道毒性、手足综合征和白细胞减少,但均较轻微. 结论:热疗对CapeOx治疗晚期结直肠癌有协同增效作用,能够提高近期缓解率和延缓疾病进展时间.     

吉西他滨联合奥沙利铂和左旋门冬酰胺酶治疗复发性或难治性非霍奇金淋巴瘤

目的:观察吉西他滨联合奥沙利铂(L-OHP)、左旋门冬酰胺酶(L-ASP)对复发性或难治性进展型非霍奇金淋巴瘤的疗效和不良反应。方法:吉西他滨1000mg/m2,d1,d8,静脉滴注;L-OHP 80mg/m2,d1,d8,静脉滴注;L-ASP 1000 u/d,d1-d8静脉滴注。3-4周为一个化疗周期。20例复发性或难治性进展型非霍奇金淋巴瘤患者,疗程不少于3个周期。结果:20例患者中,14例获得缓解,占77.8%。其中完全缓解(CR)6例,部分缓解(PR)8例。6例具有B类症状的患者中,4例症状消失,1例明显改善,1例无改善。化疗不良作用主要为轻度的胃肠道反应,极少数患者出现严重的骨髓抑制。结论:吉西他滨联合L-OHP、L-ASP对复发性或难治性进展型非霍奇金淋巴瘤有较好的近期疗效,能明显改善患者症状,且大部分患者可以承受其不良反应,是一个值得进一步验证的补救性化疗方案。     

Gemcitabine (GEM) plus oxaliplatin, folinic acid, and 5-fluorouracil (FOLFOX-4) in patients with advanced gastric cancer

Background and aims: oxaliplatin in combination with folinic acid (FA) and infusional 5-fluorouracil (5-FU) has shown significant anti-tumor activity in gastric cancer patients (FOLFOX). Previous studies have shown that gemcitabine (GEM), a new fluorinated anti-metabolite, enhances the individual anti-tumor activity of either 5-FU or oxaliplatin. We have therefore designed a multi-center phase II trial in order to test a novel GEM + FOLFOX-4 regimen in patients with metastatic gastric cancer. Methods: we enrolled 36 patients, 28 males and 8 females, with an average age of 64.4 years (range 37–78), who received bi-weekly treatment with GEM (1,000 mg/m² on day 1), levo-FA (100 mg/m² on days 1 and 2), a 5-FU (400 mg/m²) bolus injection followed by 22-h continuous infusion (800 mg/m²) on days 1 and 2, and oxaliplatin 85 mg/m² in a 4–6 h intravenous (i.v.) infusion before the second FUFA administration on day 2. Results: the most frequent side effect was grade 1–2 hematological toxicity and late sensorial neurotoxicity. Two patients developed hypersensitivity to oxaliplatin while another developed an aseptic eosinophilic pneumonitis. Two patients refused to continue the treatment after two cycles of chemotherapy and were lost at the follow-up. Among the remaining 34 patients four achieved a complete response, 15 a partial response, 12 had a stable disease and three progressed. Conclusions: these results may grant the rationale to evaluate this multi-drug combination in randomized phase III trials in advanced gastric cancer.     

XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer.

PURPOSE: Capecitabine has demonstrated high efficacy as first-line treatment for metastatic colorectal cancer (MCRC). Oxaliplatin shows synergy with fluorouracil (FU), with little toxicity overlap. The XELOX regimen (capecitabine plus oxaliplatin), established in a previous dose-finding study, should improve on infused oxaliplatin with FU and leucovorin (FOLFOX) regimens. The present studies further characterize efficacy and safety of the XELOX regimen. PATIENTS AND METHODS: The antitumor activity of XELOX was investigated in a colon cancer xenograft model. Patients with MCRC received first-line XELOX in 3-week treatment cycles: intravenous oxaliplatin 130 mg/m(2) (day 1) followed by oral capecitabine 1,000 mg/m(2) twice daily (day 1, evening, to day 15, morning). RESULTS: A preclinical study confirmed that capecitabine has supra-additive activity with oxaliplatin. In the clinical study, 53 of 96 patients (55%) achieved an objective response, and 30 (31%) experienced disease stabilization for >/= 3 months following treatment. After 24 months' minimum follow-up, median time to disease progression (TTP) and median overall survival were 7.7 and 19.5 months, respectively. XELOX safety was predictable and similar to the FOLFOX4 regimen, except that myelosuppression was uncommon with XELOX (grade 3 or 4 neutropenia, 7%). Most adverse events were mild to moderate, the most common being acute sensory neuropathy (85%). Sixty-day, all-cause mortality was 2%. CONCLUSION: XELOX is a highly effective first-line treatment for MCRC. Response rates, TTP, and overall survival are similar to those observed with FU/leucovorin/oxaliplatin combinations. XELOX provides a more convenient regimen, likely to be preferred by both patients and healthcare providers. Capecitabine has the potential to replace FU/LV in combination with oxaliplatin for MCRC.