A phase II study of modified FOLFOX as first-line chemotherapy in advanced small bowel adenocarcinoma

This study aimed at assessing the efficacy and safety of biweekly oxaliplatin in combination with continuous infusional 5-fluorouracil and leucovorin (modified FOLFOX regimen) in patients with advanced small bowel adenocarcinoma (SBA). Thirty-three eligible patients with previously untreated SBA received 85 mg/m(2) of oxaliplatin intravenously over a 2-h period on day 1, together with 400 mg/m(2) of leucovorin over 2 h, followed by a 46-h infusion of 5-FU 2600 mg/m(2) every 2 weeks. All patients were evaluable for efficacy and toxicity. A median of nine cycles (range 3-18) was administered. The objective response rate was 48.5% [95% confidence interval (95% CI): 31-67%], with one complete response, 15 partial responses, 12 stable diseases, and five progressions. The median time to progression was 7.8 months (95% CI: 6.0-9.6) and the median overall survival was 15.2 months (95% CI: 11.0-19.4). Toxicity was fairly mild. Grade 3 toxicities included neutropenia (12.1%), thrombocytopenia (3.0%), nausea (6.1%), vomiting (3.0%), diarrhea (3.0%), peripheral neuropathy (9.1%), and fatigue (3.0%), and grade 4 toxicities occurred in none of the patients. The modified FOLFOX regimen is highly active and well tolerated as first-line chemotherapy for advanced SBA patients.     

A phase II trial of modified FOLFOX as first-line chemotherapy in advanced colorectal cancer

The objective was to evaluate the efficacy and toxicity of leucovorin plus 5-fluorouracil combined with oxaliplatin (modified FOLFOX regimen) every 2 weeks on previously untreated advanced colorectal cancer patients in the Chinese population. Fifty-one inpatients were enrolled to receive 85 mg/m oxaliplatin intravenously over a 2- h period on day 1, together with 400 mg/m2 leucovorin over 2- h, followed by a 46-h infusion of 5-fluorouracil at 2600 mg/m2 every 2 weeks. Treatment was given until progression or unmanageable toxicity ensued. In all, 51 patients received three or more oxaliplatin doses and a median of nine treatment cycles (range 3-16 cycles). Of the 51 eligible patients, two complete responses and 22 partial responses were observed for an overall response rate of 47.0% (95% confidence interval 35-64%). Median progression-free survival was 7.7 months (95% confidence interval 6.8-8.6) and median overall survival was 15.0 months (95% confidence interval 13.1-16.9). Toxicities were mild: five patients (9.8%) reported grade 3-4 neutropenia, 33 patients (64.8%) experienced grade 1-3 neurotoxicity and only six patients (11.8%) experienced grade 3 neurotoxicity. The leucovorin plus 5-fluorouracil combined with oxaliplatin (modified FOLFOX) regimen is active and well tolerated in patients with previously untreated advanced colorectal cancer in the Chinese population.     

Biweekly bolus 5-fluorouracil and leucovorin plus oxaliplatin in pretreated patients with advanced colorectal cancer: a dose-finding study

The primary objective of this study was to determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) for bolus 5-fluorouracil (5-FU) administered on a biweekly schedule and in combination with fixed doses of leucovorin (LV) and oxaliplatin. The secondary objectives were to evaluate the toxicity profile and antitumor activity of this regimen for pre-treated patients with advanced colorectal cancer. A total of 26 patients with documented fluoropyrimidine-resistant, advanced colorectal cancer were enrolled into this phase I study. Fixed dose of oxaliplatin (85 mg/m2) was delivered as an i.v. infusion over 2 h, followed by LV (20 mg/m2) and 5-FU bolus every 2 weeks. The starting dose of 5-FU was 600 mg/m2, which was then incremented by 100 mg/m2 for each dose level. The DLT was determined for the first two treatment cycles, while toxicity and efficacy were evaluated throughout treatment. Six dose levels were tested. The MTD of 5-FU was deemed to be 1000 mg/m2 since dose-limiting fatigue was noted for three of the five-patient cohort during the first two cycles of chemotherapy at dose level 6. The most frequent treatment-related toxicities during the study were neutropenia, vomiting, diarrhea, fatigue and neuropathy. In an intent-to-treat analysis, the objective response rate was 30.8% (95% confidence interval 11.8-49.8%) for the 26 patients. The combination of bolus 5-FU/LV and oxaliplatin every 2 weeks is a feasible and effective treatment at the recommended dosages. A phase II study, to more-precisely define activity and toxicity, is ongoing.     

奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期结直肠癌的疗效观察

目的探讨奥沙利铂、5-氟脲嘧啶和亚叶酸钙联合治疗晚期结直肠癌的疗效及不良反应。方法 40例晚期结直肠癌患者均采用奥沙利铂联合5-氟尿嘧啶和亚叶酸钙治疗,治疗方案为:奥沙利铂130mg/m2静脉滴注4h,第1天;亚叶酸钙200mg/m2静脉滴注2h,第1～5天(在静脉滴注5-氟尿嘧啶之前),5-氟尿嘧啶400mg/m2静脉滴注4～6 h,平均用药4周期,2周期后进行疗效评价。结果 40例晚期结直肠癌患者中,完全缓解(CR)4例(10%),部分缓解(PR)18例(45%),稳定(SD)10例(25%),进展(PD)8例(20%),总有效率(ORR)为55%。不良反应为厌食疲乏、皮肤色素沉着、神经毒性、手足综合症、腹泻、恶心呕吐、肝功损害、白细胞下降,多数患者能耐受。结论奥沙利铂联合5-氟尿嘧啶和亚叶酸钙治疗晚期结直肠癌的疗效肯定,毒副反应小,患者能耐受,值得推广。     

Phase II study of oxaliplatin in combination with continuous infusion of 5-fluorouracil/leucovorin as first-line chemotherapy in patients with advanced gastric cancer

This study was designed to determine the efficacy and safety of biweekly oxaliplatin in combination with infusional 5-fluouracil (5-FU) and leucovorin in patients with advanced gastric cancer (AGC). Fifty-five eligible patients with measurable or assessable M/AGC (median age 62 and 90% of patients presented with metastasis) received oxaliplatin (85 mg/m2) intravenous infusion for 2 h, followed by intravenous infusion of 5-FU (3000 mg/m2) and leucovorin (100 mg/m2) for 46 h every 14 days until the patient's disease was either in progression, unacceptable toxicity, patient's withdrawal or the investigators' decision to discontinue treatment. Of the 55 enrolled patients, 48 were evaluable for response. Three patients (5.4%) showed complete remission and 20 patients (36.4%) achieved partial response. The overall response rate was 47.9%. Nineteen patients (34.5%) had stable disease and six patients (10.9%) showed progressive disease. The median time to progression was 5.6 months and the median overall survival was 10.8 months. Grade 3/4 toxicities included leucopenia (12.7%), thrombocytopenia (5.4%), diarrhoea (3.6%) and vomiting (9.1%). Peripheral neuropathy was noted in 61.8% of the patients (grade 1/2: 54.5%; grade 3: 7.3%). Our study confirmed that the combination of oxaliplatin and continuous infusion of 5-FU/leucoverin without bolus 5-FU as first-line chemotherapy is active for patients with AGC and relatively safe with lower haematological toxicity.     

奥沙利铂联合亚叶酸钙及氟尿嘧啶治疗晚期大肠癌的临床分析

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

伊立替康联合草酸铂、5-氟尿嘧啶、亚叶酸钙治疗晚期胃癌的临床疗效

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

Multifractionated paclitaxel and cisplatin combined with 5-fluorouracil and leucovorin in patients with metastatic or recurrent esophageal squamous cell carcinoma

This study assessed the clinical activity and safety of twice-weekly paclitaxel and cisplatin combined with 5-fluorouracil and leucovorin (TP-HDFL) in patients with recurrent or metastatic esophageal squamous cell carcinoma. The regimen, composed of paclitaxel 35 mg/m 1-h intravenous infusion on days 1, 4, 8 and 11; cisplatin 20 mg/m 2-h intravenous infusion on days 2, 5, 9 and 12; and 5-flourouracil 2000 mg/m and leucovorin 300 mg/m 24-h intravenous infusion on days 5 and 12; repeated every 21 days. Forty-one patients (median age 51), 15 with de-novo metastatic disease and 26 with recurrent disease, were enrolled. Grades 3-4 neutropenia, leukopenia and diarrhea occurred in 37.8, 29.4 and 14.2% of cycles, respectively. One patient died of invasive fungal infection. Three complete responses, 13 partial response and 13 stable diseases were observed. The intent-to-treat response rate was 39.0% (95% confidence interval: 24-54). The median progression-free and overall survival were 6.3 and 8.9 months (range 1-50+), respectively. Twice-weekly TP-HDFL has the activity and toxicity profile similar to the previously reported same three-drug combination for advanced esophageal cancer.     

重组人血管内皮抑素联合化疗治疗进展期胃癌的初步研究

目的探讨应用重组人血管内皮抑素联合OLF方案化疗对进展期胃癌术后生活质量和生存期的影响。方法将68例进展期胃癌术后患者随机分为两组:化疗组34例,采用OLF方案,奥沙利铂130mg/m~2d1,甲酰四氢叶酸200mg/m~2d1-5,5-氟脲嘧啶400mg/m~2d1-5,3周为1个周期;靶向治疗组34例,化疗方案同化疗组并于每周期化疗第1天开始给予恩度7.5mg/m~2,静脉滴注,每日1次,连用14d为1个疗程,间歇7d,重复使用。结果两组1年生存率分别为79.4%、85.3%,差异无统计学意义(P>0.05);3年生存率分别为32.4%、52.3%,差异有统计学意义(P<0.05)。两组生活质量改善率分别为61.8%(21/34)、82.4%(28/34),差异有统计学意义(P<0.05)。结论进展期胃癌术后应用重组人血管内皮抑素联合化疗可提高患者生活质量,延长生存时间。     

Feasibility of gemcitabine and oxaliplatin in patients with advanced biliary tract carcinoma and a performance status of 2

The use of gemcitabine and oxaliplatin is well documented in selected patients with advanced biliary tract carcinoma (BTC), but little is known on the feasibility of systemic treatments in patients with a performance status (PS) of 2. We retrospectively examined the medical records of consecutive BTC patients with a PS of 2 receiving gemcitabine 1000 mg/m(2) plus oxaliplatin 100 mg/m(2) every 2 weeks from January 2003 to December 2011 in our institution. Body composition was analysed by computed tomography scan to detect sarcopenia. The primary evaluation criterion was safety. The secondary evaluation criteria were the response rate, progression-free survival (PFS) and overall survival (OS). Twenty-eight patients (median age: 63 years, range 41-83) received a total of 175 cycles (median per patient: 6, range 2-12). Ten patients (35.7%) had sarcopenia on the pretreatment computed tomography scan. The most frequent toxicities were thrombocytopenia (grades 2-4: n=4, 14.3%), peripheral neuropathy (grades 2-3: n=9, 32.1%) and cholangitis (n=4, 14.3%). The best response was a partial response in 10.7% of patients [95% confidence interval (CI): 0-22.2] and stable disease in 42.9% of patients. The median PFS and OS were 4.6 (95% CI: 2.5-6.3) and 7.5 (95% CI: 5.2-9.5) months, respectively. The median PFS and OS were significantly longer in patients without sarcopenia: 7.0 months (95% CI: 4.4-8.0) vs. 2.2 months (95% CI: 2.0-2.5), P less than 0.01, and 10.4 months (95% CI: 7.5-11.6) vs. 4.9 months (95% CI: 3.7-5.2), P less than 0.01, respectively. In our experience, gemcitabine-oxaliplatin was feasible and induced effective palliation in PS2 patients with advanced BTC. Further studies are warranted to confirm these findings.     

奥沙利铂联合化疗治疗晚期大肠癌临床疗效

目的 观察L-OHP联合5-FU、LV方案治疗晚期大肠癌的临床疗效和毒性反应,并比较2周方案与3周方案的临床价值.方法 95例晚期大肠癌患者,按照时间顺序随机分为：①治疗组1组（47例）,奥沙利铂（L-OHP）85 mg/m^2,静滴2 h,d1;亚叶酸钙（LV）,静滴2 h,d1、d2;5-氟尿嘧啶（5-Fu）400 mg/m^2于亚叶酸钙（LV）之后推注,接着5-氟尿嘧啶（5-Fu）600mg/m2,持续静脉点滴22h,d1、d2,每2w重复,至少6个疗程.②治疗2组（48例）： L-OHP130mg/m^2,静滴2h,d1;LV 200mg/m^2,静滴2 h,继用5-Fu 500mg/d,静滴4 h,d1～d5,每3w重复,至少4个疗程.两组化疗前30 min静注托烷司琼100 ml或阿扎司琼10 mg预防呕吐.结果 两组疗效相近,总有效率可达到46.8%和41.6%（P＞0.05）：两组病例不良反应发生率相似,主要表现为消化道反应、骨髓抑制和神经系统毒性和脱发（P＞0.05）;两组CEA和CA-199在治疗后均明显降低（P＜0.01）,但治疗后两组之间的比较差异无显著性（P＞0.05）;中位生存期和中位无进展生存期差异有显著性（P＜0.01）.结论 L-OHP联合LV、5-FU化疗治疗晚期大肠癌是相对有效、低毒性的化疗方案,并建议优先选择标准的2 w治疗方案.     

Overcoming resistance to chronomodulated 5-fluorouracil and folinic acid by the addition of chronomodulated oxaliplatin in advanced colorectal cancer patients

The addition of oxaliplatin (L-OHP) to a 5-fluorouracil (5-FU)/ leucovorin (FA) regimen was retrospectively evaluated in 35 consecutive advanced colorectal cancer patients after progression of disease. L-OHP, 25 mg/m2/day, was infused from 10.00-22.00 with a peak flow at 16.00 while 5-FU, 700 mg/m2/day and FA, 150 mg/m2/day of the I-form or 300 mg/m2/day of the racemic form, from 22.00 to 10.00 with a nocturnal peak at 4.00, for 5 days every 3 weeks in 24 patients and for 4 days every 2 weeks in the other 11. Diarrhea and sensitive neuropathy were the most relevant types of toxicity (17% of patients). An objective response was achieved in 8/35 patients (23%) [95% CL 9-37], stabilization in 15 patients (43%) which included five minor responses, and progression in 12. There was no relevant difference in quality of life assessed with the EORTC QLQ C30+3 questionnaire before and after treatment. Median duration of response and median progression-free survival were 6 months; median overall survival was 11 months. This retrospective study showed that it is possible to reverse resistance to chronomodulated 5-FU by adding chronomodulated L-OHP to the previous regimen; comparison with different schedules of this combination should be performed in order to identify the best tolerated and active regimen as second-line treatment of advanced colorectal cancer.     

奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗铂耐药复发卵巢癌初探

目的探讨奥沙利铂(L-OHP)联合氟尿嘧啶(5-FU)和亚叶酸钙(LV)治疗晚期复发性卵巢癌的临床效果。方法对6例铂耐药复发卵巢癌患者行L-OHP联合5-FU、LV方案化疗,每3周重复,观察其临床效果及毒副反应。结果疗效评定4例部分有效(PR),1例稳定(SD),1例进展(PD),毒副反应均不严重。结论奥沙利铂联合5-FU、LV治疗铂耐药复发卵巢癌有一定疗效,值得进一步研究。     

反应停联合FOLFOX方案治疗晚期消化道癌临床研究

目的：评价反应停联合FOLFOX方案治疗晚期消化道癌的近期疗效和毒副反应。方法：28例晚期消化道癌患者,先给予草酸铂（L-OHP）85mg/m2静脉点滴2hd1,亚叶酸钙（CF）200mg/m2静脉点滴2hd1-d2,随后5-氟脲嘧啶（5-FU）400mg/m2静脉推注,5-FU600mg/m2静脉点滴22hd1-d2,同时给予口服反应停200mg/Dd1-d10。2周重复,4周期后评价疗效。结果：全组28例,其中完全缓解（CR）2例（7.1%）,部分缓解（PR）16例（57.1%）,稳定（SD）4例（14.3%）,进展（PD）6例（21.4%）。总有效率（CR＋PR）64.3%。胃癌16例,11例有效,有效率68.8%。大肠癌12例,7例有效,有效率58.3%。毒副反应主要是恶心呕吐,白细胞减少,神经感觉毒性,无化疗相关死亡。结论：反应停联合FOLFOX方案治疗晚期消化道癌疗效肯定,毒副反应能耐受。     

Phase I dose-finding study of biweekly irinotecan in combination with fixed doses of 5-fluorouracil/leucovorin, gemcitabine and cisplatin (G-FLIP) in patients with advanced pancreatic cancer or other solid tumors

This phase I trial was initiated based on encouraging clinical data with 5-fluorouracil (5-FU)/leucovorin (LV), gemcitabine and cisplatin (G-FLIP) in the therapy of solid tumors. In this trial, G-FLIP has been modified to facilitate outpatient administration and to optimize sequence-dependent synergistic activity. Treatment consisted of biweekly (once every 14 days) cycles of sequential gemcitabine 500 mg/m, irinotecan per dose escalation schedule, bolus 5-FU 400 mg/m and LV 300 mg on day 1 followed by a 24-h 5-FU infusion 1500 mg/m, followed by cisplatin 35 mg/m on day 2. The irinotecan starting dose was 80 mg/m and escalated by 20 mg/m in cohorts of three patients until the maximum tolerated dose (MTD) was defined. Twenty-three patients were enrolled (13 men/10 women) with the following cancers: 11 pancreatic, five gallbladder, three squamous cell carcinoma of the head and neck, one hepatocellular carcinoma, one melanoma, one gastric, and one breast cancer. Median patient age was 63 years (range 44-78) and median Karnofsky performance status (KPS) was 80. Patients received a median of 8 cycles (range 1-16) over five irinotecan dose levels (80, 100, 120, 140 and 160 mg/m). Dose-limiting toxicity consisting of grade 3 nausea/vomiting despite aggressive anti-emetic therapy occurred in one patient at dose level 1 and three patients at dose level 3. Grade 3-4 hematological toxicities per patient consisted of thrombocytopenia (3%), anemia (6%), thrombosis (23%), neutropenia (16%) and neutropenic fever (10%). Of 18 patients evaluable for response, one complete response (pancreatic) and eight partial responses (three gallbladder, two pancreatic, two head and neck, and one breast) were attained. Seven patients had disease stabilization (five pancreatic, one hepatocellular and one gastric) for a median of 16 weeks (range 10-22). Median time to disease progression among all 23 patients enrolled to the phase I portion of the trial was 20.5 weeks (range 4-37). We conclude that G-FLIP is a novel outpatient chemotherapy regimen with acceptable toxicity at the maximum tolerated irinotecan dose of 120 mg/m. The phase II trial of G-FLIP using an irinotecan dose of 120 mg/m for patients with metastatic pancreatic cancer is ongoing.     

多西紫杉醇联合奥沙利铂治疗进展期胃癌87例临床分析

目的评估多西紫杉醇联合奥沙利铂治疗进展期胃癌的效果和安全性。方法130例进展期胃癌患者随机分为实验组87例,对照组43例,实验组给予多西紫杉醇50mg／m^2静脉滴注,第1—3天;奥沙利铂65mg／m^2静脉滴注,第1天;氟脲嘧啶（5-Fu）500mg／m^2静脉滴注,第1～5天;亚叶酸钙（CF）300mg,第1～5天,在5-Fu之前2h静脉滴注。对照组用奥沙利铂130mg／m^2静脉滴注,第1天;5-Fu与CF的给药方法同实验组。3周为1个周期,治疗2个周期后评价疗效。结果实验组近期疗效、组织学变化、影像学变化等与对照组比较,差异均有统计学意义（均P〈0．05）。两组在白细胞减少、血小板减少、消化道反应、肝肾功能损害等不良反应方面比较,差异无统计学意义（均P〉0．05）。结论多西紫杉醇联合奥沙利铂化疗方案治疗进展期胃癌安全、有效。     

A phase I study of gemcitabine, 5-fluorouracil and leucovorin in patients with advanced, recurrent, and/or metastatic solid tumors

INTRODUCTION: This was a dose escalation phase I trial designed to establish the MTD (maximum tolerated dose) and toxicity profile of the combination of gemcitabine, leucovorin and 5-fluorouracil (5-FU). METHODS: Standard eligibility criteria were required for patients with advanced malignancy to enroll. Gemcitabine was escalated from an initial dose of 800 mg/m2. Gemcitabine was administered prior to leucovorin (25 mg/m2) followed by bolus 5-FU (600 mg/m2) every week for 3 weeks followed by 1 week of rest. RESULTS: Of 21 patients enrolled, 20 were eligible for MTD determination. Patients received a median of three 4-week cycles of chemotherapy (range: 1 to 8 cycles). Toxicity was predominantly hematologic or gastroenterologic. Four dose levels were studied. At a gemcitabine dose of 1,500 mg/m2 systemic symptoms of fatigue accompanied hematologic toxicity and patients refused further therapy. At 1,250 mg/m2, full dose intensity was not delivered during the first cycle in 7 of 8 patients treated. Therefore, 1,000 mg/m2 was established as the recommended phase II dose for gemcitabine in this study. Antitumor activity was seen at all dose levels. CONCLUSIONS: The combination of gemcitabine, leucovorin and 5-FU was tolerable at full doses of all 3 drugs with an expected toxicity profile. Recommended phase II dose for gemcitabine was 1,000 mg/m2. Initial evidence of clinical activity was seen in a variety of tumor types.     

草酸铂联合亚叶酸钙氟脲嘧啶治疗晚期胃癌的临床观察

目的：观察草酸铂联合亚叶酸钙、氟脲嘧啶治疗晚期胃癌的临床疗效和不良反应。方法：草酸铂85mg／m。静脉滴注2小时，第一天，亚叶酸钙200mg／m^2静脉滴注2小时，第一-二天，氟脲嘧啶600mg／m^2。静脉注射、900mg／m^2静脉滴注第一-二天，每2周重复。结果：53例患者中完全缓解（CR）3例、部分缓解（PR）11例、稳定（SD）5例、进展（PD）8例，总有效率CR＋PR14例（51．85％）。毒性反应主要为外周神经损害、恶心和呕吐、手足综合征。结论：草酸铂联合亚叶酸钙、氟脲嘧啶治疗晚期胃癌的临床疗效好、毒性反应可以耐受。     

A phase II pilot study of high-dose 24-hour continuous infusion of 5-FU and leucovorin and low-dose PALA for patients with colorectal cancer: A Southwest Oncology Group study

PURPOSE: The purpose of this phase II multi-institutional study was to define the efficacy and toxicity of infusional 5-FU in combination with PALA and leucovorin in patients with advanced colorectal cancer. PATIENTS AND METHODS: Patients were required to have histologically confirmed colorectal cancer with distant metastases. The treatment regimen consisted of 5-FU 2600 mg/m(2) as a 24-hours continuous infusion given once a week, concurrently with leucovorin (LV) at 500 mg/m(2) as a 24-hour continuous infusion. PALA was administered 24 hours prior to 5-FU/LV at a dose of 250 mg/m(2) iv over 15 minutes weekly. Patients were continued on the assigned treatment regimen until progression of disease, unacceptable toxicity, or the patient declined further therapy. RESULTS: This study accrued 28 patients and all were eligible and evaluable for toxicity. Four patients had inadequate assessment of response and are considered non-responders. There was one complete response and five partial responses for an overall response rate of 6/28 or 21% (95% confidence interval 8-41%). Estimated median survival was 17.4 months (95% confidence interval 13.3-20.5 months). One patient died of a treatment related infection. This patient also had grade 4 diarrhea and vomiting. CONCLUSION: The combination of 5-FU, leucovorin, and PALA in the doses and schedule used here, produces a response rate similar to other modulated schedules of 5-FU with similar survival and toxicity profiles.     

Induction chemotherapy with docetaxel, cisplatin, fluorouracil and l-leucovorin for locally advanced head and neck cancers: a modified regimen for Japanese patients

Combination chemotherapy with docetaxel (T), cisplatin (P), fluorouracil (5-FU) and leucovorin has been reported to have major activity against squamous cell carcinoma of the head and neck (SCCHN) administered as a 4-day (TPFL4) or 5-day (TPFL5) regimen. The purpose of this study was to evaluate the efficacy and toxicity of a modified TPFL regimen (m-TPFL) for locally advanced SCCHN, consisting of a modified dosage with docetaxel, cisplatin, 5-FU and l-leucovorin (l-LV) designed for Japanese patients. Organ preservation of the primary tumor site was also assessed. Thirty-four Japanese patients with locally advanced SCCHN were eligible. Docetaxel was administered as a 1-h i.v. infusion at 48 mg/m2 on day 1; cisplatin, 24 mg/m2/day; 5-FU, 560 mg/m2/day and l-LV, 125 mg/body/day were delivered on days 1-4 by continuous i.v. infusion. This regimen was administered every 28 days. Patients who achieved a complete response (CR) after induction chemotherapy underwent radiation therapy alone. Ninety-one cycles were administered. The main hematological toxicity was neutropenia, classified as grade III or IV in 18.7% of cycles. The most common non-hematologic toxicities included anorexia, stomatitis and alopecia. The clinical overall response rate to m-TPFL was 88.2%, with 58.8% CRs and 29.4% partial responses. After definitive locoregional therapy, 25 of 34 patients were disease-free with preserved primary tumor site anatomy. Overall and progression-free survival rates at the 2-year follow-up are 92.8 and 75.3%, respectively. Our m-TPFL regimen designed for Japanese patients yielded excellent response rates with an acceptable toxicity profile in good-performance-status patients.