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。     

Weekly high-dose 5-fluorouracil as 24-h infusion and folinic acid (AIO) plus irinotecan as second- and third-line treatment in patients with colorectal cancer pre-treated with AIO plus oxaliplatin

Our objective was to evaluate the efficacy and safety of high-dose 5-fluorouracil (5-FU) as a 24-h infusion and folinic acid (FA) (AIO regimen) plus irinotecan (CPT-11) after pre-treatment with AIO plus oxaliplatin (L-OHP) in colorectal carcinoma (CRC). Twenty-six patients with non-resectable distant CRC metastases were analyzed for second- or third-line treatment with AIO plus CPT-11 after pre-treatment with AIO plus L-OHP. On an outpatient basis, the patients received a treatment regimen comprising weekly 80 mg/m2 CPT-11 in the form of a 1-h i.v. infusion and 500 mg/m2 FA as a 1- to 2-h i.v. infusion, followed by 2000 mg/m2 5-FU i.v. administered as a 24-h infusion once weekly. A single treatment cycle comprised six weekly infusions followed by 2 weeks of rest. A total of 26 patients received 344 chemotherapy applications with AIO plus CPT-11. The main symptom of toxicity was diarrhea (NCI-CTC toxicity grade 3+4) occurring in five patients (19%; 95% CI 7-39%). Nausea and vomiting presented in two patients (8%; 95% CI 1-25%). The response rate of 26 patients can be summarized as follows: partial remission: n=7 (27%; 95% CI 12-48%); stable disease: n=9 (35%; 95% CI 17-56%) and progressive disease: n=10 (38%; 95% CI 20-59%). The median progression-free survival (n=26) was 5.8 months (range 3-13), the median survival time counted from the treatment start with the AIO plus CPT-11 regimen was 10 months (range 2-24) and counted from the start of first-line treatment (n=26) was 23 months (range 10-66). We conclude that the AIO regimen plus CPT-11 is practicable in an outpatient setting and well tolerated by the patients. Tumor control was achieved in 62% of the patients. The median survival time was 10 months and the median survival time from the start of first-line treatment (n=26) was 23 months.     

Adding weekly irinotecan to high-dose 5-fluorouracil and folinic acid (HD-5-FU/FA) after failure for first-line HD-5-FU/FA in advanced colorectal cancer--a phase II study

Irinotecan (CPT-11) has been shown to prolong survival and improve quality of life in comparison to best supportive care in colorectal cancer patients with pretreatment of bolus 5-fluorouracil (5-FU). After first-line 24-h high-dose (HD) 5-FU/folinic acid (FA) an objective response rate of 11% with 3-weekly CPT-11 350 mg/m was reported. In the present study we investigated weekly CPT-11 in combination with 24-h HD-5-FU/FA as second-line treatment after prior exposure to 24-h HD-5-FU. Synergy between 5-FU and CPT-11 is the rationale to combine both substances for second-line therapy in order to overcome resistance to 5-FU. Thirty-five patients were recruited in a single institution to receive 6 x weekly CPT-11 80 mg/m(2), FA 200 mg/m(2) and 24-h HD-5-FU 2000 mg/m(2). Treatment was repeated on day 57. Patient characteristics: M/F=20/15, median WHO performance status 1, range (0-2). Thirty-four patients were evaluable for response: partial response 17% and no change 40%. Median time to progression and overall survival were 3.3 and 8.4 months, respectively. All patients were evaluable for toxicity analysis (National Cancer Institute Common Toxicity Criteria grade 3): leukocytopenia 3%, diarrhea 12% and vomiting/nausea 6%. Of the assigned doses, a median 100% of 5-FU and 92% of CPT-11 were administered during the first cycle of chemotherapy. We conclude that weekly CPT-11 and HD-5-FU/FA is an active and safe combination chemotherapy resulting in response rates in the upper range of other CPT-11-based second-line regimen. The toxicity profile in our series compared to 3-weekly CPT-11 seems favorable.     

草酸铂联合亚叶酸钙和5-氟脲嘧啶治疗晚期胃癌临床观察

目的 探讨草酸铂(L-OHP)联合亚叶酸钙(CF) 5-氟脲嘧啶(5-FU)方案治疗晚期胃癌近期疗效及其不良反应.方法 L-OHP 130mg/m2,静脉滴注3h,第d1;CF 100mg/m2,静脉滴注,第d1～5;5-FU150mg/m2,用CF之后静脉推注,同时5-FU 345mg/m2,静脉滴注,6～8 h,第d1-5,21d重复.结果 48例晚期胃癌患者,获CR 5例(10.4%),PR 24例(50%),SD 11例(22.9%),PD 8例(16.7%),总有效率(CR PR)达60.4%,主要不良反应为恶心、呕吐、白细胞和血小板降低及轻度周围神经毒性.结论 L-OHP联合CF 5-FU方案一线治疗晚期胃癌具有较好的疗效和安全性.     

伊立替康联合5-FU/CF治疗转移性结直肠癌46例

目的：评价伊立替康（CPT—11）联合5-FU／CF方案治疗FOLFOX4或LV5FU2方案失败的结直肠癌的客观疗效，临床受益和不良反应。方法：用CPT—11联合5-FU／CF方案治疗晚期结直肠癌患者46例，采用2周方案，即CPT—11 180mg／m^2 iv d1，CF200mg／m^2 iv d1-2，5-FU400mg iv bolusd1，5-FU600mg／m^2 iv，22hd1—2，每2周重复。观察期3—6个月。结果：完全缓解0例，部分缓解18例（有效率39．13％），稳定20例（43．47％），进展8例（17．39％）。临床受益率82．6％（19／23）。临床反应评价有效者36例（78．86％），生活质量显著提高。结论：CPT-11联合5-Fu／CF方案可作为转移性结直肠癌的二线治疗。     

Phase I trial of gemcitabine (Gemzar), 24 h infusion 5-fluorouracil and folinic acid in patients with inoperable pancreatic cancer

Gemcitabine (Gemzar) has a significant impact upon survival and quality of life for patients with pancreatic cancer, compared with 5-fluorouracil (5-FU). This phase I study was initiated to define the recommended dose of 5-FU delivered as a 24 h infusion in combination with gemcitabine (1000 mg/m2) and folinic acid (200 mg/m2) in patients with inoperable pancreatic cancer, treated on an outpatient basis. Drugs were administered weekly for 4 weeks out of 6 weeks. Sixteen chemonaive patients (median age 59 years, range 51-66) were enrolled, 15 had stage IV and one stage III disease. The median Karnofsky performance score (KPS) was 70 (range 60-80). Six patients received 5-FU 750 mg/m2, eight received 5-FU 1000 mg/m2 and two received 5-FU 1250 mg/m2. The maximum tolerated dose of 5-FU was 1000 mg/m2. Hepatotoxicity was dose limiting. One patient who received 5-FU 1250 mg/m2 died as a result of hepatorenal failure. There was one partial response, nine patients had stable disease for more than 3 months and 13 patients had improved KPS. The median time to progressive disease was 31 weeks (range 5-50 weeks). A phase 11 trial is underway to further assess the activity of this combination at the recommended dose of 750 mg/m2 5-FU.     

Dramatic tumor response of bulky liver metastases following treatment with CPT-11 and a chronomodulated 4-day infusion of 5-fluorouracil, folinic acid and oxaliplatin every 2 weeks in a colorectal cancer patient

Three active antitumor agents, i.e. 5-fluorouracil (5-FU), oxaliplatin and CPT-11, are available for the treatment of advanced colorectal cancer (CRC) patients and have been successfully combined in two-drug regimens. Hence, CRC has become a chemosensitive disease, but the optimal combination of these agents in first-line treatment remains to be determined. We report the first case of the combination of CPT-11 with oxaliplatin, 5-FU and folinic acid (FA) as first-line chemotherapy for a patient with a pre-occlusive sigmoid adenocarcinoma and synchronous bulky liver metastases. CPT-11 was given at 125 mg/m2, prior to the start of a chronomodulated 4-day infusion of oxaliplatin 25 mg/m2/day, 5-FU 800 mg/m2/day and FA 300 mg/m2/day repeated every 2 weeks. The doses could be escalated to 150 mg/m2 for CPT-11 and 900 mg/m2/day for 5-FU. After six cycles of chemotherapy 70% reduction in tumor size was documented in the liver. The primary tumor was no longer detectable by barium enema. The toxicity included three episodes of grade 4 neutropenic fever, and two episodes of severe diarrhea and vomiting with dehydration. A cumulative grade 2 neurosensory toxicity was observed after six cycles. Following surgery of the primary tumor, because of the major hepatic tumor response and of the absence of extra-hepatic metastases, the patient might be registered for a liver transplantation program. This first report of combining the three active agents in CRC every 2 weeks led to a high dose intensity of each agent and was associated with a dramatic tumor response of a very advanced disease in a patient with already altered performance status. The antitumor activity in this patient suggests that a three-drug intensified regimen might be feasible and active. A prospective study appears warranted to further examine the efficacy and toxicity of this therapeutic approach, and to determine whether it may increase the fraction of advanced CRC patients becoming resectable. This aggressive chemotherapy program may contribute to a re-examination of the usefulness of liver transplantation in patients with metastatic CRC confined to the liver.     

Phase I/II study of irinotecan (CPT-11) and S-1 in the treatment of advanced gastric cancer

A phase I/II study to determine the recommended dose for combination therapy with CPT-11 (irinotecan hydrochloride) and S-1 (tegafur, gimestat and otastat potassium) for advanced or recurrent gastric cancer, and to assess the safety and efficacy of this therapy. In the phase I portion of the study, S-1 was administered from day 1 to 14 at a fixed dose approved in Japan (80 mg/m2/day), and CPT-11 was administered on days 1 and 8, with its dose being escalated to 100 from 80 mg/m2. This regimen was repeated at 3-week intervals. The phase II portion of the study assessed the efficacy and safety of this regimen at the recommended dose determined in the phase I portion of the study. Seven patients were enrolled in the phase I portion of the study. The dose-limiting toxicity was the delay of administration owing to adverse reactions (leucopenia and diarrhea). The maximum tolerated dose of CPT-11 was 100 mg/m2 and the recommended dose was determined to be 80 mg/m2. In the phase II portion of the study, 10 patients with no prior chemotherapy regimen were enrolled. The median number of treatment cycles given was 4.5, the response rate was 20.0% (2/10) in all patients, the tumor control rate stable disease or better response was 60% (6/10) and the mean survival time was 311 days. Major adverse reactions included a decreased hemoglobin level, diarrhea, nausea and anorexia of grade 3 or worse (each occurred in 10% of the patients). Other adverse reactions were slight and well tolerated. The present combination therapy with CPT-11 and S-1 produced a low response rate but a high tumor control rate (stable disease or better response) and slight prolongation of survival time. This is a well-tolerated ambulatory regimen for advanced gastric cancer.     

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.     

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.     

Phase I trial of sequential raltitrexed followed by bolus 5-fluorouracil in patients with advanced colorectal cancer

Our objective was to determine the maximum tolerated dose (MTD) of sequential raltitrexed (Tomudex) and 5-fluorouracil (5-FU) by bolus administration every 3 weeks in patients with advanced colorectal cancer (aCRC) and appendiceal adenocarcinoma. This phase I dose-escalation study was carried out in three stages: (1) 5-FU fixed at 900 mg/m, raltitrexed escalated from 0.5 to 3.0 mg/m, (2) raltitrexed fixed at 3.0 mg/m, 5-FU escalated from 900 mg/m until dose-limiting toxicity (DLT) and (3) 5-FU fixed at the dose level below DLT, raltitrexed escalated from 3.0 mg/m until MTD. Seventy-one patients with measurable disease were enrolled. No DLTs were observed during stage 1 of treatment. At a fixed dose of raltitrexed 3.0 mg/m, DLT developed when 5-FU was increased to 1350 mg/m (stage 2). When 5-FU was fixed at 1200 mg/m and raltitrexed was increased to 6.0 mg/m (stage 3), DLT was dose limiting. The recommended doses for further study are 5.5 mg/m ralitrexed and 1200 mg/m 5-FU. Of the 69 patients evaluated for efficacy, one had a complete response (8.0 months) and five had partial responses (5.1-11.6 months). Thirty patients had stable disease for 5 or more cycles of therapy (mean time to progression: 3.6 months). Median survival was 11.7 months. We conclude that raltitrexed can be combined with bolus 5-FU, at raltitrexed doses that are higher than the recommended single-agent dose of 3.0 mg/m, with manageable toxicity. This combination shows encouraging activity, and survival appears promising in the pre-treated aCRC patient population. Further clinical trials are warranted.     

A Phase I Trial of Daily Oral 4′-N-Benzoyl-Staurosporine in Combination with Protracted Continuous Infusion 5-Fluorouracil in Patients with Advanced Solid Malignancies

PURPOSE: 4'- N -Benzoyl-staurosporine (PKC412) is an orally available staurosporine derivative that inhibits protein kinase C. The objectives of this phase I trial were to determine the maximum tolerated dose (MTD), the dose limiting toxicities (DLTs), and the pharmacokinetics of PKC412 when co-administered with 5-Fluorouracil (5-FU). EXPERIMENTAL DESIGN: PKC412 was given daily with a 21-day continuous i.v. infusion of 5-FU 200 mg/m2/day, repeated every 4 weeks. The PKC412 dose was escalated by a modified continual reassessment method. The steady-state plasma pharmacokinetics of 5-FU, PKC412, and two of its circulating metabolites were determined during the first cycle of therapy. RESULTS: A total of 33 patients were treated with 70 cycles (median: 2, range: 1-4) of PKC412 at doses ranging from 25 to 225 mg/day. No significant toxicities were encountered with doses up to 150 mg/day. Among nine patients treated with 225 mg/day of PKC412, one experienced grade 3 fatigue and nausea, another developed grade 3 hyperglycemia, and three had grade 2 emesis and stomatitis, leading to early treatment discontinuation. Minor responses consisting of a 40-45% tumor reduction were observed in two patients, one with gall bladder carcinoma and one with breast cancer. Mean values of steady-state pharmacokinetic variables for both PKC412 and 5-FU were comparable to single agent studies. CONCLUSIONS: The recommended phase II dose of PKC412 is 150 mg/day when combined with a continuous infusion of 200 mg/m2/day 5-FU. The dose limiting toxicity was grade 2 emesis and stomatitis and the regimen showed indications of activity. There was no evidence of a pharmacokinetic interaction between the two drugs.     

Assessment of Drug–drug Interaction and Optimization in Capecitabine and Irinotecan Combination Regimen using a Physiologically Based Pharmacokinetic Model

Capecitabine and irinotecan (CPT-11) combination regimen (XELIRI) is used for colorectal cancer treatment. Capecitabine is metabolized to 5-fluorouracil (5-FU) by three enzymes, including carboxylesterase (CES). CES can also convert CPT-11 to 7-ethyl-10-hydroxycamptotecin (SN-38). CES is involved in the metabolic activation of both capecitabine and CPT-11, and it is possible that drug–drug interactions occur in XELIRI. Here, a physiologically based pharmacokinetic (PBPK) model was developed to evaluate drug–drug interactions. Capecitabine (180 mg/kg) and CPT-11 (180 mg/m²) were administered to rats, and blood (250 μL) was collected from the jugular vein nine times after administration. Metabolic enzyme activities and K_i values were calculated through in vitro experiments. The plasma concentration of 5-FU in XELIRI was significantly decreased compared to capecitabine monotherapy, and metabolism of capecitabine by CES was inhibited by CPT-11. A PBPK model was developed based on the in vivo and in vitro results. Furthermore, a PBPK model-based simulation was performed with the capecitabin dose ranging from 0 to 1000mol/kg in XELIRI, and it was found that an approximately 1.7-fold dosage of capecitabine was required in XELIRI for comparable 5-FU exposure with capecitabine monotherapy. PBPK model-based simulation will contribute to the optimization of colorectal cancer chemotherapy using XELIRI.     

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.     

5-fluorouracil as a protracted continuous infusion plus irinotecan (CPT-11) in patients with advanced colorectal cancer treated with fluoropyrimidine-based regimens as first line

We carried out a single-center series with the combination of irinotecan (CPT-11) plus protracted 5-fluorouracil (5-FU) infusion as second-line chemotherapy for patients previously treated with a single-agent fluoropyrimidine as monotherapy or in combination with oxaliplatin. Twenty-five patients diagnosed with advanced colorectal cancer (CRC) received CPT-11 300 mg/m2 every 3 weeks plus 5-FU 250 mg/m2/day as a protracted infusion. Results were as follows. Twenty-four of 25 patients were evaluable for response. Two patients achieved a complete response and five a partial response, resulting in an overall response rate of 28%. Disease stabilization was obtained in 10 patients (40%), resulting in a tumor growth control rate of 68% (17 patients) and disease progression in seven (28%). Median progression-free interval was 6 months and median overall survival was 12 months. Neutropenia and diarrhea appeared as the most frequent adverse events, being grade 3/4 in 12 and 16% of patients, respectively. Mucositis, emesis, and hand and foot syndrome were mild. We conclude that protracted 5-FU infusion plus CPT-11 is an active and safe regimen for patients with advanced CRC. A phase III trial comparing this schedule with conventional CPT-11 monotherapy is warranted.     

奥沙利铂联合氟尿嘧啶/亚叶酸钙一线治疗转移性大肠癌2周方案与3周方案的对比研究

目的：比较奥沙利铂（L-OHP）联合5-氟尿嘧啶/亚叶酸钙（5-FU/CF）的2周方案与3周方案一线治疗转移性结直肠癌的临床疗效及不良反应。方法：66例转移性结直肠癌患者随机接受治疗。A组,予L-OHP85mg/m^2,第1天,静脉滴注2h,同时或之后予CF200mg/m^2,静脉滴注2h,续5-FU400mg/m^2,静脉推注,600mg/m^2持续静脉滴注22h,次日重复CF与5-FU。每2周重复1次,每2次计为1周期。B组,予L-OHP130mg/m^2,第1天,静脉滴注2h,CF200mg/m^2,静脉滴注2h,续5-FU375-425mg/m^2静脉滴注4-6h,连用5d,每3周重复1次,每次计为1周期。结果：A、B两组疗效相近,RR分别为42.9%和38.7%（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、神经系统毒性和脱发。结论：L-OHP联合5-FU/CF的2周方案与3周方案均可作为晚期转移性大肠癌一线治疗的选择之一。     

周剂量CPT-11治疗FOLFOX治疗失败的转移性结直肠癌

目的观察和评价依立替康(CPT-11)联合5-FU/LV治疗FOLFOX治疗失败的转移性结直肠癌的疗效及不良反应。方法入组患者共34例为转移性结直肠癌,经草酸铂及5-FU/LV治疗失败后,予CPT-11 60mg/m2,LV100mg/m2,5-FU 500mg/m2,每周1次,连续3周,每4周重复。患者最多接受6个周期,每例至少2周期化疗后评价疗效。结果全组34病例均可评价。PR为5例,SD为17例,有效率14.7%(95%可信区间3.6%～34.4%),疾病控制率64.7%(95%可信区间46.8%～85.6%),平均TTP为3.5个月(范围1.5～7.5个月)。主要不良反应为白细胞减少,恶心呕吐,手足综合征及延迟性腹泻,其不良反应发生率分别为67.4%(23/34),61.8%(21/34),64.8%(22/34),38.2%(13/34),均无IV度不良反应。结论周剂量伊立替康联合5-FU/LV为草酸铂治疗失败的转移性结直肠癌挽救治疗方案,不良反应轻微,适合于曾经强烈化疗患者。     

伊立替康联合氟尿嘧啶/亚叶酸钙治疗转移性结直肠癌

目的观察伊立替康联合亚叶酸钙及氟尿嘧啶方案治疗FOLFOX4方案失败的晚期结直肠癌的临床疗效及毒副反应。方法用CPT-11联合5-FU/CF方案治疗晚期结直肠癌患者28例,采用2周方案化疗,至少2个周期,即CPT-11180mg/m2静脉滴注,第1天;四氢叶酸200mg/m2静脉滴注,第1、2天;5-FU400mg/m2静脉推注,第1、2天;5-FU600mg/m2静脉滴注22h,第1、2天。按照WHO实体瘤近期客观疗效评定标准进行评价。结果全组28例患者均可评价疗效及不良反应。其中完全缓解0例,部分缓解10例,稳定9例,进展9例,有效率为35.7%。中位肿瘤进展时间TTP6.5个月,中位生存时间MST为12.5个月。不良反应主要是骨髓抑制,恶心、呕吐,脱发及延迟性腹泻。结论伊立替康联合5-FU/CF为二线治疗晚期结直肠癌安全有效的方案。     

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 II study of second-line oxaliplatin, irinotecan and mitomycin C in patients with advanced or metastatic colorectal cancer

The aim of this phase II study was to investigate the therapeutic value of second-line treatment with oxaliplatin, irinotecan (CPT-11) and mitomycin C (MMC) in patients with metastatic colorectal cancer pretreated with 5-fluorouracil (5-FU)-based chemotherapy. A total of 10 patients with metastatic colorectal cancer, all of whom had developed progressive disease from advanced or metastatic colorectal cancer while receiving or within 6 months after discontinuing first-line chemotherapy with 5-FU and leucovorin, were entered in this study. At the time of relapse, cytotoxic chemotherapy consisting of oxaliplatin 80 mg/m2 plus CPT-11 80 mg/m2 given i.v. on therapeutic day 1, and MMC 6 mg/ m2 given i.v. on day 15, respectively, was initiated. Treatment courses were repeated every 4 weeks for a total of six courses unless there was prior evidence of progressive disease. The overall response rate was 30% with three partial responses for all 10 assessable patients. Two additional patients (20%) had stable disease and five patients (50%) progressed. The median overall survival duration has not been reached yet and is longer than 7.1 months (range 2-23.5+) from the beginning of second-line therapy. Four patients are currently alive with progressive disease. The tolerance of second-line treatment was generally mild to moderate and easy to treat. Our data suggest that the combination of oxaliplatin, CPT-11 and MMC in patients with metastatic colorectal cancer pretreated with 5-FU-based chemotherapy is feasible and has substantial antitumor activity. Further evaluation of this regimen seems warranted.