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1.
Recchia F Saggio G Nuzzo A Lalli A Lullo LD Cesta A Rea S 《British journal of cancer》2004,91(8):1442-1446
This multicentre phase II study was designed to evaluate the antitumour activity and toxicity of bifractionated camptothecin (CPT-11) and 5-fluorouracil/ leucovorin (5-FU/LV) in the treatment of patients with metastatic colorectal cancer (MCC) who had been pretreated with 5-FU/LV-oxaliplatin (FOLFOX regimen). In all, 35 patients were enrolled in a two-stage trial. Treatment consisted of two daily doses of CPT-11, 90 mg m2 administered over 90 min, followed by LV, 200 mg m2 administered over 2 h plus 5-FU 400 mg m2 as a bolus and 600 mg m2 as a 22-h continuous infusion administered with disposable pumps as outpatient therapy. Toxicity was closely monitored. Response was evaluated by computed tomography scans every 8 weeks. All 35 patients were assessable for toxicity and response to treatment. Seven patients had a partial response, giving an overall response rate of 20%; 11 patients had stable disease (31.4%) and 17 progressed (48.5%). The median progression-free survival was 7.1 months and median survival was 14 months. A total of 10 patients (30%) experienced grade 3-4 toxicity, including nausea (15%), diarrhoea (12%) and neutropenia (15%), while seven patients (21%) had grade 2 alopecia. The bifractionated bimonthly schedule of CPT-11 plus 5-FU/LV showed substantial antitumour activity and was well tolerated in this group of patients with a poor prognosis, pretreated with the FOLFOX regimen. 相似文献
2.
Mabro M Louvet C André T Carola E Gilles-Amar V Artru P Krulik M de Gramont A;GERCOR 《American journal of clinical oncology》2003,26(3):254-258
Irinotecan has shown activity in advanced colorectal cancer resistant to leucovorin and fluorouracil. Preclinical experiments on cell cultures and human tumor xenografts indicated potential synergy when combining irinotecan and fluorouracil. We designed a new regimen combining leucovorin, fluorouracil, irinotecan, and hydroxyurea (FOLFIRI-2) and conducted a phase II study to establish its efficacy and tolerance in advanced colorectal cancer refractory to fluorouracil and oxaliplatin. Treatment was repeated every 2 weeks and consisted of leucovorin 400 mg/m2 on day 1, immediately followed by 46 hours of continuous infusion of fluorouracil 2,000 mg/m2, irinotecan 180 mg/m2 on day 3, and hydroxyurea 1,500 mg the day before leucovorin, and on days 1 and 2. Treatment was continued until progression or limiting toxicity. Twenty-nine heavily pretreated patients entered the study. Five patients achieved an objective response (17%), and 12 obtained stabilization of disease or minor response (52%). Five patients failed to continue treatment (17%) because of toxicity or worsening condition. From the start of FOLFIRI-2 treatment, median progression-free survival was 4.1 months and median survival was 9.7 months. Grade III/IV National Cancer Institute-Common Toxicity Criteria toxicities were nausea 17%, diarrhea 31%, mucositis 14%, neutropenia 52%, and febrile neutropenia 14%. FOLFIRI-2 achieved a good rate of response and stabilization in heavily pretreated patients despite significant toxicity. 相似文献
3.
Maindrault-Goebel F Louvet C André T Carola E Lotz JP Molitor JL Garcia ML Gilles-Amar V Izrael V Krulik M de Gramont A 《European journal of cancer (Oxford, England : 1990)》1999,35(9):1338-1342
For patients resistant to leucovorin (LV) and 5-fluorouracil (5-FU), the addition of oxaliplatin (85 or 100 mg/m2) to bimonthly LV-5-FU has given a response rate of 20-46%. The highest response rate has been observed with oxaliplatin 100 mg/m2 (FOLFOX2). The present phase II study (FOLFOX6) infused oxaliplatin (100 mg/m2) with LV (400 mg/m2) as a 2-h infusion on day 1, followed by bolus 400 mg/m2 and a 46-h infusion (2.4-3 g/m2) of 5-FU, every 2 weeks. Among the 60 patients treated, 16 (27%) had partial responses (95% confidence interval: 15-38), 27 (45%) had stable disease, 15 (25%) experienced disease progression and 2 (3%) had non-measurable disease. From the start of FOLFOX6, median progression-free survival was 5.3 months and median survival 10.8 months. From the 448 cycles analysed, NCI-CTC grade 3-4 toxicities per patient were: peripheral neuropathy 16%, nausea 7%, diarrhoea 7%, mucositis 5%, neutropenia 24%, thrombocytopenia 2%. Overall 26 (46%) patients experienced grade 3-4 toxicities. Because of toxicity, only 36% of the patients received > or = 90% of the scheduled oxaliplatin dose intensity. FOLFOX6 was active in pretreated patients resistant to LV-5-FU and is being investigated as first-line therapy. We are now investigating FOLFOX7, a regimen with a higher oxaliplatin dose intensity and a lower 5-FU dose. 相似文献
4.
Souglakos J Pallis A Kakolyris S Mavroudis D Androulakis N Kouroussis C Agelaki S Xenidis N Milaki G Georgoulias V 《Oncology》2005,69(5):384-390
PURPOSE: To evaluate the efficacy and tolerance of irinotecan (CPT-11) in combination with bolus and continuous infusion of 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFIRI regimen) as first-line treatment of elderly patients with metastatic colorectal cancer (MCC). METHODS: Thirty consecutive, previously untreated patients with metastatic colorectal cancer, aged (median 76 years; range 70-84) were enrolled. The performance status (WHO) was 0 in 8, 1 in 16 and 2 in 6 patients; 19 (63%) patients had prior surgery and 8 (27%) adjuvant chemotherapy. CPT-11 (180 mg/m(2) as a 90 min i.v. infusion) was administered on day 1, LV (200 mg/m(2) as a 2-hour i.v. infusion), 5-FU (400 mg/m(2)/d i.v. bolus followed by 600 mg/m(2)/d as a 22-hour i.v. continuous infusion) were given on days 1 and 2 every 2 weeks. RESULTS: Complete response was achieved in one (3.3%) patient and partial response in 10 (33.3%) (overall response rate: 36.6%; 95% C.I.: 26.6-48.4%); 11 (36.6%) patients had stable disease and, 8 (26.6%) disease progression. The median duration of response was 7.5 months and the median time to disease progression 7.0 months. After a median follow-up period of 17 months, the median overall survival was 14.5 months. Main toxicities were: grade 3-4 neutropenia (n = 6; 20%), grade 3 thrombocytopenia (n = 1; 3.3%), grade 2 anemia (n = 9; 30%), grade 3-4 diarrhea (n = 5; 17%) and grade 3 asthenia (n = 3; 10%). There was one treatment-related death due to neutropenic sepsis. CONCLUSIONS: The FOLFIRI combination is an active regimen with manageable toxicity as front-line treatment in patients above 70 years of age. 相似文献
5.
Hong-Liang Liang Ai-Ping Hu Sen-Lin Li Ji-Yong Liu 《Medical oncology (Northwood, London, England)》2014,31(6):1-4
Bevacizumab and panitumumab are human monoclonal antibodies with different targeting antigens, vascular endothelial growth factor, and epidermal growth factor receptor. This study examined the efficacy and safety of combining bevacizumab and panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) as the second-line therapy for patients with metastatic colorectal cancer (mCRC). Patients with mCRC, and previously failed with oxaliplatin-based chemotherapy, were given bevacizumab (3 mg/kg) and panitumumab (3 mg/kg) plus FOLFIRI every other week. From September 2008 to July 2012, 173 patients were included in the study. The response rate was 42.3 %, and the disease-controlled rate was 65.7 %. The median progression-free survival was 6.5 months, and the median overall survival was 15.4 months. Various adverse events (AE) including those known toxicities associated with antibody therapy were recorded. The overall AE rate was 64.5 % for grade 3–4. The treatment of combining bevacizumab and panitumumab plus FOLFIRI is effective and safe as a second-line therapy for patients with mCRC. 相似文献
6.
Background: FOLFOX2, a bimonthly regimen of high-dose leucovorin (LV), 48-hour continuous infusion of 5-fluorouracil (5-FU) (LV–5-FU) and oxaliplatin (100 mg/m2) produced a high response rate (46%; 95% confidence interval (95% CI): 31%–60%) in 5-FU pre-treated patients with metastatic colorectal cancer. In this phase II study, pre-treated patients were given a lower dose of oxaliplatin to reduce the toxic effects of the regimen.Patients and methods: Thirty patients with advanced colorectal adenocarcinoma and progression while receiving bimonthly LV–5-FU (LV: 500 mg/m2, 5-FU: 1.5–2 g /m2/ 22 hours, days 1–2, every two weeks), were given the same LV–5-FU schedule with the addition of oxaliplatin (85 mg/m2) every two weeks (FOLFOX3).Results: The main toxic effects were peripheral neuropathy (90%) with four severe sensitive neuropathies (WHO grade 2: 13%). The response rate was 20% (95% CI: 8%–39%). Median progression-free survival was 26 weeks, median survival was 57 weeks from the start of FOLFOX3 and median duration of the response was 37 weeks.Conclusions: Results obtained with FOLFOX3 confirmed the synergy between oxaliplatin and 5-FU in 5-FU-resistant metastatic colorectal cancer. However, the response rate seems to be lower than that obtained with FOLFOX2. Further studies to determine the best oxaliplatin dose intensity are in progress. 相似文献
7.
Reina JJ Aparicio J Salvador J Pica JM Rueda A Lorenzo A de la Puente CG Borrega P Moreno-Nogueira JA 《Cancer chemotherapy and pharmacology》2003,52(4):339-345
Purpose In this multicenter phase II study the efficacy and safety of the alternating schedule of irinotecan (CPT-11) with bolus 5-fluorouracil (5-FU) and leucovorin (LV) were assessed as first-line chemotherapy in patients with metastatic colorectal cancer (CRC).Patients and methods Enrolled in the study were 43 patients with advanced CRC. They received CPT-11 350 mg/m2 i.v. on day 1, alternating with LV 20 mg/m2 i.v. and 5-FU 425 mg/m2 i.v. daily for five consecutive days, on days 22–26 (Mayo Clinic regimen). One cycle consisted of 6 weeks.Results A total of 179 cycles were administered with a median of four per patient (range one to nine). Efficacy was analyzed on an intention-to-treat basis. The overall objective response rate was 30% (95% CI 16–44), with four complete responses and nine partial responses, whereas 20 patients (4%) showed stable disease. The median time to disease progression was 9.0 months and median survival was 18.5 months. Grade 3/4 diarrhea was mainly related to CPT-11 rather than to 5-FU (9.3% vs 4.7% of patients), whereas grade 3/4 neutropenia was higher during 5-FU administration (16.3% vs 7.0% of patients).Conclusions The alternating schedule of CPT-11 with 5 days bolus of 5-FU and low-dose LV showed a clinical benefit in terms of tumor growth control as first-line treatment of patients with metastatic CRC. The overall safety data confirmed this alternating combination as a well-tolerated treatment. 相似文献
8.
S Hegewisch-Becker Y Gruber A Corovic U Pichlmeier D Atanackovic A Nierhaus D K Hossfeld 《Annals of oncology》2002,13(8):1197-1204
BACKGROUND: Second- and third-line treatments remain a challenge in advanced colorectal cancer. Studies of bimonthly regimens of high-dose leucovorin (LV) and 5-fluorouracil (5-FU) by continuous infusion combined with oxaliplatin (L-OHP) have shown encouraging response rates in patients not responding to a bimonthly LV/5-FU regimen. Hyperthermic enhancement of L-OHP efficiency by increased DNA adduct formation has been demonstrated in vitro. This study was designed to address feasibility, toxicity and efficacy issues of whole-body hyperthermia (WBH) as an adjunct to L-OHP/LV/5-FU in pretreated patients after progression to first- and second-line treatments with LV/5-FU by continuous infusion and irinotecan. PATIENTS AND METHODS: Forty-four patients with advanced colorectal cancer, who had progressed during or within 3 months after completion of chemotherapy with LV/5-FU 24-h infusion (LV/5-FU(24h)) (eight patients) or irinotecan combined with or after LV/5-FU(24h )(36 patients), were treated with L-OHP 85 mg/m(2), 2-h intravenous (i.v.) infusion, followed by LV 200 mg/m(2), 1-h i.v. infusion, and 5-FU 3 g/m(2), 48-h continuous infusion. Every second cycle of the biweekly regimen was combined with WBH, thus allowing a comparison of toxicity with and without WBH in the same patient. Whole-body hyperthermia was administered by a humidified radiant heat device. The target temperature of 41.8 degrees C was maintained for 60 min. L-OHP (2-h infusion) was started at a core body temperature of 39 degrees C. RESULTS: All patients could be evaluated for toxicity, and 41 patients were evaluable for response. A total of 273 L-OHP-containing regimens were administered, 130 with and 143 without WBH. Hyperthermic treatment combined with L-OHP/LV/5-FU showed no unexpected toxicities. WHO grade 3 toxicities were rare and evenly balanced between cycles given with or without WBH. One early death occurred due to sepsis and tumor lysis. The overall response rate was 20%, with two complete and six partial responses. Twenty-three patients (56%) had stable disease and nine patients (22%) progressive disease. With a median observation time of 70 weeks, the median time to progression was 21 weeks [95% confidence interval (CI) 17-25 weeks] and the median survival was 50 weeks (95% CI 39-61 weeks) from the start of therapy. CONCLUSIONS: This trial suggests some advantage of combining L-OHP/LV/5-FU with WBH. Results compare favorably with the activity of similar regimens without WBH in less extensively pretreated patients. These data support further evaluation and warrant phase III studies. 相似文献
9.
F Maindrault-Goebel A de Gramont C Louvet T André E Carola V Gilles J P Lotz C Tournigand M Mabro J L Molitor P Artru V Izrael M Krulik 《Annals of oncology》2000,11(11):1477-1483
Background:studies of bimonthly 48-hour regimens of high-doseleucovorin (LV) (FOLinic acid), 5-fluorouracil (5-FU) by continuous infusioncombined with OXaliplatin (FOLFOX) in pretreated patients with metastaticcolorectal cancer suggest that oxaliplatin dose intensity is an importantprognostic factor for response rate and progression-free survival (PFS). Tohelp define the optimal dose schedule for oxaliplatin in pretreated metastaticcolorectal cancer, we retrospectively analyzed data from three phase IIstudies using different FOLFOX regimens (FOLFOX2, 3 and 6).
Patients and methods:Data on 126/161 patients were analyzed.FOLFOX2 included oxaliplatin 100 mg/m2; FOLFOX3, 85mg/m2; and FOLFOX6, 100 mg/m2 (added to a simplifiedLV–5-FU regimen), all as two-hour infusions. A total of 47 patientsreceived low dose intensity oxaliplatin (LDI: 85 mg/m2/2 weeks)and 79 patients high dose intensity oxaliplatin (HDI: >85mg/m2/2 weeks).
Results:Objective responses occurred in 31 (39%) HDIpatients and 9 (19%) LDI patients (P = 0.03). Median PFS was28 weeks, with 52% of HDI patients progression free at 6 months, and26 weeks with 36% of LDI patients progression free at six months(P = 0.02). Increased oxaliplatin dose intensity was not associatedwith increased neurotoxicity or other toxicities. FOLFOX are among the mosteffective regimens for treating LV–5-FU-resistant metastatic colorectalcancer.
Conclusions:This study shows that oxaliplatin doseintensification significantly improves response rate and PFS in pretreatedmetastatic disease without increasing severe toxicity. 相似文献
10.
Gennatas C Papaxoinis G Michalaki V Mouratidou D Andreadis C Tsavaris N Pafiti A 《Journal of chemotherapy (Florence, Italy)》2006,18(5):538-544
The purpose of this study was to compare the activity and toxicity of an irinotecan (CPT-11), leucovorin (LV) and 5-fluorouracil (5FU) combination with a standard regimen of 5FU and LV, in patients with advanced colorectal carcinoma. One hundred and sixty patients were randomized; 80 patients (group A) received LV 20 mg/m(2) bolus i.v. and 5FU 425 mg/m(2) bolus i.v. on days 1-5, every 28 days; 80 patients (group B) received CPT-11 80 mg/m(2) (30-90 min i.v. infusion), followed by LV 20 mg/m(2) bolus i.v. and 5FU 425 mg/m(2) bolus i.v. on days 1, 8, 15, 22, 29, and 36, every 8 weeks. The overall response rate was 30% and 47.5% in groups A and B respectively. Progression-free survival was significantly higher in the triple-drug combination arm (median 7.5 vs. 4.5 months; p= 0. 0335). However, overall survival did not differ significantly between the two arms (15 months vs. 14 months for the groups B and A respectively; p=0.3531). The main grade 3 adverse events were diarrhea (19%, in group A vs. 35% in group B; p=0.032) and mucositis (2% vs. 14%; p=0.017). The regimen containing irinotecan showed activity in advanced colorectal cancer. The overall safety data confirm this combination as a well-tolerated treatment. 相似文献
11.
Moehler M Eimermacher A Siebler J Höhler T Wein A Menges M Flieger D Junginger T Geer T Gracien E Galle PR Heike M 《British journal of cancer》2005,92(12):2122-2128
An open-label randomised comparison of efficacy and tolerability of irinotecan plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (ILF) with etoposide plus 5-FU/LV (ELF) in patients with untreated metastatic or locally advanced gastric cancer. One cycle of ILF comprised six once-weekly infusions of irinotecan 80 mg m(-2), LV 500 mg m(-2), 24-h 5-FU 2000 mg m(-2), and ELF comprised three once-daily doses of etoposide 120 mg m(-2), LV 300 mg m(-2), 5-FU 500 mg m(-2). In all, 56 patients received ILF and 58 ELF. Median age was 62 years, Karnofsky performance 90%, and disease status was comparable for both arms. The objective clinical response rates after 14 weeks treatment (primary end point) were 30% for ILF and 17% for ELF (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.29-1.13, P = 0.0766). Overall response rates over the entire treatment period for ILF and ELF were 43 and 24%, respectively (RR 0.56, 95% CI 0.33-0.97; P = 0.0467). For ILF and ELF, respectively, median progression-free survival was 4.5 vs 2.3 months, time to treatment failure was 3.6 vs 2.2 months (P = 0.4542), and overall survival was 10.8 vs 8.3 months (P = 0.2818). Both regimens were well tolerated, the main grade 3/4 toxicities being diarrhoea (18%, ILF) and neutropenia (57%, ELF). The data from this randomised phase II study indicate that ILF provides a better response rate than ELF, and that ILF should be investigated further for the treatment of metastatic gastric cancer. 相似文献
12.
Oliver F Bathe Scott Ernst Francis R Sutherland Elijah Dixon Charles Butts David Bigam David Holland Geoffrey A Porter Jennifer Koppel Scot Dowden 《BMC cancer》2009,9(1):156
Background
Chemotherapy may improve survival in patients undergoing resection of colorectal liver metastases (CLM). Neoadjuvant chemotherapy may help identify patients with occult extrahepatic disease (averting unnecessary metastasectomy), and it provides in vivo chemosensitivity data. 相似文献13.
Weekly irinotecan (CPT-11) in 5-FU heavily pretreated and poor-performance-status patients with advanced colorectal cancer 总被引:1,自引:0,他引:1
Benavides M García-Alfonso P Cobo M Muñoz-Martín A Gil-Calle S Carabantes F Villar E Graupera J Balcells M Pérez-Manga G 《Medical oncology (Northwood, London, England)》2004,21(3):255-262
Irinotecan (CPT-11) is an effective drug in patients with advanced colorectal cancer (CRC). Little is known about its efficacy
and safety in previously treated patients with poor performance status. We prospectively evaluated the antitumor efficacy
and safety of CPT-11 monotherapy in this setting. Thirty-four patients with poor performance status (Karnofsky score between
60 and 80) and/or progressing on one or more previous 5-FU-based chemotherapy lines for advanced colorectal adenocarcinoma
were enrolled in this study. Treatment consisted of irinotecan (CPT-11) at 100 mg/m2 administered as a 60-min iv infusion every week for four consecutive weeks followed by a 2-wk rest period until disease progression
or unacceptable toxicity. The overall objective response rate (WHO criteria) for the 34 patients included was 20.6% [95% confidence
interval (CI): 6.3%–34.9%]. Stable disease was obtained in 13 patients (38.2%) and 14 patients (41.2%) progressed. The median
time to disease progression was 5.5 mo (range: 0.9–17.5) and the median survival was 8.3 mo (95% CI: 1.7–16.9). Overall, weekly
CPT-11 was well tolerated with grade 3/4 neutropenia as the main hematological toxicity (11 patients: 32.4%; 14 infusions:
3.3%), and delayed diarrhea (10 patients: 29.4%; 16 infusions: 3.8%) as the main grade 3/4 non-hematological toxicity. In
conclusion, weekly CPT-11 at 100 mg/m2 for four consecutive weeks followed by a 2-wk rest period showed antitumor efficacy and may be safely administered to heavily
pretreated patients with advanced colorectal cancer and a poor performance status. Weekly CPT-11 monotherapy may be considered
as a therapeutic option for this population of patients. 相似文献
14.
Outpatient weekly high-dose continuous-infusion 5-fluorouracil plus oral leucovorin in advanced colorectal cancer. A phase II trial 总被引:1,自引:1,他引:1
Aranda E.; Cervantes A.; Carrato A.; Fern{acute}ndez-Martos C.; Anton-Torres A.; Massuti T.; Barneto I.; Garcia-Conde J.; Baron J. M; Diaz-Rubio E.; Spanish Cooperative Group For Gastrointestinal Tumor Therapy 《Annals of oncology》1996,7(6):581-585
BACKGROUND:: Background: In a previous phase III trial we showed thatmaximum tolerable dose (MTD) of 5-fluorouracil (5-FU) a weekly48-hour continuous infusion (CI) was 3.5 g/m2. In a subsequentconfirmative phase II trial with 85 evaluable patients, a 38.5%response rate was obtained, and a median survival of 12 months.These data were comparable to those achieved by biochemicalmodulation of 5-FU with leucovorin. On this basis we attemptedto modulate high-dose 5-FU (3 g/m2) with oral leucovorin (LV)but the regimen too toxic and the dose had to be reduced. Anew phase II trial with 2 g/m2/week plus oral leucovorin wasplanned. PATIENTS AND METHODS:: From July 1992 to June 1994, 110 previously untreated patientswith advanced, measurable colorectal cancer were included ina multicenter study. The patients received, on an outpatientbasis, 5-FU 2 g/m2 by continuous infusion for 48 hours oncea week until progression or the appearance of toxic effects.Oral leucovorin (60 mg every six hours) was also given duringthe 5-FU infusion. RESULTS:: Patients received a median dose intensity of 5-FU of 1.6 g/m2/week(range 0.92). Three complete responses and 36 partialresponses were observed. The overall response rate was 37.5%(95% CI, 28% to 46.8%), the median time to progression 7.4 monthsand median survival 14.5 months. W.H.O. grade 3 diarrhea occurredin 27 patients (24.5%); grade 3 mucositis was observed in 9(8.1%) patients and grade 4 in one. Grade 3 nausea and vomitingwas reported in 13 (11.7%) patients, while grade 3 hand-footsyndrome was detected in only 5 (4.5%). Grade 4 leukopenia occurredin one patient and grade 34 thrombocytopenia in two. CONCLUSION:: Oral leucovorin modulation of weekly 48-hour continuous infusionof 5-FU at 2 g/m2 is an active regimen, with diarrhea and mucositisas the main limiting toxic effects. Its antitumor activity doesnot seem superior to that obtained with a weekly 48-hour continuousinfusion of 5-FU alone at a dose of 3.5 g/m2. advanced colorectal cancer, biochemical modulation, continuous infusion, fluorouracil, phase II trial 相似文献
15.
16.
17.
Kono T Ebisawa Y Tomita I Chisato N Kamiya K Asama T Ayabe T Ashida T Kohgo Y Kasai S 《Journal of chemotherapy (Florence, Italy)》2005,17(2):224-227
Irinotecan combined with continuous-infusion 5-fluorouracil (5FU) has been shown to be an effective and tolerable regimen in the treatment of metastatic colorectal cancer (MCRC). Tegafur/uracil (UFT) during 5FU infusion enhances plasma 5FU concentration, mimics continuous 5FU infusion and delivers the drug to target tumor cells. We conducted a phase II trial of four-agent combined therapy for MCRC, giving patients (pts) intravenous irinotecan (30 mg/m2 on day 1), leucovorin (LV, 200 mg/m2 on day 1 and 2), 5FU (300 mg/m2 on day 1 and 2), and UFT (400 mg/day for 14 days). The main endpoint was the objective tumor response rate. Sixteen pts with a good performance status were enrolled from February 2001 to May 2002. The response rate was 19% (3 partial responses), and 13 pts had stable disease. The median time to progression was 5.2 months, and the median survival time was 20.2 months. Considering the low toxicity and reasonable cost, this regimen deserves further investigation. 相似文献
18.
19.
Jeeyun Lee Kyung Hae Jung Young Suk Park Joong Bae Ahn Sang Jun Shin Seock-Ah Im Do Youn Oh Dong Bok Shin Tae Won Kim Namsu Lee Jae Ho Byun Yong Sang Hong Joon Oh Park Se Hoon Park Ho Yeong Lim Won Ki Kang 《Cancer chemotherapy and pharmacology》2009,64(4):657-663
Background Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, anti-angiogenesis, and
apoptosis. This phase II trial evaluated the efficacy and toxicity profile of conventional FOLFIRI chemotherapy plus simvastatin
in metastatic colorectal cancer patients.
Methods Patients received irinotecan 180 mg/m2 as a 90-min infusion followed by leucovorin 200 mg/m2 in a 2-h infusion, and then 5-FU 400 mg/m2 bolus injection followed by 2,400 mg/m2 as a 46-h continuous infusion. Treatment cycles were repeated every 2 weeks until documented disease progression, unacceptable
toxicity, or patient’s refusal. Simvastatin 40 mg tablet was given once daily per oral everyday during the period of chemotherapy
without a rest.
Results From October 2005 to June 2006, 49 patients were enrolled. The overall response rate (ORR) was 46.9% (95% CI, 31.0–58.8) by
intent-to-treat analysis and 45.8% (95% CI, 33.3–62.8) by per-protocol analysis. There were one complete response (CR) and
22 partial responses (PRs). Both CR and PRs were confirmed at least 4 weeks later. The disease-control rate was 83.7% (95%
CI, 73.4–94.0). The median follow-up duration was 25.6 months (range, 20.9–28.8 months). The median survival of all patients
was 21.8 months (95% CI, 14.4, 29.2). The median TTP was 9.9 months (95% CI, 6.4, 13.3). No patients experienced additional
adverse effect that was definitely caused by simvastatin drug therapy in this trial.
Conclusion The combination of simvastatin plus FOLFIRI was a feasible regimen with promising antitumor activity. 相似文献
20.
Aranda E.; Valladares M.; Martinez-Villacampa M.; Benavides M.; Gomez A.; Massutti B.; Marcuello E.; Constenla M.; Camara J. C.; Carrato A.; Duenas R.; Reboredo M.; Navarro M.; Diaz-Rubio E. 《Annals of oncology》2009,20(2):251-257
Background: Irinotecan plus infusional 5-fluorouracil/leucovorin(FOLFIRI) is accepted as a reference treatment for the first-linetreatment of patients with metastatic colorectal cancer (MCRC).The aim of this study was to demonstrate that a regimen withoutleucovorin (LV) (FUIRI) is not inferior to the standard FOLFIRI(response rate). Patients and methods: Chemotherapy-naive patients with MCRCwere randomized to receive either irinotecan (180 mg/m2 on day1) + 5-fluorouracil (5-FU) (400 mg/m2 bolus and 600 mg/m2 22-hinfusion) + LV (200 mg/m2 on days 1–2) (FOLFIRI) every2 weeks or irinotecan (80 mg/m2) + 5-FU (2.250 mg/m2 48-h infusion)(FUIRI) weekly. Results: In all, 346 patients were included, 173 in each arm.In the intention-to-treat analysis, the response rates for FOLFIRIand FUIRI were 57% [95% confidence interval (CI) 49% to 64%]and 51% (95% CI 43% to 59%), respectively (P = 0.2809). No statisticallysignificant differences were observed between FOLFIRI and FUIRIregarding median progression-free survival (8.3 versus 8.4 months;P = 0.4339) nor median overall survival (21.6 versus 19.2 months;log-rank test P = 0.2941). Grade 3/4 neutropenia was significantlymore frequent on FOLFIRI arm (27% versus 9%), while the proportionof diarrhea was higher on FUIRI arm (21% versus 42%). Conclusion: FUIRI represents a valid alternative without LVto the FOLFIRI regimen as MCRC first-line treatment. Key words: colorectal cancer, 5-fluorouracil, irinotecan
Received for publication May 7, 2008. Revision received July 11, 2008. Accepted for publication July 14, 2008. 相似文献