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1.
Catalano V Vincenzi B Giordani P Graziano F Santini D Baldelli AM Alessandroni P Schiavon G Rossi D Casadei V D'Emidio S Luzi Fedeli S Tonini G Fiorentini G 《Gastric cancer》2012,15(4):419-426
Background
The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) has demonstrated a survival advantage over cisplatin and 5-FU, but with substantial hematological toxicity. We aimed to evaluate the efficacy and toxicity of a sequential regimen with cisplatin, leucovorin, and 5-FU (PLF) followed by docetaxel in metastatic gastric cancer patients.Methods
Treatment consisted of 4 cycles of biweekly PLF (cisplatin 50?mg/m2 as a 30-min infusion on day 1, leucovorin 200?mg/m2 in a 2-h infusion, and 5-FU 2,800?mg/m2 in a 48-h continuous infusion starting on day 1) followed, in cases of response or stable disease, by 3 cycles of docetaxel (75?mg/m2, every 3?weeks).Results
Thirty-four patients were enrolled, with an average age of 64?years (range 34–69). The main cumulative grade 3–4 toxicities were: neutropenia (38.2%), febrile neutropenia (11.8%), and fatigue (14.7%). After the planned 7 cycles of treatment, the overall response rate was 38.2% (95% confidence interval [CI] 21.9–54.6), with 3 complete and 10 partial responses. Median progression-free survival and overall survival were 4.8 and 10.6?months, respectively.Conclusions
For patients with metastatic gastric cancer, the sequential administration of cisplatin, leucovorin, 5-FU, and docetaxel may be an effective palliative option and offers a far more favorable toxicity profile than the simultaneous use of docetaxel, cisplatin, and 5-FU. 相似文献2.
Docetaxel, 5-fluorouracil, and leucovorin as treatment for advanced gastric cancer: results of a phase II study 总被引:4,自引:0,他引:4
Manuel Constenla Ramon Garcia-Arroyo Isabel Lorenzo Nancy Carrete Begoña Campos Patricia Palacios 《Gastric cancer》2002,5(3):0142-0147
Background: Previous studies have shown that the taxane, docetaxel, is effective in treating gastric cancer. The aim of this study was
to assess the efficacy and safety of docetaxel in combination with 5-fluorouracil (5-FU) and leucovorin (LV).
Methods: Thirty patients with histologically proven locally advanced and/or metastatic gastric cancer with WHO performance status
0–2 were enrolled and received either 75 or 100 mg/m2 docetaxel as a 1-h intravenous infusion on day 1 every 28 days. All patients also received 5-FU (1800 mg/m2) plus LV (500 mg/m2), by continuous intravenous infusion over 24 h on days 1, 8, and 15 every 28 days. Chemotherapy was given for at least two
cycles.
Results: Of the 25 evaluable patients, 3 showed a complete response, 4 showed a partial response, and 11 patients had stable disease.
The overall response rate was 28.0% (95% confidence interval [CI], 10.4, 45.6). The median time to progression was 5.9 months
(95% CI, 5.4, 6.5), and the median overall survival was 7.7 months (95% CI, 7.2, 8.3) for the intent-to-treat population.
The most frequent grade III and IV hematological toxicities were neutropenia and anemia. Febrile neutropenia was observed
in 10% of patients and 2.4% of cycles. The prophylactic use of granulocyte colony-stimulating factor (G-CSF) in 3 patients
reduced the incidence and severity of neutropenia. Other hematological toxicities were rare.
Conclusion: Docetaxel in combination with weekly 5-FU and LV is effective in treating patients with advanced/metastatic gastric cancer.
This new docetaxel-containing combination shows promise as a third-generation treatment option for gastric cancer.
Received: December 25, 2001 / Accepted: April 22, 2002
Offprint requests to: M. Constenla 相似文献
3.
Docetaxel and cisplatin in patients with advanced or recurrent gastric cancer: a multicenter phase I/II study 总被引:1,自引:0,他引:1
Yashushi Mitachi Yuh Sakata Atsushi Ohtsu Ichinosuke Hyodo Kenichi Katsu Motonori Sairenji Soh Saitoh Toshikazu Suwa Toshinobu Sato Yoshinori Miyata 《Gastric cancer》2002,5(3):0160-0167
Background: Because docetaxel and cisplatin are both active against gastric cancer and have different mechanisms of action, this combination
may provide additive or synergistic effects against gastric cancer. This article presents a phase I study designed to determine
the recommended dose of cisplatin combined with a fixed dose of docetaxel, and a subsequent phase II study that evaluated
the clinical efficacy and feasibility of this combination regimen.
Methods: Patients enrolled in the study had to have histologically confirmed advanced or recurrent gastric cancer with measurable
disease and adequate organ function, and to be aged 20 to 75 years, with a performance status (PS) of 0 to 2. In the phase
I study, docetaxel was administered at a fixed dose of 60 mg/m2 on day 1. Cisplatin was also administered on day 1, at dose levels of 60, 70, and 80 mg/m2. Where dose-limiting toxicities were not observed in more than 33.3% of patients, three patients were accrued for each dose
level.
Results: Recommended doses for the phase II evaluation were determined to be 60 mg/m2 of docetaxel and 80 mg/m2 of cisplatin. Although grade 3 or more severe leukopenia and neutropenia were observed in 71.4% and 82.1% of the patients,
respectively, nonhematological toxicities were not severe. The overall response rate at the recommended dose level was 25.0%
(7/28 patients), and the rate was 40% (6/15) for patients with liver metastases. The median survival time was 9.7 months and
the 1-year survival rate was 39.3%.
Conclusion: Although this study failed to demonstrate a high response rate, this regimen was feasible and might be of value in further
investigations in respect to the relatively high response rate in patients with liver metastasis and the favorable survival.
Received: March 26, 2002 / Accepted: June 28, 2002
Acknowledgments We are grateful to Drs. T. Taguchi, M. Yoshida, K. Nagao, and S. Yoshida for their helpful advice and N. Hirabayashi, W. Koizumi,
and K. Shirao for their extramural review during the study.
Offprint requests to: Y. Mitachi 相似文献
4.
Jaffer A. Ajani 《Gastric cancer》2002,5(1):31-34
Docetaxel is considered to be active in untreated and previously treated patients with gastric carcinoma. In a multinational phase II trial (TAX 325), 158 untreated patients with advanced gastric cancer (99% without prior chemotherapy) were randomized to receive, every 3 weeks, either docetaxel 85?mg/m2 plus cisplatin 75?mg/m2 (TC) or docetaxel 75?mg/m2 plus cisplatin 75?mg/m2, plus a 5-day continuous infusion of 750?mg/m2 5-fluorouracil (FU; TCF). By intent-to-treat analysis, patients receiving TCF had a significantly higher response rate and longer time to progression. Overall survival in the two arms was not significantly different. Toxicity (particularly gastrointestinal toxicity) was greater with the TCF combination than in the TC arm, and there was a greater need for dose reduction. However, adverse events in both arms were manageable and there were no deaths associated with either regimen. Following these findings, a phase III trial comparing a control arm of cisplatin plus 5-FU against an experimental arm consisting of the TAX 325 phase II docetaxel/cisplatin/5-FU regimen is now in progress. 相似文献
5.
Purpose
To determine the maximum-tolerated dose (MTD) of a 24-h continuous infusion of 5-fluorouracil (5-FU) when administered in combination with a fixed weekly dose of docetaxel and cisplatin in patients with advanced gastric cancer.Methods
Patients with advanced gastric adenocarcinoma (n = 21) received a weekly regimen of docetaxel, cisplatin and 5-FU (DCF) for 3 consecutive weeks every 4 weeks. The doses of docetaxel and cisplatin were fixed at 33.3 and 30 mg/m2, respectively. The dose of 5-FU was increased from a starting dose of 1,000 mg/m2 to the MTD.Results
A total of 53 cycles of chemotherapy were administered (median = 3 cycles/patient). The MTD of 5-FU was 1,750 mg/m2. All 21 patients were assessed for toxicity and 19 patients (90%) were evaluated for response. Both grade 3–4 hematologic and non-hematologic toxicities occurred in less than 10% of patients and there were no treatment-related deaths. Among the 19 patients, we observed 1 complete and 4 partial responses for an overall response rate of 26% (95% CI: 6–46%). This rate increased to 39% (95% CI: 12–66%) in 13 chemotherapy-naïve patients.Conclusions
A consecutive weekly DCF regimen at 4-week intervals appears feasible for advanced gastric cancer with a favorable toxicity profile. The recommended doses are 33.3 mg/m2 of docetaxel, 30 mg/m2 of cisplatin and 1,500 mg/m2 of a 24-h continuous intravenous infusion of 5-FU. The response of this weekly regimen in our study was favorable and deserved further investigation in a phase II trial. 相似文献6.
Paal Fr Brunsvig Anders Andersen Steinar Aamdal Vessela Kristensen Harald Olsen 《BMC cancer》2007,7(1):197
Background
Previous pharmacokinetic studies with docetaxel have mostly used 3-weekly (75 mg/m2 and 100 mg/m2) or weekly regimens (35–40 mg/m2). The pharmacokinetics and radiosensitizing efficacy of weekly 20 mg/m2 docetaxel, has however not been well characterized. We examined the pharmacokinetics of weekly docetaxel when administered with concurrent radiotherapy and compared the results with a 3-weekly 100 mg/m2 regimen. 相似文献7.
J. F. Cleary Rhoda Arzoomanian Donna Alberti Chris Feierabend Barry Storer Pauline Witt P. P. Carbone George Wilding 《Cancer chemotherapy and pharmacology》1997,39(4):300-306
Purpose: The activity of 5-fluorouracil (5-FU) against colon cancer is enhanced by leucovorin and the combination of 5-FU and levamisole
has activity in the adjuvant treatment of colonic malignancies. The combination of 5-FU with both leucovorin and levamisole
may provide additional benefit in the treatment of colon cancer. Methods: A phase I study to assess qualitative and quantitative toxicities of this three-drug combination and to determine a dose
for further phase II testing was undertaken. The role of levamisole as an immunomodulator was also assessed. Results: A group of 38 patients with incurable etastatic malignancies received 119 cycles of treatment at eight dose levels. 5-FU
(375 mg/m2 per day) and leucovorin (200 mg/m2 per day) were administered intravenously (days 1–5). Levamisole was administered orally (days 1–3 and 15–17) at doses from
30 to 470 mg/m2 per day. Patients received both 5FU/leucovorin and 5-FU/leucovorin/levamisole in random order for their initial two cycles.
All subsequent treatments were with the three-drug combination. Toxicities included nausea, vomiting, stomatitis, thrombocytopenia
and granulocytopenia. Diarrhea was the dose-limiting toxicity at 470 mg/m2 per day levamisole. The addition of levamisole resulted in more toxicity than 5-FU and leucovorin alone. No clinical responses
were seen with this regimen. The addition of levamisole resulted in more immunomodulation than 5-FU and leucovorin alone as
evidenced by release of neopterin from monocytes. Conclusion: With this schedule and dose of 5-FU and leucovorin, the maximum tolerated dose of levamisole was 354 mg/m2. However, given the lack of response and the absence of dose-dependent immunomodulation, this may not be the appropriate
dose for further phase 11 studies.
Received: 20 October 1995 / Accepted: 16 June 1996 相似文献
8.
《Annals of oncology》2014,25(7):1373-1378
BackgroundSome trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer.Patients and methodsPatients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m2 day 1, LV 100 mg/m2 as 2 h infusion and 5-FU 400 mg/m2 as bolus, days 1 and 2 followed by 600 mg/m2/day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm).ResultsFrom February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85–1.17; P = 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82–1.18; P = 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively.ConclusionsA more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy.Clinical trial registrationClinicalTrials.gov Identifier: NCT01640782. 相似文献
9.
F. Caponigro P. Comella F. Rivellini A. Avallone A. Budillon E. Di Gennaro N. Mozzillo F. Ionna V. De Rosa L. Manzione G. Comella 《Annals of oncology》2000,11(5):575-580
Background:The combination of cisplatin (CDDP) and 5-fluorouracil(5-FU) can be regarded as a reference regimen in squamous cell carcinoma ofthe head and neck (SCCHN). Raltitrexed (Tomudex) is a direct and specificthymidilate synthase (TS) inhibitor, which has shown clinical activity againstSCCHN in a previous phase I study, when combined with 5-FU and levo-folinicacid (LFA). Preclinical data support the combination of CDDP and raltitrexed.The aim of the present study was to evaluate the combination of cisplatin,raltitrexed, LFA and 5-FU in a phase I–II study.
Patients and methods:Patients with locally advanced or metastaticSCCHN were treated with a combination of cisplatin at the starting dose of 40mg/m2, followed by raltitrexed at the starting dose of 2.5mg/m2 on day 1; levo-folinic acid at fixed dose of 250mg/m2, followed by 5-fluorouracil at the starting dose of 750mg/m2 on day 2. Doses of the three cytotoxic agents werealternately escalated up to dose-limiting toxicity (DLT). Treatment wasrecycled every two weeks and given up to a maximum of eight courses; afterchemotherapy, patients with locally advanced disease received a locoregionaltreatment.
Results:Forty-five patients were entered into the study. Six doselevels were tested. At CDDP 50 mg/m2, raltitrexed 3mg/m2, 5-FU 900 mg/m2, four out of six patients showedDLT, which was in all cases grade 4 neutropenia. Therefore, this dose levelwas defined as maximum tolerated dose (MTD). CDDP 60 mg/m2,raltitrexed 2.5 mg/m2, LFA 250 mg/m2, 5-FU 900mg/m2 was the dose level recommended for phase II. CDDP,Raltitrexed and 5-FU mean actually delivered dose intensities at the selecteddose level were 26, 1.05, and 378 mg/m2/week, respectively.Neutropenia was the main side effect and was observed even at the lowest doselevels. Non-hematologic side effects were mild. Nine complete responses(20%) and twenty-one partial responses (47%) were observed, foran overall response rate of 67% (95% confidence interval(95% CI): 51%–80%), according to intention to treatanalysis. Fifteen of fifteen patients (100%) treated at the dose levelselected for phase II had an objective response (5 complete responses, 10partial responses).
Conclusions:The results of our dose escalation clearlydemonstrate that it is possible to combine CDDP, raltitrexed, and modulated5-FU at effective doses, without unexpected toxicities. The response datapoint to an impressive clinical activity, which will be better defined by anongoing large phase II study. 相似文献
10.
Paolo Piacentini Emilia Durante Annarita Trolese Anna Mercanti Andrea Bonetti 《Gastric cancer》2012,15(1):106-110
Abstract
The combination of Taxotere (docetaxel), cisplatin, and prolonged-infusion 5-fluorouracil (5-FU) has emerged as an active treatment for advanced gastric cancer. However, the regimen proposed by van Cutsem et al. (J Clin Oncol 24:4991–7, 2006) is associated with significant toxicity and therefore alternative schedules are needed. In the present study, patients with advanced gastric or esophageal cancer received Taxotere 35 mg/m2 and cisplatin 25 mg/m2 on day 1, followed by 5-FU 180 mg/m2/day as a 7-day prolonged infusion. Drugs were given weekly for 3 consecutive weeks followed by 1 week’s rest. Cycles were repeated every 4 weeks. Overall, a total of 110 cycles were administered to 27 patients (median age 63 years, range 40–78 years). The median number of cycles per patient was 4 (range 2–6). Nine partial responses were obtained, resulting in an overall response rate of 33% [95% confidence interval (CI) 16–51], a median time to progression of 6.4 months (95% CI 5.4–7.4), and a median overall survival of 10.7 months (95% CI 6.6–14.8). Toxicity was mild; grade III-IV neutropenia was the most frequently observed side effect, in 9 administered cycles (8%); neutropenia was complicated by fever in 2 cycles. Other grade III–IV toxicities observed in >5% of patients were anemia and mucositis. 相似文献11.
Park KW Ahn JS Park YS Lee J Kang JH Park JO Lim HY Im YH Kang WK Park K Lee SI 《Cancer chemotherapy and pharmacology》2007,59(1):17-21
Purpose: Docetaxel, as a single agent, has demonstrated activity in patients with advanced gastric cancer and cisplatin has shown lack of overlapping toxicities with docetaxel. Therefore, we conducted a phase II study to assess the efficacy and the toxicity of a combination regimen of docetaxel plus cisplatin in patients with advanced gastric cancer who have never been treated with palliative chemotherapy. Methods: Ninety-two patients with metastatic gastric cancer were enrolled from April 2000 to March 2004. Patients with histologically confirmed gastric adenocarcinoma, at least one bi-dimensionally measurable lesion, no prior palliative chemotherapy and at least 6 months from the end of adjuvant chemotherapy were eligible for study entry. Docetaxel 75 mg/m2 and cisplatin 75 mg/m2 were given on day 1. The cycle was repeated every 3 weeks. The objective response was evaluated after three cycles of chemotherapy. Toxicity was assessed according to the National Cancer Institute common toxicity criteria scale version 2.0. Results: In total, 401 cycles were administered, with a median of 5 cycles per patient (range 1–9 cycles). The median age was 56 years (range 31–76). Eighty-six patients were evaluable for treatment response. The objective response rate was 43.5% (95% CI, 33.4–53.6) with one complete response and 39 partial responses. Twenty patients (21.7%) had stable disease and 26 patients (28.3%) had a progression. The median time to progression was 7.0 months (95% CI, 5.0–9.0) and the median overall survival was 11.5 months (95% CI, 9.5–13.4). The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia (17.4%), nausea/vomiting (13.0%) and diarrhea (7.6%). Conclusion: The combination chemotherapy of docetaxel with cisplatin in advanced gastric cancer was tolerable for most patients and showed a promising antitumor activity as a first-line therapy.Keon Woo Park and Jin Seok Ahn contributed equally to this work. 相似文献
12.
Andrade J. M. Carrara H. H. A. Pimentel F. F. Marana H. R. C. Macchetti A. H. Mouro L. R. Zola F. E. Tiezzi D. G. 《Medical oncology (Northwood, London, England)》2010,27(1):65-72
The feasibility, safety, and efficacy of planned sequential administration of docetaxel and irinotecan with 5-fluorouracil
(5-FU)/leucovorin in advanced upper gastrointestinal adenocarcinoma (UGIA) are unknown. Seventy-three patients with gastric
(GC; n = 22), pancreatic (PC; n = 28) or biliary cancer (BC; n = 23) were randomised to start with 45 mg/m2 docetaxel or 180 mg/m2 irinotecan combined with 5-FU/leucovorin every 2nd week. After every 2nd course, the patients were crossed over to the other
combination. Treatment was given for a maximum of 12 courses. Quality-of-life (QoL) was evaluated during the first two months
using the EORTC QLQ-C30. Eighteen patients (25%; GC 32%, PC 21%, BC 22%) demonstrated partial response (PR) and 21 (29%) had
prolonged stable disease. Mean QoL scores were low at baseline. Twenty-three (32%) patients had improved QoL using a summary
measure and 13 were stable. Median time to progression was 4.4 months and overall survival 8.2 months. The treatments were
reasonably well tolerated. Grade 3–4 toxicities were slightly more common for the docetaxel combination. There were two treatment-related
deaths. Planned sequential treatment with docetaxel or irinotecan with 5-FU/leucovorin is feasible, reasonably tolerable and
appears active in advanced UGIA. 相似文献
13.
Françoise Bressolle Jean M. Joulia Frédéric Pinguet Marc Ychou Cécile Astre Jacqueline Duffour Roberto Gomeni 《Cancer chemotherapy and pharmacology》1999,44(4):295-302
Purpose: The purpose of this work was to estimate the population pharmacokinetic parameters of 5-fluorouracil (5-FU) in patients
with advanced colorectal cancer using circadian change kinetics. Methods: Eighty-five patients (32 females, 53 males) were enrolled onto this study. All patients received folinic acid (200 mg/m2) by intravenous infusion over 2 h followed by a 5-FU loading dose (400 mg/m2) and then continuous infusion (600 mg/m2) for 22 h. This whole regimen was repeated on day 2 and was given on a 14-day cycle. Plasma 5-FU determinations were performed
by high-performance liquid chromatography with ultraviolet absorbance detection. Pharmacokinetic analyses were performed using
the NONMEM computer program through the Visual-NM graphical interface. An open one-compartment pharmacokinetic model with
zero-order input rate was used to describe the kinetics of 5-FU; moreover, circadian time-dependent changes in 5-FU concentrations
were taken into account in the model. The circadian model was defined as the sum of two cyclic components; the amplitude of
the first cyclic component (over 24 h) was about 30% of the average clearance and the amplitude of the second cyclic component
(over 12 h) was about 50% of the amplitude of the first component. The acrophase (peak) times of the first and the second
periodic component were 04 h 12 m and 00 h 25 m, respectively. The potential sources of variability on the population parameters
(65 patients) were investigated using patient's sex, body area, age, body weight, height, liver enzymes and serum creatinine
as covariables. Results: Only the estimated clearance circadian changes were different for the two sexes. The population parameter estimates of mean
clearance (CL
mean
) and initial volume of distribution (V), were as follows: the male subgroup showed a CL
mean
value twice larger (125 l/h) than the value observed in the female subgroup (65 l/h), and V = 21 l. A validation group of
20 additional patients was used to evaluate the predictive performances of the population parameters. The individual pharmacokinetic
parameters were computed by means of a Bayesian fitting procedure. From the resulting individualized parameter values, concentrations
of 5-FU in the plasma were calculated. To evaluate the performance of the Bayesian estimation, the experimental concentrations
were compared with the predicted ones. Conclusion: In conclusion, a chronomodulated delivery schedule of 5-FU should be performed, using a perfusion rate inversely proportional
to the circadian variations of clearance in order to maintain stable 5-FU plasma levels. Such a treatment schedule may result
in increased effectiveness of the treatment and decreased occurrence of drug-associated side-effects. The present study develops
a complete procedure to efficiently estimate 5-FU clearance in order to optimize dosage regimens in individual patients.
Received: 21 September 1998 / Accepted: 20 January 1999 相似文献
14.
Arnaud D. Roth 《Gastric cancer》2002,5(1):27-29
The combination of docetaxel with cisplatin in gastric cancer is a promising development. In a phase II study, 85–100?mg/m2 docetaxel plus 75?mg/m2 cisplatin was established as an active regimen in advanced gastric cancer (with an overall response rate of 56%) with a manageable safety profile. Up to 300?mg/m2 5-fluorouracil (5-FU) given by continuous infusion for 2 of 3 weeks can be added to this regimen without an increase in appreciable toxicity. The efficacy of docetaxel-based regimens remains to be established by a randomized phase III study. However, the results of such trials are eagerly awaited, as are data from studies of docetaxel-based combinations in the adjuvant and neoadjuvant settings. 相似文献
15.
Joel M. Reid John S. Kovach Michael J. O'Connell Pamela G. Bagniewski Charles G. Moertel 《Cancer chemotherapy and pharmacology》1998,41(6):477-484
Purpose: To determine the maximum tolerable dose (MTD) and activity of levamisole administered concurrently with 5-fluorouracil (5-FU)
in a standard 5-day course. To determine the pharmacokinetics of levamisole during the course of treatment. Patients and methods: Levamisole was administered to 38 patients orally three times a day for 5 days concurrently with a course of 5-FU administered
daily by rapid intravenous injection for 5 days. Toxicity was evaluated in 20 patients who received escalating doses of levamisole.
The activity of the combination was evaluated in 18 patients who received levamisole at the MTD with 5-FU. The pharmacokinetics
of levamisole were characterized in ten patients at the MTD level. Results: Intractable vomiting, confusion and vertigo were the major dose-limiting toxicities. The MTD of oral levamisole was 100 mg/m2 administered three times a day concurrently with 450 mg/m2 per day intravenous 5-FU for 5 consecutive days. Partial responses lasting 5 and 11 months were observed in 2/18 patients
with measurable disease at the MTD. Peak plasma concentrations of 1 μg/ml (range 0.6–1.3 μg/ml) were achieved 90 min (range
60–360 min) after an oral dose of 100 mg/m2 levamisole with a 3.5-fold accumulation noted following 4 days of administration. Peak plasma concentrations of p-hydroxylevamisole were about 5% of parent drug. Little parent drug (2–5%) was detected in urine. Conclusions: Levamisole may be administered safely with 5-FU at doses which are up to four to five times greater than those presently
given in conventional regimens. The recommended dose of levamisole combined with 5-FU for future research protocols is 75 mg/m2 t.i.d for 5 days.
Received: 31 December 1996 / Accepted: 11 September 1997 相似文献
16.
Objective We assessed the safety and efficacy of two regimens for patients with gastrointestinal cancers: continuous-infusion (Cl) schedules
of 5-Fluorouracil (5-Fu) plus a platinum (cisplatin or oxaliplatin) with/or without paclitaxel (regimen A) versus Xeloda plus
a platinum (cisplatin or oxaliplatin) with/or without paclitaxel for oral use (regimen B) in patients with gastrointestinal
cancers.
Methods Between May 2003 and May 2005, 84 patients diagnosed in Jiangsu Cancer Hospital & Research Institute with locally advanced
esophageal, gastric or colorectal cancer were registered. Regimen A and B consisted of either 5-Fu 0.375 Cl days 1–14, every
28 days (n = 44), or Xeloda 1000 mg twice daily, days 1–14, every 28 days (n = 40). For both regimen A and B, IV cisplatin 25 mg/m2 was administered on day 1, 2 and 3 (or Oxaliplatin 75mg/m2 on day 1, 8 and 15) with or without paclitaxel 60–75 mg/m2 on day1, 8 and 15.
Results Patients receiving regimen B experienced significantly less stomatitis (P < 0.05) and diarrhea (P < 0.05), than those receiving regimen A. Prevalence of nausea/vomiting, alopecia, neutropenia, and hand-foot syndrome without
significant difference between two regimens. No treatment related death occurred during study period. Regimen B demonstrates
a similar, favorable safety profile in this study. Response rates and rates of clinical benefit for regimen A and B were 40.9%,
40.0% and 43.2%, 65.0% respectively.
Conclusion Based on its improved safety profile and improved rate of clinical benefit, Xeloda has the potential to replace Cl 5-FU as
an alternative treatment for patients with gastrointestinal cancers.
Supported by grants from the Jiangsu Provincial Personnel Department “the Great of Six Talented Man Peak” Project and the
Jiangsu Cancer Hospital Emphasis Project (No. ZK200602). 相似文献
17.
Liqing Li Liangxi Pan Mingzhong Li Fengzhan Qin Lingyuan Zeng 《中德临床肿瘤学杂志》2008,7(3):135-137
Objective: To evaluate the efficacy and safety of Oxaliplatin in the patients with colorectal cancer. Methods: In a multicenter randomized control study, a total of 144 patients were divided into four groups: Oxaliplatin (Haitong) + 5-FU, CF (group A) 41 cases; 5-FU + CF (group B) 41 cases; Oxaliplatin (Haitong) + 5-FU, CF (group C) 31 cases; Oxaliplatin (positive drug) + 5-FU + CF (group D) 31 cases. Oxaliplatin combination regimen: L-OHP 130 mg/m2 i.v. infusion 2 h dl; CF 200 mg/m2 i.v. 2 h d1-d5; 5-FU 300 mg/m2 i.v. infusion 4 h d1-d5 (after CF). 5-FU + CF combination regimen: CF 200 mg/m^2 i.v. infusion 2 h d1-d5, 5-FU 300 mg/m^2 i.v. infusion 4h d1-d5 (after CF), the schedule was repeated every 3 weeks. The total cycles were 3. Results: After three circles treatment, overall response rate of 4 groups was 24.4% (group A), 2.4% (group B), 25.8% (group C) and 19.4% (group D), respectively. The response rate was significantly different between group A and group B (P 〈 0.01), but no significant difference was observed between group C and group D (P 〉 0.05). Conclusion: The Oxaliplatin (Haitong) for injection combination regimen is effective in the treatment of celorectal cancer. 相似文献
18.
Tanaka Y Yoshida K Sanada Y Osada S Yamaguchi K Takahashi T 《Cancer chemotherapy and pharmacology》2010,66(6):1159-1165
Background and purpose
The optimal chemotherapeutic protocol for the treatment of esophageal cancer has not yet been established. A dose-escalation study of docetaxel combined with cisplatin and 5-fluorouracil (5-FU) was performed to determine the optimal dose in patients with advanced esophageal squamous cell carcinoma.Patients and method
We studied a total of 18 patients who had previously untreated thoracic esophageal squamous cell carcinoma with T4 tumors and/or metastasis. The patients received an infusion of docetaxel at different dose levels (levels 1, 2, 3: 30, 35, 40 mg/m2, respectively) and an infusion of cisplatin (40 mg/m2) on days 1 and 15 plus a continuous infusion of 5-FU (400 mg/m2/day) on days 1–5 and 15–19.Results
Dose-limiting toxicities (DLT) included febrile neutropenia and leukopenia. DLT occurred in 2 of 6 patients at level 1, 2 and in 3 of 6 patients at level 3. The response rate was 88.9%, including a complete response rate of 33.3%.Conclusions
To minimize toxicity and maximize dose intensity, we elected to investigate a biweekly regimen. The maximum tolerated dose was level 3, and the recommended dose was determined to be docetaxel 35 mg/m2 with cisplatin 40 mg/m2 plus 5-FU 400 mg/m2, administered biweekly. This regimen was tolerable and highly active. A phase II study has been started. 相似文献19.
S. P. Khor H. Amyx Stephen T. Davis Donald Nelson David P. Baccanari Thomas Spector 《Cancer chemotherapy and pharmacology》1996,39(3):233-238
The pharmacokinetics of 5-fluorouracil (5-FU) in different animal species treated with the dihy-dropyrimidine dehydrogenase
(DPD) inactivator, 5-ethynyluracil (776C85) were related through allometric scaling. Estimates of 5-FU dose in combination
with 776C85 were determined from pharmacokinetic and toxicodynamic analysis. Method: The pharmacokinetics of 5-FU in the DPD-deficient state were obtained from mice, rats and dogs treated with 776C85 followed
by 5-FU. The pharmacokinetics of 5-FU in humans were then estimated using interspecies allometric scaling. Data related to
the clinical toxicity for 5-FU were obtained from the literature. The predicted pharmacokinetics of 5-FU and the clinical
toxicity data were then used to estimate the appropriate dose of 5-FU in combination with 776C85 in clinical trials. Results: The allometric equation relating total body clearance (CL) of 5-FU to the body weight (B) (CL=0.47B0.74) indicates that clearance increased disproportionately with body weight. In contrast, the apparent volume of distribution
(Vc) increased proportionately with body weight (Vc=0.58 B0.99). Based on allometric analysis, the estimated clearance of 5-FU (10.9 l/h) in humans with DPD deficiency was comparable to
the observed values in humans lacking DPD activity due to genetic predisposition (10.1 l/h), or treatment with 776C85 (7.0 l/h)
or (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVdUrd, 6.6 l/h). The maximum tolerated dose (MTD) of 5-FU in combination with 776C85
was predicted from literature data relating toxicity and plasma 5-FU area under the concentration-time curve (AUC). Based
on allometric analysis, the estimated values for the MTD in humans treated with 776C85 and receiving 5-FU as a single i.v.
bolus dose, and 5-day and 12-day continuous infusions were about 110, 50 and 30 mg/m2 of 5-FU, respectively. Discussion: The pharmacokinetics of 5-FU in the DPD-deficient state in humans can be predicted from animal data. A much smaller dose
of 5-FU is needed in patients treated with 776C85.
Received: 6 October 1995/Accepted: 28 May 1996 相似文献
20.
Purpose Radiotherapy (RTx) has been considered as the treatment for locally advanced squamous cell carcinoma of the head and neck
(SCCHN). However, with only conventional fractionation (Cfx), response rates are relatively low. In this study, we report
the results of hyperfractionation (Hfx) RTx with concurrent docetaxel, cisplatin and 5-fluorouracil (TPF) chemotherapy (CTx)
in patients with locally advanced SCCHN and compare Hfx and Cfx RTx with concurrent TPF CTx.
Methods Fifty patients with previously untreated stage III–IV SCCHN were entered into this study. Eligible patients received RTx delivered
using arm 1: Hfx at 1.2 Gy/fraction, twice daily, 5 days/week to 76.8 Gy/64 fractions, and arm 2: Cfx at 2 Gy/fraction/day,
5 days/week to 70 Gy/35 fractions. Patients received 2 cycles CTx every 4 weeks. The doses were docetaxel 50 mg/m2 (day 1), cisplatin 60 mg/m2 (day 4), and 5-FU 600 mg/m2/day (days 1–5).
Results The overall clinical response rate and the pathological CR were 100% (25/25) and 84% (21/25) in arm 1, and 100% (25/25) and
80% (20/25) in arm 2. Local–regional control was better significant in arm 1 than arm 2 (P = 0.048). There were also trend toward improved disease-free survival (P = 0.059) and overall survival (P = 0.078) in arm 1. Mucositis was significantly more frequent in arm 1 (P = 0.048).
Conclusion There were trend toward improved local–regional control, disease-free survival and overall survival in Hfx RTx with concurrent
TPF CTx, compared to Cfx RTx with concurrent TPF CTx. 相似文献