Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new efudex research articles will be listed here shortly after becoming available to us.
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Medical research on efudex
Cancer Chemother Pharmacol. 2008 Oct 7;
Fornaro L, Masi G, Bursi S, Loupakis F, Vasile E, Antonuzzo A, Chiara S, Pfanner E, Di Paolo A, Bocci G, Del Tacca M, Falcone A
PURPOSE: The GONO-FOLFOXIRI regimen demonstrated higher activity and efficacy than FOLFIRI in metastatic colorectal cancer patients. The aim of this study was to determine the maximum tolerated dose of capecitabine, in substitution of 5-fluorouracil, combined with oxaliplatin and irinotecan and to evaluate the pharmacokinetics of the drugs. PATIENTS AND METHODS: We treated 15 patients with escalating doses of capecitabine (from day 1 to 7) and fixed doses of oxaliplatin (85 mg/m(2)) plus irinotecan (165 mg/m(2)) (both administered on day 1), repeated every 2 weeks. Pharmacokinetic analysis was performed on plasma samples collected at the first cycle of treatment. RESULTS: The maximum tolerated dose of capecitabine resulted 2,000 mg/m(2)/day, with diarrhea being the only dose-limiting toxicity. Large interpatient variability in the pharmacokinetic parameters of investigated drugs was observed. Results in terms of activity are promising. CONCLUSIONS: At the maximum tolerated dose of capecitabine of 2,000 mg/m(2)/day the combination is feasible with promising activity and deserves further investigations.
Chemotherapy for Colorectal Cancer Liver Metastases.
Oncologist. 2008 Oct 6;
Alberts SR, Wagman LD
Colorectal cancer (CRC) is a highly prevalent malignant disease in industrialized nations. The annual incidence of invasive CRC in the U.S. is among the highest in the world, and the liver is the only metastatic site in approximately one third of patients. Without treatment, patients with metastatic disease have a poor prognosis; however, long-term survival benefits and even cure have been reported in patients undergoing surgical resection of metastases. In addition, advances in chemotherapy, imaging, and surgical techniques have increased the proportion of patients who are eligible for resection. Combination therapy with fluorouracil and leucovorin has been the mainstay of treatment for metastatic CRC; however, the introduction of newer agents, such as oxaliplatin and irinotecan, and targeted agents, such as cetuximab and bevacizumab, has yielded improvements in response rates (RRs) and survival. Maximizing the exposure of hepatic metastases to high target concentrations of cytotoxic drugs using hepatic arterial infusion (HAI) increases RRs further than with systemic chemotherapy; however, the impact of HAI on survival is unclear. As the goals of chemotherapeutic treatment for metastatic CRC increasingly shift from palliation to prolongation of survival, improvement in RRs, and downsizing of tumors in order to enable or optimize resection, treatment in a multidisciplinary environment involving a medical oncologist, radiologist, and surgical oncologist with hepatobiliary expertise will become central to deciding the best course of therapy and timing of surgery.
Breast cancer resistance protein expression and 5-fluorouracil resistance.
Biomed Environ Sci. 2008 Aug; 21(4): 290-5
Yuan JH, Cheng JQ, Jiang LY, Ji WD, Guo LF, Liu JJ, Xu XY, He JS, Wang XM, Zhuang ZX
OBJECTIVE: To filtrate breast cancer resistance protein (BCRP)-mediated resistant agents and to investigate clinical relationship between BCRP expression and drug resistance. METHODS: MTT assay was performed to filtrate BCRP-mediated resistant agents with BCRP expression cell model and to detect chemosensitivity of breast cancer tissue specimens to these agents. A high performance liquid chromatography (HPLC) assay was established, and was used to measure the relative dose of intracellular retention resistant agents. RT-PCR and immunohistochemistry (IHC) were employed to investigate the BCRP expression in breast cancer tissue specimens. RESULTS: MTT assay showed that the expression of BCRP increased with the increasing resistance of 5-fluorouracil (5-Fu) (P
Med Princ Pract. 2008; 17(6): 496-9
Chen CW, Wang WM, Su YC, Wu JY, Hsieh JS, Wang JY
OBJECTIVE: To present our clinical experience of 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen administered as an adjuvant chemotherapy to 2 patients with advanced jejunal adenocarcinoma. CASE PRESENTATION AND INTERVENTION: A 55-year-old woman presented with recurrent upper abdominal pain, nausea and vomiting. A small bowel series as well as the abdominal computed tomography scan revealed an irregular narrowing lesion at the proximal jejunum. The patient then underwent an exploratory laparotomy and the jejunal adenocarcinoma with localized peritoneal metastasis was found (R0 resection, T3N1M1, stage IV). Chemotherapy with FOLFOX4 regimen of 12 cycles was initiated after the curative resection. No adverse event was observed during the period of chemotherapy. She has been well without evidence of recurrence for over 20 months postoperatively. The second case was a 77-year-old female presenting with mechanical ileus. Surgical exploration revealed a proximal jejunal adenocarcinoma with regional lymph node involvement (R0 resection, T3N1M0, stage III). She also received the FOLFOX4 chemotherapy of 12 cycles with an uneventful course. No obvious toxicity developed except for temporary grade I peripheral neuropathy and skin eruption. This patient has survived well and has been free of this disease for over 12 months since the operation. CONCLUSION: This report showed that adjuvant chemotherapy with FOLFOX4 regimen seems effective and well tolerated in these 2 patients with advanced jejunal adenocarcinoma. Further investigation of a large number of patients with long-term follow-up is needed to confirm these findings.
Ann Oncol. 2008 Oct 3;
Bollschweiler E, Metzger R, Drebber U, Baldus S, Vallböhmer D, Kocher M, Hölscher AH
BACKGROUND: This study investigates response and prognosis after neo-adjuvant chemoradiation (CTx/RTx) in patients with advanced esophageal carcinoma, according to histological type. PATIENTS AND METHODS: Patients with uT3 carcinoma of the esophagus treated with curative-intention esophagectomy from 1997 until 2006 were included in this retrospective analysis. Patients receiving preoperative CTx/RTx (5-fluorouracil, cisplatin, 36 Gy) were compared with those with primary surgery for pT3 tumors. Therapy response after CTx/RTx was evaluated using 'Cologne Regression Grade' (minor response: >/=10% vital residual tumor cells (VRTCs), major response:
Targeting colon cancer cells using PEGylated liposomes modified with a fibronectin-mimetic peptide.
Int J Pharm. 2008 Sep 19;
Garg A, Tisdale AW, Haidari E, Kokkoli E
Integrin alpha(5)beta(1) is expressed on several types of cancer cells, including colon cancer, and plays an important role in tumor growth and metastasis. The ability to target the integrin alpha(5)beta(1) using an appropriate drug delivery nano-vector can significantly help in inhibiting tumor growth, reducing tumor metastasis, and decreasing deleterious side effects associated with different cancer therapies. Liposomes are nano-sized phospholipid bilayer vesicles that have been extensively studied as drug delivery carriers. The goal of this study is to design stealth liposomes (liposomes covered with polyethylene glycol (PEG)) that will target colon cancer cells that express the integrin alpha(5)beta(1). The PEG provides a steric barrier allowing the liposomes to circulate in the blood and the functionalizing moiety, PR_b peptide, will specifically recognize and bind to alpha(5)beta(1) expressing cells. PR_b is a novel peptide sequence that mimics the cell adhesion domain of fibronectin, and includes four building blocks, RGDSP (the primary recognition site for alpha(5)beta(1)), PHSRN (the synergy site for alpha(5)beta(1)), a (SG)(5) linker, and a KSS spacer. In this study we have demonstrated that by varying the amount of PEG (PEG750 or PEG2000) and PR_b on the liposomal interface we can engineer nano-vectors that bind to CT26.WT, HCT116, and RKO colon cancer cells in a specific manner and are internalized through most likely alpha(5)beta(1)-mediated endocytosis. GRGDSP-targeted stealth liposomes bind to colon cancer cells and internalize, but they have much lesser efficiency than PR_b-targeted stealth liposomes, and more importantly they are not as specific since many integrins bind to RGD peptides. PR_b-targeted stealth liposomes are as cytotoxic as free 5-Fluorouracil (5-FU) and exert the highest cytotoxicity on CT26.WT cells compared to GRGDSP-targeted stealth liposomes and non-targeted stealth liposomes. Thus, the proposed targeted delivery system has the great potential to deliver a therapeutic load directly to colon cancer cells, in an efficient and specific manner.
A novel electrophysiological model of chemotherapy-induced cognitive impairments in mice.
Neuroscience. 2008 Sep 9;
Gandal MJ, Ehrlichman RS, Rudnick ND, Siegel SJ
Purpose: Chemotherapeutic agents are known to produce persistent cognitive deficits in cancer patients. However, little progress has been made in developing animal models to explore underlying mechanisms and potential therapeutic interventions. We report an electrophysiological model of chemotherapy-induced cognitive deficits using a sensory gating paradigm, to correspond with performance in two behavioral tasks. EXPERIMENTAL DESIGN: Mice received four weekly injections of methotrexate and 5-fluorouracil. Whole-brain event-related potentials (ERPs) were recorded throughout using a paired-click paradigm. Mice underwent contextual fear conditioning (CFC) and novel-object recognition testing (NOR). RESULTS: Chemotherapy-treated animals showed significantly impaired gating 5 weeks after drug treatments began, as measured by the ratio of the first positive peak in the event-related potential (P1)-first negative peak in the event-related potential (N1) between first and second auditory stimuli. There was no effect of drug on the amplitude of P1-N1 or latency of P1. The drug-treated animals also showed significantly increased freezing during fear conditioning and increased exploration without memory impairment during novel object recognition. CONCLUSIONS: Chemotherapy causes decreased ability to gate incoming auditory stimuli, which may underlie associated cognitive impairments. These gating deficits were associated with a hyperactive response to fear conditioning and reduced adaptation to novel objects, suggesting an additional component of emotional dysregulation. However, amplitudes and latencies of ERP components were unaffected, as was NOR performance, highlighting the subtle nature of these deficits.
Basic Clin Pharmacol Toxicol. 2008 Oct; 103(4): 305-13
Kang SJ, Lee YJ, Kim BM, Kim YJ, Woo HD, Jeon HK, Chung HW
Despite the excellent chemotherapeutic effect of 5-fluorouracil, its cytotoxicity and genotoxicity in normal cells remain a major problem. We sought to assess whether Bupleuri Radix extract enhances 5-fluorouracil-induced cytotoxicity in HepG2 hepatoma cells, while protecting normal blood lymphocytes. Bupleuri Radix, used for treatment of liver disease in oriental medicine, possesses antitumour properties; it induces apoptosis through cell arrest in tumour cells, but does not affect normal lymphocytes. In this study, we evaluated the protective and enhancing effects of Bupleuri Radix on 5-fluorouracil-induced cytotoxicity in HepG2 cells and normal lymphocytes. Treatment with Bupleuri Radix increased the micronuclei frequency and DNA damage, resulting from 5-fluorouracil treatment. However, when human lymphocytes were cotreated with Bupleuri Radix and 5-fluorouracil, the frequency of 5-fluorouracil-induced micronuclei decreased. Although the extent of 5-fluorouracil-induced DNA damage, determined by single-cell gel electrophoresis, increased after treating HepG2 cells with Bupleuri Radix, it decreased in normal lymphocytes. When cells were treated with 20 microM 5-fluorouracil and 200 microg/ml Bupleuri Radix simultaneously, Bax protein increased in HepG2 cells at 24 hr; however, p21 and p53 proteins were up-regulated in normal human lymphocytes. Cotreatment with 200 microg/ml Bupleuri Radix and 20 microM 5-fluorouracil resulted in cell arrest at the late G(1)/early S phase in HepG2 cells (55.80 +/- 0.19%) and normal lymphocytes (97.19 +/- 0.27%). In addition, Bupleuri Radix and 5-fluorouracil treatment increased mitochondria membrane potential collapse only in HepG2 cells (19.02%), while it was not changed in lymphocytes. In conclusion, our findings suggest that Bupleuri Radix may be effective as a therapeutic agent to treat hepatomas.
[The combined treatment of colorectal cancer with liver metastases]
Khirurgiia (Mosk). 2008; 20-3
The direct and follow-up results of surgical and combined treatment of colorectal cancer with liver metastases are presented. Complication rate after liver resections was 28.4% and lethality was 3.5%. Follow-up results evidence the decrease of survival in patients with adjuvant chemotherapy after surgery. The safety of oxalyplatin in patients after liver resections, including its intraarterial infusion through the hepatic artery is shown. Oxalyplatin-based chemotherapy regimen tended to be more effective in comparison with 5-fluorouracil scheme, especially in patients with synchronous or multiple liver metastases. Considering that the difference is not statistically significant, further studies of oxalyplatin influence on survival of patients with colorectal liver metastases are necessary.
Effects of Human Growth Hormone on Haematopoietic Recovery of Rats Receiving Chemotherapy.
Chemotherapy. 2008 Oct 2; 54(6): 447-455
Zhang Y, Chen J, Liang D, Yuan Y, Wu X
Human growth hormone (hGH) is a pleiotropic cytokine targeting a variety of tissues. Its protective effects on haematopoiesis during treatment with chemotherapeutic drugs were investigated. Sprague-Dawley rats were intraperitoneally administered with both carboplatin and 5-fluorouracil together with or without recombinant hGH (rhGH) at a dose of 1 IU/kg/day. Body weight, full blood count, bone marrow differential count and expression of proliferating cell nuclear antigen (PCNA) in bone marrow were measured weekly for 4 weeks in chemotherapy-treated (CT) or chemotherapy plus rhGH-treated (CT+GH) animals. During the first week, body weight, white blood cell count, haematopoietic count and reticulocyte count were decreased in the CT group as well as in the CT+GH group, but to a lesser extent in the latter group (CT vs. CT+GH group, p < 0.05). Further decreases were also prevented in the CT+GH group. Myeloid cells were extremely hypoplastic in the CT group, while in the CT+GH group, myeloid cells recovered from obviously hypoplastic to excessively hyperplastic in the first 2 weeks, and the myeloid karyocyte count increased significantly (CT+GH vs. CT group, p < 0.05). PCNA-positive cell count in the CT+GH group was also significantly higher than in the CT group (CT+GH vs. CT group, p < 0.05). Thus, rhGH showed a promising protective effect on body weight loss and haematopoietic recovery of chemotherapy-treated rats, which may be useful in clinic to reduce the side effects of chemotherapy.