Search results for "Camptothecin"
showing 10 items of 93 documents
Chemotherapy for advanced gastric cancer
2017
Background Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen. Objectives To assess the effica…
Molecular Docking approach on the Topoisomerase I inhibitors series included in the NCI anti-cancer agents mechanism database
2006
Topoisomerase I (Top1) is an essential enzyme participating to all those processes associated with separation of DNA strands. It manages superhelical tensions through the transient breakage of one strand of duplex DNA, followed by the unwinding of supercoiled DNA. Camptothecins, a class of alkaloids extracted from the wood of a Chinese tree, were found to be potent inhibitors of Topoisomerase I. The National Cancer Institute (NCI) Anti-cancer Agents Mechanism Database contains several camptothecins derivatives, classified as selective Top1 inhibitors. In this work we performed molecular docking studies on 24 camptothecin-like inhibitors present in this database (using Autodock 3.0.5). In or…
Nalidixic acid-resistant V79 cells with reduced DNA topoisomerase II activity and amplification prone phenotype
1992
Spontaneously nalidixic acid-resistant lines (NAr lines) were selected from a V79 Chinese hamster cell line and phenotypically characterized. NAr lines showed an increased doubling time, a higher number of spontaneous SCE, and more interestingly, decreased DNA topoisomerase II activity. These lines were also cross-resistant to the eukaryotic topoisomerase II inhibitors etoposide and adriamycin, but showed the same level of sensitivity as the parental line to the DNA topoisomerase I inhibitor camptothecin. NAr lines were cross-resistant to other drugs, such as PALA, MTX and MPA, resistance to which has been shown to arise by amplification of the target genes. This last feature, together with…
Chemical-Biology of Natural Products from Medicinal Plants for Cancer Therapy
2010
Secondary metabolites are produced by an organism for defense towards competitors, herbivores, and pathogens. They also act as signal compounds to attract animals for pollination and seed dispersal. Fortunately, many secondary metabolites from plants exhibit diverse pharmacological features. Exploitation of these beneficial effects is the primary goal of researchers working in the area of molecular pharmacology of natural products. Natural products are among the major players in pharmacology in general and in cancer therapy in particular. A considerable portion of antitumor agents currently used in the clinic are of natural origin (e.g. Vinca alkaloids, taxanes, podophyllotoxin, camptotheci…
Weekly treatment with irinotecan, folinic acid and infusional 5-fluorouracil (ILF) in patients with advanced gastric cancer.
2003
Although 5-fluorouracil remains the mainstay of treatment for advanced gastric cancer (AGC), no standard chemotherapy regimen exists. Combinations of irinotecan with folinic acid and infusional 5-fluorouracil (5-FU) (ILF) have shown good efficacy with acceptable toxicity in patients with metastatic colorectal cancer. At present, only sparse data on ILF are available for AGC. Therefore we conducted a prospective study of this combination in 25 consecutive patients with metastatic gastric cancer. Median age was 63 years, 10 had received prior chemotherapy and 13 presented initially with peritoneal carcinosis. Treatment consisted of irinotecan 80 mg/m2, folinic acid 500 mg/m2 and infusional 5-…
TRIPLET SCHEDULE OF WEEKLY 5-FLUOROURACIL AND ALTERNATING IRINOTECAN OR OXALIPLATIN IN ADVANCED COLORECTAL CANCER: A DOSE-FINDING AND PHASE II STUDY.
2010
A weekly administration of alternating irinotecan or oxaliplatin associated to 5-Fluorouracil in advanced colorectal cancer was planned in order to evaluate a new schedule maintaining dose intensities of each drug as in double combinations and tolerability of the triplet association. The following weekly schedule was administered: irinotecan, days 1 and 15; oxaliplatin, days 8 and 22; 5-fluorouracil (5-FU) over 12-h (from 10:00 p.m. to 10:00 a.m.) timed flat infusion, days 1-2, 8-9, 15-16 and 22-23, every 4 weeks. Dose- finding and phase II study were planned. Thirteen patients were enrolled in the dose-finding study and 23 in the phase II study. The recommended doses of our study are: irin…
Biweekly oxaliplatin plus irinotecan and folinic acid-modulated 5-fluorouracil: a phase II study in pretreated patients with metastatic colorectal ca…
2006
Oxaliplatin (OXA) and irinotecan (IRI) are active drugs for metastatic colorectal cancer, their toxicity profiles are not overlapping, and both drugs have shown at least additivity with folinic acid-modulated 5-fluorouracil (5FU). We carried out this phase II study to assess the activity and toxicity of a biweekly regimen including OXA plus IRI on day 1, and levo-folinic acid (LFA) plus 5FU on day 2 (OXIRIFAFU) in pretreated patients with metastatic colorectal cancer. Forty-one patients, all previously treated with adjuvant and/or palliative 5FU-based chemotherapy (16 of them already exposed to IRI, OXA or both), were enrolled into this trial. On the basis of sensitivity to previous treatme…
Bevacizumab efficacy in metastatic colorectal cancer is dependent on primary tumor resection.
2014
Purpose Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and second-line metastatic colorectal cancer (mCRC). However, to date, there is no current biomarker predictive for the benefit of bevacizumab use for these patients. Preclinical data suggest that the presence of the primary tumor could be involved in less efficient antitumor activity of antiangiogenic agents, but no clinical data currently support this hypothesis. Methods We performed a retrospective analysis of factors associated with overall survival (OS) in a study cohort of 409 mCRC patients. Univariate and multivariate Cox proportional hazard regression models were used to assess the infl…
Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients
2009
AIM: To investigate the efficacy and safety of cape-citabine plus irinotecan ± bevacizumab in advanced or metastatic colorectal cancer patients. METHODS: Forty six patients with previously untreated, locally-advanced or metastatic colorectal cancer (mCRC) were recruited between 2001-2006 in a prospective open-label phase II trial, in German community-based outpatient clinics. Patients received a standard capecitabine plus irinotecan (CAPIRI) or CAPIRI plus bevacizumab (CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of > grade 2 toxicity. The treatment choice of bevacizumab was at the discretion of the physician. The primary endpoints were respon…
Safety and efficacy of irinotecan plus high-dose leucovorin and intravenous bolus 5-fluorouracil for metastatic colorectal cancer: pooled analysis of…
2005
Abstract Background A biweekly regimen of irinotecan 200 mg/m2 on day 1 and levo-leucovorin (LV) 250 mg/m2 plus 5-fluorouracil (5-FU) 850 mg/m2 via intravenous bolus on day 2 was assessed in 2 consecutive randomized trials in metastatic colorectal cancer (CRC). Patients and Methods Individual data of 254 patients were merged, and baseline features potentially affecting overall response rate (ORR), progression-free survival (PFS),overall survival (OS), and occurrence of severe toxicity were analyzed by univariate and multivariate analyses. Results In the pooled series, ORR was 33% (95% confidence interval [CI], 27%-39%). Liver-only disease (47% vs. 25%; P = 0.0012) and absence of previous we…