The Experts below are selected from a list of 135 Experts worldwide ranked by ideXlab platform
Jan H.m. Schellens - One of the best experts on this subject based on the ideXlab platform.
-
Organic anion-transporting polypeptide 1B1 mediates transport of Gimatecan and BNP1350 and can be inhibited by several classic ATP-binding cassette (ABC) B1 and/or ABCG2 inhibitors.
Drug Metabolism and Disposition, 2009Co-Authors: Roos L. Oostendorp, Cornelia M.m. Van Der Kruijssen, Kathryn E. Kenworthy, Evita Van De Steeg, Alfred H Schinkel, Jos H. Beijnen, Jan H.m. SchellensAbstract:Organic anion-transporting polypeptides (OATPs) are important uptake transporters that can have a profound impact on the systemic pharmacokinetics, tissue distribution, and elimination of several drugs. Previous in vivo studies of the pharmacokinetics of the lipophilic camptothecin (CPT) analog gimatecan suggested that the ATP-binding cassette (ABC) B1 (P-glycoprotein) and/or ABCG2 (breast cancer resistance protein) inhibitors elacridar and pantoprazole could inhibit transporters other than ABCB1 and ABCG2. In this study, we tested the possible role of OATP1B1 in this interaction by screening a number of CPT analogs for their transport affinity by human OATP1B1 in vitro. In addition, the impact of several widely used ABCB1 and/or ABCG2 modulators on this OATP1B1-mediated transport was assessed. We identified two novel CPT anticancer drugs, gimatecan and BNP1350, as OATP1B1 substrates, whereas irinotecan, topotecan, and Lurtotecan were not transported by OATP1B1. It is interesting to note that transport of 17β-estradiol 17β-d-glucuronide (control), gimatecan, and BNP1350 by OATP1B1 could be completely inhibited by the classic ABCB1 and/or ABCG2 inhibitors elacridar, valspodar, pantoprazole, and, to a lesser extent, zosuquidar and verapamil. Therefore, the effect of these ABCB1 and ABCG2 modulators on the plasma pharmacokinetics of gimatecan and BNP1350 (and possibly also other OATP1B1 substrates) may be partly because of inhibition of OATP1B1 besides inhibition of ABCB1 and/or ABCG2. The findings of this study suggest that OATP1B1 polymorphisms or coadministration with one of the ABCB1/ABCG2 inhibitors could affect drug uptake, tissue distribution, and elimination of some CPT anticancer drugs, thereby modifying their efficacy and/or safety profile.
-
Organic Anion-Transporting Polypeptide 1B1 Mediates Transport of Gimatecan and BNP1350 and Can Be Inhibited by Several Classic ATP-Binding Cassette (ABC) B1 and/or ABCG2 Inhibitors
Drug metabolism and disposition: the biological fate of chemicals, 2009Co-Authors: Roos L. Oostendorp, Kathryn E. Kenworthy, Alfred H Schinkel, Jos H. Beijnen, Evita Van De Steeg, Cornelia M.m. Van Der Kruijssen, Jan H.m. SchellensAbstract:Organic anion-transporting polypeptides (OATPs) are important uptake transporters that can have a profound impact on the systemic pharmacokinetics, tissue distribution, and elimination of several drugs. Previous in vivo studies of the pharmacokinetics of the lipophilic camptothecin (CPT) analog gimatecan suggested that the ATP-binding cassette (ABC) B1 (P-glycoprotein) and/or ABCG2 (breast cancer resistance protein) inhibitors elacridar and pantoprazole could inhibit transporters other than ABCB1 and ABCG2. In this study, we tested the possible role of OATP1B1 in this interaction by screening a number of CPT analogs for their transport affinity by human OATP1B1 in vitro. In addition, the impact of several widely used ABCB1 and/or ABCG2 modulators on this OATP1B1-mediated transport was assessed. We identified two novel CPT anticancer drugs, gimatecan and BNP1350, as OATP1B1 substrates, whereas irinotecan, topotecan, and Lurtotecan were not transported by OATP1B1. It is interesting to note that transport of 17beta-estradiol 17beta-d-glucuronide (control), gimatecan, and BNP1350 by OATP1B1 could be completely inhibited by the classic ABCB1 and/or ABCG2 inhibitors elacridar, valspodar, pantoprazole, and, to a lesser extent, zosuquidar and verapamil. Therefore, the effect of these ABCB1 and ABCG2 modulators on the plasma pharmacokinetics of gimatecan and BNP1350 (and possibly also other OATP1B1 substrates) may be partly because of inhibition of OATP1B1 besides inhibition of ABCB1 and/or ABCG2. The findings of this study suggest that OATP1B1 polymorphisms or coadministration with one of the ABCB1/ABCG2 inhibitors could affect drug uptake, tissue distribution, and elimination of some CPT anticancer drugs, thereby modifying their efficacy and/or safety profile.
-
Topoisomerase I inhibitors in the treatment of gastrointestinal cancer: from intravenous to oral administration.
Clinical colorectal cancer, 2004Co-Authors: Isa E.l.m. Kuppens, Jos H. Beijnen, Jan H.m. SchellensAbstract:This article reviews the current status of the topoisomerase I (top I) inhibitors in the treatment of gastrointestinal (GI) malignancies. We focus on oral drug administration, the mode of administration that is generally preferred by patients with cancer. However, the great majority of the studies have been performed with intravenous (I.V.) administration. The most extensively investigated GI malignancy in phase I/II studies is colorectal cancer (CRC), for which I.V. irinotecan is currently approved in the United States and Europe. We discuss the activity and efficacy of irinotecan as a single agent in CRC and in combination regimens. Also, results obtained with monotherapy and in combination treatment in other GI malignancies such as esophageal, gastric, and pancreatic cancer are discussed. Few phase I studies have been performed with oral irinotecan and its clinical activity has not yet been fully determined. Several top I inhibitors are discussed, including topotecan, 9-aminocamptothecin, rubitecan, exatecan, and Lurtotecan. None of these agents, given orally or intravenously, have shown activity in CRC similar to that of I.V. irinotecan. However, several agents show promising results in other GI malignancies, eg, rubitecan and exatecan in pancreatic cancer. A complicating factor in the oral administration of the top I inhibitors is the often encountered low and variable oral bioavailability. This can partly be explained by the high affinity for the drug efflux pumps BCRP (ABCG2) and P-glycoprotein, which are highly expressed in the epithelial apical membrane of the GI tract. A novel approach to improve the oral bioavailability of the top I inhibitors by temporary blockade of the drug transporter BCRP is described.
-
Clinical pharmacokinetics of camptothecin topoisomerase I inhibitors.
Pharmacy World and Science, 1998Co-Authors: Virginie M.m. Herben, Jos H. Beijnen, Wim W. Ten Bokkel Huinink, Jan H.m. SchellensAbstract:In this review the clinical pharmacokinetics of camptothecin topoisomerase I inhibitors, an important new class of anticancer drugs, is discussed. Two prototypes, topotecan and irinotecan, are currently marketed in many European countries and the USA for the treatment of patients with ovarian and colorectal cancer, respectively. Other camptothecin derivatives, including Lurtotecan, 9‐aminocamptothecin (9‐AC) and 9‐nitrocamptothecin (9‐NC), are at different stages of clinical development. The common property of camptothecin analogues is their action against DNA topoisomerase I, but beyond this similarity the compounds differ widely in terms of antitumour efficacy, pharmacology, pharmacokinetics and metabolism. We review chemistry, mechanism of action, stability and bioanalysis of the camptothecins. Dosage and administration, status of clinical application, pharmacokinetics, pharmacodynamics and drug interactions are discussed.
M. Ptaszynski - One of the best experts on this subject based on the ideXlab platform.
-
Randomized phase II parallel evaluation of OSI-211 (liposomal Lurtotecan) and topotecan in women with relapsed epithelial ovarian cancer (EOC)
Journal of Clinical Oncology, 2005Co-Authors: Christopher J. Poole, C. Van Duym, H. Thomas, M. E. Gore, Graham Dark, P. A. Vasey, N P Bailey, Terri Cameron, M. PtaszynskiAbstract:5017 Background: OSI-211 is a liposomal formulation of Lurtotecan, a topoisomerase-I inhibitor. In a previous randomised dose ranging/feasibility trial a day 1, 2, and 3 q 3/52 regimen was chosen f...
-
A phase 1 study of OSI-211 given as an intravenous infusion days 1, 2, and 3 every three weeks in patients with solid cancers
Investigational New Drugs, 2004Co-Authors: K. Gelmon, M. Hamilton, M. Ptaszynski, H. Hirte, B. Fisher, W. Walsh, N. Onetto, E. EisenhauerAbstract:Purpose: To define the maximum tolerated dose (MTD), recommended phase II dose (RD) and dose limiting toxicity (DLT) of liposomal Lurtotecan, OSI-211 (formerly known as NX211), given as a short intravenous infusion on days 1, 2, and 3 every three weeks. Experimental design: Thirty-seven patients were enrolled and treated in a dose escalation study from a starting dose of 0.15 mg/m^2 daily × 3 to 2.1 mg/m^2 daily × 3. Detailed pharmacokinetic analyses of blood were done on both days 1 and 3 of the first cycle and toxicity was monitored. Results: Two MTDs were defined; one for patients defined as minimally pretreated and one for those heavily pretreated. Dose limiting toxicity was myelosuppression: primarily thrombocytopenia although neutropenia was also noted. The MTD was 2.1 mg/m^2/d (total dose of 6.3 mg/m^2) in minimally pretreated patients and 1.8 mg/m^2/d (5.4 mg/m^2 total dose) in heavily pretreated patients. Pharmacokinetics revealed that AUC and C _max increased with dose and were significantly higher than that of free Lurtotecan (AUC approx. 100 fold higher). The half life and duration of the active lactone form were also significantly longer than historical data on free drug. Two partial responses were seen, one each in a patient with breast and ovarian cancer. Conclusions: Two Phase II recommended doses were established for OSI-211 given as a daily × 3 schedule every three weeks. The recommended phase II dose is 1.8 mg/m^2 daily × 3 for minimally pretreated patients and 1.5 mg/m^2 for those heavily pretreated. Phase II studies should be initiated in sensitive tumours.
-
A phase I study of OSI-211 and cisplatin as intravenous infusions given on days 1, 2 and 3 every 3 weeks in patients with solid cancers
Annals of oncology : official journal of the European Society for Medical Oncology, 2004Co-Authors: M. J. Mackenzie, M. Ptaszynski, K. Gelmon, H. Hirte, B. Fisher, Lillian L. Siu, Elizabeth A. EisenhauerAbstract:Abstract Background OSI-211 (also known as NX211) is a liposomal preparation of the topoisomerase I inhibitor, Lurtotecan, which has shown antitumor activity in phase I and II clinical trials. Cisplatin is a widely used antineoplastic agent with activity in a broad range of tumor types. This phase I trial was conducted to determine the recommended doses of these agents, and their pharmacokinetic properties and toxicities in patients with advanced solid malignancies. Patients and methods Fourteen patients with advanced and/or metastatic solid malignancies were enrolled in this trial. The first planned dose level was OSI-211 0.9 mg/m2 with cisplatin 25 mg/m2 administered intravenously daily for the first three consecutive days of a 21-day cycle. Patients were evaluated for hematological and non-hematological toxicities, and pharmacokinetic studies were performed on both agents. Results The recommended phase II dose was determined to be 0.7 mg/m2 OSI-211 given with 25 mg/m2 cisplatin. Dose-limiting neutropenia was seen in two of three patients at the starting dose level. Three of 11 patients at the second (lower) dose level experienced dose-limiting thrombocytopenia; febrile neutropenia was also seen in one patient. Non-hematological toxicities were generally manageable and included fatigue, nausea and vomiting. Considerable variability was seen in both hematological toxicities and pharmacokinetics. One complete response and three partial responses were seen. Conclusions The recommended phase II dose for this combination is 0.7 mg/m2 OSI-211 with 25 mg/m2 cisplatin given as an intravenous infusion on days 1, 2 and 3 of a 21-day cycle. The main toxicity was myelosuppression. Preliminary evidence of antitumor activity was seen.
Emma Barrett - One of the best experts on this subject based on the ideXlab platform.
-
Phase I study of OSI-211 (liposomal Lurtotecan) in combination with liposomal doxorubicin (LD) every 3 weeks in patients (pts) with advanced solid tumors; final analysis suggests benefit in refractory ovarian cancer (OC)
Journal of Clinical Oncology, 2005Co-Authors: D. S. Mendelson, Emma Barrett, Molly Brewer, Milos J. Janicek, E. Breitenbach, M. Hamilton, M. Ptazynski, C. Van Duym, Michael S. GordonAbstract:2074 Background: OSI-211 is a topoisomerase (topo) I inhibitor in liposomal formulation. In vivo efficacy of the liposomal preparation is greater than native Lurtotecan or topotecan and allows comb...
-
Phase I and Pharmacokinetic Study of a Low-Clearance, Unilamellar Liposomal Formulation of Lurtotecan, a Topoisomerase 1 Inhibitor, in Patients with Advanced Leukemia
Cancer, 2004Co-Authors: Francis J. Giles, Marta Hamilton, Emma Barrett, Martin S. Tallman, Guillermo Garcia-manero, Jorge E. Cortes, Deborah A. Thomas, William G. Wierda, Srdan Verstovsek, Maher AlbitarAbstract:BACKGROUND OSI-211 is a low-clearance, unilamellar liposomal formulation of a water-soluble camptothecin analogue, Lurtotecan. OSI-211 has significant activity in severe combined immunodeficient mouse models of human leukemia. METHODS This study was conducted to define the dose-limiting toxicities (DLT) and pharmacokinetics of OSI-211 in patients with refractory myeloid leukemias. Patients with refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP) were eligible. OSI-211 was given as an intravenous infusion over 30 minutes daily for 3 days. The starting dose was 1.5 mg/m2 per day (4.5 mg/m2 per course). The dose was escalated by 50% until Grade 2 toxicity was observed and then by 30–35% until the DLT was defined. Serial plasma and urine samples were collected, and drug levels were determined by high-performance liquid chromatography with fluorescence detection. RESULTS Twenty patients (18 patients [90%] with AML, and 1 patient each [5%] with MDS and CML-BP) were treated. Mucositis and diarrhea were considered to be the DLTs. The maximum tolerated dose was 3.7 mg/m2 per day. Fourteen of 18 evaluable patients (78%) with AML or MDS achieved transient bone marrow aplasia. The mean systemic clearance of Lurtotecan in plasma was 0.946 ± 1.53 L/hour/m2. Urinary recovery of Lurtotecan was 6.66% ± 5.26% (range, 1.05–18.4%). CONCLUSIONS Liposomal encapsulation of Lurtotecan altered its metabolism significantly. There was no evident correlation between exposure, as measured by plasma pharmacokinetics of Lurtotecan, and clinical response or toxicities. OSI-211 merits further study in hematologic malignancies. Cancer 2004;100:1449–58. © 2004 American Cancer Society.
-
A phase II study of liposomal Lurtotecan (OSI-211) in patients with topotecan resistant ovarian cancer.
Gynecologic oncology, 2004Co-Authors: Michael V. Seiden, Franco M. Muggia, Allan Astrow, Ursula A. Matulonis, S. M. Campos, Maria Roche, Julia Sivret, Jason Rusk, Emma BarrettAbstract:Abstract Objective . To determine the safety and efficacy of a novel topoisomerase I inhibitor, liposomal Lurtotecan, in patients with topotecan resistant ovarian cancer. Methods . The trial was an open-label phase II study for patients stratified by resistance to either single agent topotecan or to a prior topotecan-containing regimen. Liposomal Lurtotecan was delivered at a dose of 2.4 mg/m 2 on Days 1 and 8 of a 21-day cycle. Dose escalations and reductions were allowed based on hematologic toxicity. Patients were evaluated every two cycles for response to liposomal Lurtotecan. Results . Twenty-two women were accrued, with 16 women resistant to single agent topotecan and 6 women resistant to topotecan given in combination with a second chemotherapy agent. Hematologic toxicity consisted of mild to moderate thrombocytopenia, anemia, and neutropenia with mild to moderate gastrointestinal toxicity and fatigue. There were no responses, although eight patients had stable disease. Conclusions . Liposomal Lurtotecan at this schedule demonstrates moderate hematologic toxicity and no evidence of clinical activity in a group of heavily pretreated women previously exposed to the topoisomerase I inhibitor topotecan. The study of this agent in alternative patient populations or with alternative schedules is ongoing.
Jos H. Beijnen - One of the best experts on this subject based on the ideXlab platform.
-
Organic anion-transporting polypeptide 1B1 mediates transport of Gimatecan and BNP1350 and can be inhibited by several classic ATP-binding cassette (ABC) B1 and/or ABCG2 inhibitors.
Drug Metabolism and Disposition, 2009Co-Authors: Roos L. Oostendorp, Cornelia M.m. Van Der Kruijssen, Kathryn E. Kenworthy, Evita Van De Steeg, Alfred H Schinkel, Jos H. Beijnen, Jan H.m. SchellensAbstract:Organic anion-transporting polypeptides (OATPs) are important uptake transporters that can have a profound impact on the systemic pharmacokinetics, tissue distribution, and elimination of several drugs. Previous in vivo studies of the pharmacokinetics of the lipophilic camptothecin (CPT) analog gimatecan suggested that the ATP-binding cassette (ABC) B1 (P-glycoprotein) and/or ABCG2 (breast cancer resistance protein) inhibitors elacridar and pantoprazole could inhibit transporters other than ABCB1 and ABCG2. In this study, we tested the possible role of OATP1B1 in this interaction by screening a number of CPT analogs for their transport affinity by human OATP1B1 in vitro. In addition, the impact of several widely used ABCB1 and/or ABCG2 modulators on this OATP1B1-mediated transport was assessed. We identified two novel CPT anticancer drugs, gimatecan and BNP1350, as OATP1B1 substrates, whereas irinotecan, topotecan, and Lurtotecan were not transported by OATP1B1. It is interesting to note that transport of 17β-estradiol 17β-d-glucuronide (control), gimatecan, and BNP1350 by OATP1B1 could be completely inhibited by the classic ABCB1 and/or ABCG2 inhibitors elacridar, valspodar, pantoprazole, and, to a lesser extent, zosuquidar and verapamil. Therefore, the effect of these ABCB1 and ABCG2 modulators on the plasma pharmacokinetics of gimatecan and BNP1350 (and possibly also other OATP1B1 substrates) may be partly because of inhibition of OATP1B1 besides inhibition of ABCB1 and/or ABCG2. The findings of this study suggest that OATP1B1 polymorphisms or coadministration with one of the ABCB1/ABCG2 inhibitors could affect drug uptake, tissue distribution, and elimination of some CPT anticancer drugs, thereby modifying their efficacy and/or safety profile.
-
Organic Anion-Transporting Polypeptide 1B1 Mediates Transport of Gimatecan and BNP1350 and Can Be Inhibited by Several Classic ATP-Binding Cassette (ABC) B1 and/or ABCG2 Inhibitors
Drug metabolism and disposition: the biological fate of chemicals, 2009Co-Authors: Roos L. Oostendorp, Kathryn E. Kenworthy, Alfred H Schinkel, Jos H. Beijnen, Evita Van De Steeg, Cornelia M.m. Van Der Kruijssen, Jan H.m. SchellensAbstract:Organic anion-transporting polypeptides (OATPs) are important uptake transporters that can have a profound impact on the systemic pharmacokinetics, tissue distribution, and elimination of several drugs. Previous in vivo studies of the pharmacokinetics of the lipophilic camptothecin (CPT) analog gimatecan suggested that the ATP-binding cassette (ABC) B1 (P-glycoprotein) and/or ABCG2 (breast cancer resistance protein) inhibitors elacridar and pantoprazole could inhibit transporters other than ABCB1 and ABCG2. In this study, we tested the possible role of OATP1B1 in this interaction by screening a number of CPT analogs for their transport affinity by human OATP1B1 in vitro. In addition, the impact of several widely used ABCB1 and/or ABCG2 modulators on this OATP1B1-mediated transport was assessed. We identified two novel CPT anticancer drugs, gimatecan and BNP1350, as OATP1B1 substrates, whereas irinotecan, topotecan, and Lurtotecan were not transported by OATP1B1. It is interesting to note that transport of 17beta-estradiol 17beta-d-glucuronide (control), gimatecan, and BNP1350 by OATP1B1 could be completely inhibited by the classic ABCB1 and/or ABCG2 inhibitors elacridar, valspodar, pantoprazole, and, to a lesser extent, zosuquidar and verapamil. Therefore, the effect of these ABCB1 and ABCG2 modulators on the plasma pharmacokinetics of gimatecan and BNP1350 (and possibly also other OATP1B1 substrates) may be partly because of inhibition of OATP1B1 besides inhibition of ABCB1 and/or ABCG2. The findings of this study suggest that OATP1B1 polymorphisms or coadministration with one of the ABCB1/ABCG2 inhibitors could affect drug uptake, tissue distribution, and elimination of some CPT anticancer drugs, thereby modifying their efficacy and/or safety profile.
-
Topoisomerase I inhibitors in the treatment of gastrointestinal cancer: from intravenous to oral administration.
Clinical colorectal cancer, 2004Co-Authors: Isa E.l.m. Kuppens, Jos H. Beijnen, Jan H.m. SchellensAbstract:This article reviews the current status of the topoisomerase I (top I) inhibitors in the treatment of gastrointestinal (GI) malignancies. We focus on oral drug administration, the mode of administration that is generally preferred by patients with cancer. However, the great majority of the studies have been performed with intravenous (I.V.) administration. The most extensively investigated GI malignancy in phase I/II studies is colorectal cancer (CRC), for which I.V. irinotecan is currently approved in the United States and Europe. We discuss the activity and efficacy of irinotecan as a single agent in CRC and in combination regimens. Also, results obtained with monotherapy and in combination treatment in other GI malignancies such as esophageal, gastric, and pancreatic cancer are discussed. Few phase I studies have been performed with oral irinotecan and its clinical activity has not yet been fully determined. Several top I inhibitors are discussed, including topotecan, 9-aminocamptothecin, rubitecan, exatecan, and Lurtotecan. None of these agents, given orally or intravenously, have shown activity in CRC similar to that of I.V. irinotecan. However, several agents show promising results in other GI malignancies, eg, rubitecan and exatecan in pancreatic cancer. A complicating factor in the oral administration of the top I inhibitors is the often encountered low and variable oral bioavailability. This can partly be explained by the high affinity for the drug efflux pumps BCRP (ABCG2) and P-glycoprotein, which are highly expressed in the epithelial apical membrane of the GI tract. A novel approach to improve the oral bioavailability of the top I inhibitors by temporary blockade of the drug transporter BCRP is described.
-
Clinical pharmacokinetics of camptothecin topoisomerase I inhibitors.
Pharmacy World and Science, 1998Co-Authors: Virginie M.m. Herben, Jos H. Beijnen, Wim W. Ten Bokkel Huinink, Jan H.m. SchellensAbstract:In this review the clinical pharmacokinetics of camptothecin topoisomerase I inhibitors, an important new class of anticancer drugs, is discussed. Two prototypes, topotecan and irinotecan, are currently marketed in many European countries and the USA for the treatment of patients with ovarian and colorectal cancer, respectively. Other camptothecin derivatives, including Lurtotecan, 9‐aminocamptothecin (9‐AC) and 9‐nitrocamptothecin (9‐NC), are at different stages of clinical development. The common property of camptothecin analogues is their action against DNA topoisomerase I, but beyond this similarity the compounds differ widely in terms of antitumour efficacy, pharmacology, pharmacokinetics and metabolism. We review chemistry, mechanism of action, stability and bioanalysis of the camptothecins. Dosage and administration, status of clinical application, pharmacokinetics, pharmacodynamics and drug interactions are discussed.
C. Van Duym - One of the best experts on this subject based on the ideXlab platform.
-
Phase I study of OSI-211 (liposomal Lurtotecan) in combination with liposomal doxorubicin (LD) every 3 weeks in patients (pts) with advanced solid tumors; final analysis suggests benefit in refractory ovarian cancer (OC)
Journal of Clinical Oncology, 2005Co-Authors: D. S. Mendelson, Emma Barrett, Molly Brewer, Milos J. Janicek, E. Breitenbach, M. Hamilton, M. Ptazynski, C. Van Duym, Michael S. GordonAbstract:2074 Background: OSI-211 is a topoisomerase (topo) I inhibitor in liposomal formulation. In vivo efficacy of the liposomal preparation is greater than native Lurtotecan or topotecan and allows comb...
-
Randomized phase II parallel evaluation of OSI-211 (liposomal Lurtotecan) and topotecan in women with relapsed epithelial ovarian cancer (EOC)
Journal of Clinical Oncology, 2005Co-Authors: Christopher J. Poole, C. Van Duym, H. Thomas, M. E. Gore, Graham Dark, P. A. Vasey, N P Bailey, Terri Cameron, M. PtaszynskiAbstract:5017 Background: OSI-211 is a liposomal formulation of Lurtotecan, a topoisomerase-I inhibitor. In a previous randomised dose ranging/feasibility trial a day 1, 2, and 3 q 3/52 regimen was chosen f...
