Glufosfamide administered using a 1-hour infusion given as first-line treatment for advanced pancreatic cancer. A phase II trial of the EORTC-new drug development group
Φόρτωση...
Ημερομηνία
Συγγραφείς
Briasoulis, E.
Pavlidis, N.
Terret, C.
Bauer, J.
Fiedler, W.
Schoffski, P.
Raoul, J. L.
Hess, D.
Selvais, R.
Lacombe, D.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Eur J Cancer
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
The activity of glufosfamide (beta-D-glucopyranosyl-N,N'-di-(2-chloroethyl)-phosphoric acid diamide) against pancreatic cancer was investigated in a multicentre, phase II clinical study. Chemotherapy-nai;ve patients with advanced or metastatic disease were treated with glufosfamide (5 g/m(2)) using a 1-h intravenous (i.v.) infusion every 3 weeks. Patients were randomised between active-hydration and normal fluids to evaluate the nephroprotective effect of forced diuresis. Patients experiencing >0.4 mg/dl (>35 micromol/l) increase in serum creatinine compared with their baseline value were taken off treatment for safety reasons. The evaluation of response was according to the Response evaluation criteria in solid tumours (RECIST). Blood sampling was performed for pharmacokinetic analyses. 35 patients from 13 institutions were registered over a 13-month period. A total of 114 treatment cycles (median 3, range 1-8) were administered to 34 patients; 18 patients were allocated to the hydration arm. Overall haematological toxicity was mild. Metabolic acidosis occurred in 2 patients treated in the active-hydration arm, grade 3 hypokalaemia was recorded in 5 patients and grade 3 hypophosphataemia in 4 patients. One patient had a grade 4 increase in serum creatinine level, concomitantly to disease progression. Active-hydration did not show a nephroprotective effect and the plasma pharmacokinetics (Pk) of glufosfamide was not significantly influenced by hydration. Two confirmed partial remissions (PR) were reported (response rate 5.9%, 95% Confidence Interval (CI) 0.7-19.7%) and 11 cases obtained disease stabilisation (32.4%). An extra mural review panel confirmed all of the responses. Median overall survival was 5.3 months (95% CI 3.9-7.1) and time to progression (TTP) was 1.4 months (95% CI 1.3-2.7). In conclusion, glufosfamide administered using a 1-h infusion every 3 weeks has a modest activity in advanced pancreatic adenocarcinoma. Haematological toxicity is particularly mild, but regular monitoring of renal function is recommended.
Περιγραφή
Λέξεις-κλειδιά
Adenocarcinoma/*drug therapy, Adult, Aged, Antineoplastic Agents/*administration & dosage/adverse effects/pharmacokinetics, Disease Progression, Disease-Free Survival, Female, Glucose/analogs & derivatives, Humans, Ifosfamide/analogs & derivatives, Infusions, Intravenous, Male, Middle Aged, Pancreatic Neoplasms/*drug therapy, Phosphoramide Mustards/*administration & dosage/adverse effects/pharmacokinetics, Prospective Studies, Treatment Outcome
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/14556925
http://ac.els-cdn.com/S0959804903006294/1-s2.0-S0959804903006294-main.pdf?_tid=05b9b2b6ce8eed635fd141cf9fb66f09&acdnat=1333702811_8b856e6815e294d62b882fbb20543193
http://ac.els-cdn.com/S0959804903006294/1-s2.0-S0959804903006294-main.pdf?_tid=05b9b2b6ce8eed635fd141cf9fb66f09&acdnat=1333702811_8b856e6815e294d62b882fbb20543193
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής