Glufosfamide administered by 1-hour infusion as a second-line treatment for advanced non-small cell lung cancer; a phase II trial of the EORTC-New Drug Development Group.

Abstract

The activity of glufosfamide (beta-D-glucosylisophosphoramide mustard) was tested in a multicentre phase II clinical trial in patients with advanced non-small cell lung cancer (NSCLC) who had received one prior line of platinum-based chemotherapy. Patients were treated with 5000 mg/m(2) glufosfamide by a 1-h intravenous (i.v.) infusion every 3 weeks following registration at the European Organisation for Research and Treatment of Cancer (EORTC) Data Center. Patients were randomised between hydration and no hydration to evaluate the nephroprotective effects of forced diuresis. Patients experiencing >/= 35 micromol/l increase of serum creatinine compared with baseline values were taken off the treatment. The Response evaluation criteria in solid tumours (RECIST) criteria were applied for the response assessment. Blood sampling was performed for a pharmacokinetic analysis. 39 patients from seven institutions were registered and a median of three cycles was given (range 0-6) cycles; 20 patients were randomised to the hydration arm. Haematological toxicity was mild, but treatment-related metabolic and electrolytic abnormalities and increases of serum creatinine occurred in several patients. Hydration did not have any significant influence on the plasma pharmacokinetics of glufosfamide and did not show any nephroprotective effect. Only one confirmed partial remission was observed (response rate 3%; 95% (Confidence Interval (CI) 0-14) and 18 cases with stable disease (49%) were recorded as assessed by an independent panel. Median survival of all patients treated was 5.8 months (95% CI 4.2-7.9). In conclusion, glufosfamide administered by a 1-h infusion every 3 weeks has modest activity in advanced NSCLC patients after one prior platinum-based chemotherapy.

• Authors: G Giaccone, E F Smit, M de Jonge, E Dansin, E Briasoulis, A Ardizzoni, J-Y Douillard, D Spaeth, D Lacombe, B Baron, P Bachmann, P Fumoleau, EORTC-New Drug Development Group
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 40 Issue 5 Pg. 667-72 (Mar 2004) ISSN: 0959-8049 [Print] England
• PMID: 15010066 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antineoplastic Agents
• Phosphoramide Mustards
• beta-D-glucosylisophosphoramide mustard
• Glucose
• Ifosfamide

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Child
• Child, Preschool
• Disease Progression
• Drug Administration Schedule
• Female
• Glucose (analogs & derivatives)
• Humans
• Ifosfamide (analogs & derivatives)
• Infusions, Intravenous
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Phosphoramide Mustards (administration & dosage, adverse effects, pharmacokinetics)
• Prospective Studies