Abstract |
Two multicentre phase II trials were designed to determine if tumour responses can be achieved in progressive small-cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC) patients treated with ISIS 5132, an inhibitor of C- raf kinase mRNA expression ( CGP 69846A; ISIS Pharmaceuticals Inc, Carlsbad, CA), and to further characterise the safety of the compound. Between August 1998 and November 1999, 26 patients (18 NSCLC, 8 SCLC) were entered. Out of these, 23 were eligible, 22 (18 NSCLC, 4 SCLC) were treated with ISIS 5132 (2 mg/kg/day, 21 days continuous intravenous (i.v.) infusion every 4 weeks) and were evaluable for toxicity and 18 (15 NSCLC, 3 SCLC) were evaluable for efficacy. For the whole group haematological toxicity did not exceed grade 2. One patient experienced a grade 4 increased prothrombin time. Non-haematological toxicity was mild to moderate, with the observation of asthenia and nausea and vomiting. Progressive disease (PD) was diagnosed in 10 patients (8 NSCLC and 2 SCLC). 8 more patients (7 NSCLC, 1 SCLC) were considered as treatment failures. In conclusion, this study using ISIS 5132 with this dose and schedule of administration excludes a 20% response rate with 95% confidence intervals for NSCLC and cannot draw any conclusions for SCLC patients as only a few were involved in the study.
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Authors | B Coudert, A Anthoney, W Fiedler, J P Droz, V Dieras, M Borner, J F Smyth, R Morant, M J de Vries, M Roelvink, P Fumoleau, European Organization for Research and Treatment of Cancer (EORTC) |
Journal | European journal of cancer (Oxford, England : 1990)
(Eur J Cancer)
Vol. 37
Issue 17
Pg. 2194-8
(Nov 2001)
ISSN: 0959-8049 [Print] England |
PMID | 11677106
(Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study)
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Chemical References |
- Antineoplastic Agents
- Enzyme Inhibitors
- Oligodeoxyribonucleotides, Antisense
- Thionucleotides
- ISIS 5132
- Proto-Oncogene Proteins c-raf
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Topics |
- Adult
- Aged
- Antineoplastic Agents
(adverse effects, therapeutic use)
- Carcinoma, Non-Small-Cell Lung
(drug therapy)
- Carcinoma, Small Cell
(drug therapy)
- Disease Progression
- Drug Administration Schedule
- Enzyme Inhibitors
(adverse effects, therapeutic use)
- Female
- Hematologic Diseases
(chemically induced)
- Humans
- Lung Neoplasms
(drug therapy)
- Male
- Middle Aged
- Oligodeoxyribonucleotides, Antisense
(adverse effects, therapeutic use)
- Proto-Oncogene Proteins c-raf
(antagonists & inhibitors)
- Thionucleotides
(adverse effects, therapeutic use)
- Treatment Outcome
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