title: Phase II trial with ISIS 5132 in patients with small-cell (SCLC) and non-small cell (NSCLC) lung cancer. A European Organization for Research and Treatment of Cancer (EORTC) Early Clinical Studies Group report.
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.
authors.affiliation: Centre GF Leclerc BP 77980, 21079 Dijon Cedex, France. bcoudert@dijon.fnclcc.fr
authors.forename: B
authors.initials: B
authors.lastname: Coudert
authors.forename: A
authors.initials: A
authors.lastname: Anthoney
authors.forename: W
authors.initials: W
authors.lastname: Fiedler
authors.forename: J P
authors.initials: JP
authors.lastname: Droz
authors.forename: V
authors.initials: V
authors.lastname: Dieras
authors.forename: M
authors.initials: M
authors.lastname: Borner
authors.forename: J F
authors.initials: JF
authors.lastname: Smyth
authors.forename: R
authors.initials: R
authors.lastname: Morant
authors.forename: M J
authors.initials: MJ
authors.lastname: de Vries
authors.forename: M
authors.initials: M
authors.lastname: Roelvink
authors.forename: P
authors.initials: P
authors.lastname: Fumoleau
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D018450:Disease Progression; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020319:Oligodeoxyribonucleotides, Antisense / Q000009:adverse effects / Q000627:therapeutic use*; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors; D013873:Thionucleotides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D020319:Oligodeoxyribonucleotides, Antisense; D013873:Thionucleotides; C099587:ISIS 5132; D019908:Proto-Oncogene Proteins c-raf