title: Second-line treatment of small-cell lung cancer with the camptothecin-derivative GI147211: a study of the EORTC Early Clinical Studies Group (ECSG).
abstract: BACKGROUND
  GI147211, a 10,11-ethylenedioxy substituted analogue of camptothecin (CPT), was brought into clinical development because of its higher water solubility and greater potency as compared to topotecan (TPT). The antitumor activity of GI147211 as second-line therapy in small-cell lung cancer (SCLC) was assessed after stratification of patients in refractory (no response to initial treatment or relapse within three months from last cycle) and chemosensitive (relapse more than three months from last cycle).
  
  
  METHODS
  Sixty-seven patients were entered in the study and sixty-two were evaluable for response, twenty-eight in the refractory and thirty-four in the chemosensitive group. All patients had received 1 line of chemotherapy; radiation had also been given in 29 cases, 6 in the refractory and 23 in the chemosensitive group. GI147211 was administered at 1.2 mg/m2/day as 30-min infusion for five consecutive days every three weeks.
  
  
  RESULTS
  The overall response rate was 16.6% (11 of 66 patients; 95% confidence interval (95% CI): 8.5%-27.5%), 10.3% (3 of 29 patients; 95% CI: 2.2%-27%) in the refractory and 21.1% (8 of 37 patients; 95% CI: 9.5%-37%) in the chemosensitive group. Only partial responses (PR) were observed with a median duration of PR of 4.8 months (5.7 months in the refractory and 5.2 in the chemosensitive group). Hematological toxicity consisted mainly of neutropenia (grades 3-4 in 25% of cycles) and thrombocytopenia (grades 3-4 in 23% of cycles); non-hematological toxicity was mild to moderate and consisted of nausea (22% of cycles), vomiting (11%), malaise (34%).
  
  
  CONCLUSIONS
  At the dose and schedule tested GI147211 is an active new agent for second-line treatment of SCLC; the antitumor activity and toxicity profile are comparable to those observed with TPT which remains the leading CPT analogue for salvage treatment. Interest has been renewed in the clinical development of GI147211 by preclinical data with the liposomal formulation showing an increased therapeutic index.
authors.affiliation: EORTC Early Clinical Studies Group, Amsterdam, The Netherlands. csessa@ticino.com
authors.forename: C
authors.initials: C
authors.lastname: Sessa
authors.forename: J
authors.initials: J
authors.lastname: Wanders
authors.forename: M
authors.initials: M
authors.lastname: Roelvink
authors.forename: P
authors.initials: P
authors.lastname: Dombernowsky
authors.forename: D
authors.initials: D
authors.lastname: Nielsen
authors.forename: R
authors.initials: R
authors.lastname: Morant
authors.forename: P
authors.initials: P
authors.lastname: Drings
authors.forename: P
authors.initials: P
authors.lastname: Wissel
authors.forename: A R
authors.initials: AR
authors.lastname: Hanauske
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016001:Confidence Intervals; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C091719:lurtotecan; D002166:Camptothecin