Second-line treatment of small-cell lung cancer with the camptothecin-derivative GI147211: A study of the EORTC Early Clinical Studies Group (ECSG)

Background: GI147211, a 10,11-ethylenedioxy substituted analogue of camptot hecin (CPT), was brought into clinical development because of its higher wa ter solubility and greater potency as compared to topotecan (TPT). The anti tumor activity of GI147211 as second-line therapy in small-cell lung cancer (SCLC) was assessed after stratification of patients in refractory (no res ponse to initial treatment or relapse within three months from last cycle) and chemosensitive (relapse more than three months from last cycle). Patients and methods: Sixty-seven patients were entered in the study and si xty-two were evaluable for response, twenty-eight in the refractory and thi rty-four in the chemosensitive group. All patients had received 1 line of c hemotherapy; 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/m( 2)/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% confid ence 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 th e chemosensitive group. Only partial responses (PR) were observed with a me dian 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 neutr openia (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 agen t for second-line treatment of SCLC; the antitumor activity and toxicity pr ofile are comparable to those observed with TPT which remains the leading C PT analogue for salvage treatment. Interest has been renewed in the clinica l development of GI147211 by preclinical data with the liposomal formulatio n showing an increased therapeutic index.