title: A phase II trial of 9-aminocaptothecin (9-AC) as a 120-h infusion in patients with non-small cell lung cancer.
abstract: In a previous phase II trial of the synthetic topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), given as a 72-h infusion, we identified modest single agent activity of 9% in patients with previously untreated advanced non-small cell lung cancer (NSCLC). Preclinical studies suggested that a more prolonged continuous infusion of the drug might lead to greater antitumor activity. A phase I study recommended a phase II dose of 25 microg/m2/hr for 120 h (3000 microg/m2 over 5 days), administered for 2 consecutive weeks of a 3-week cycle. We utilized this schedule and enrolled 13 chemotherapy-naïve patients with Stage IIIB and IV NSCLC in this trial: median age 67 (range 57-74); 46% male; 92% stage IV; and median performance status 1. Twelve patients are available for response and toxicity evaluation after 2 cycles of therapy. One patient achieved a partial response. Four patients had stable disease while seven patients had progressive disease. Patients with stable or progressive disease after two cycles received no additional 9-AC, and were offered conventional chemotherapy. The median survival time was 10.2 months and the one-year survival rate 28% (95% confidence interval, 5-58%). Significant toxicities included myelosuppression, fatigue, and anorexia. One patient had grade 4 neutropenia following the first week of cycle 2, and did not receive additional therapy. There were no neutropenia-related infections. These data suggest that this prolonged schedule is unlikely to increase 9-AC's very modest activity in NSCLC above that seen with the simpler 72-h administration schedule. Further evaluation of 9-AC in NSCLC is not recommended.
authors.affiliation: Department of Medicine and Cancer Research Center, University of Chicago, IL, USA. evokes@medicine.bsd.uchicago.edu
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
authors.forename: G S
authors.initials: GS
authors.lastname: Gordon
authors.forename: C M
authors.initials: CM
authors.lastname: Rudin
authors.forename: A M
authors.initials: AM
authors.lastname: Mauer
authors.forename: S
authors.initials: S
authors.lastname: Watson
authors.forename: S
authors.initials: S
authors.lastname: Krauss
authors.forename: R
authors.initials: R
authors.lastname: Arrieta
authors.forename: H M
authors.initials: HM
authors.lastname: Golomb
authors.forename: P C
authors.initials: PC
authors.lastname: Hoffman
mesh_terms: 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 / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D013997:Time Factors; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D016179:Granulocyte Colony-Stimulating Factor; C080125:9-aminocamptothecin; D002166:Camptothecin