title: Rationale and dose-finding studies of the combination of irinotecan and a taxane on a weekly schedule.
abstract: Cisplatin (Platinol)-based chemotherapy has been the standard systemic therapy for both non-small-cell and small-cell lung cancer for the past 2 decades, though the efficacy and benefit remain modest. Recently, several novel agents have been introduced that have single-agent activity comparable to cisplatin and offer the possibility of improved therapy for lung cancer. Camptothecin and taxane derivatives are associated with both different mechanisms of action and nonhematologic toxicities, and have demonstrated additive or synergistic activity when used in combination in preclinical studies. We review pertinent clinical studies of these agents in lung cancer and present our experience in combining irinotecan (Camptosar, CPT-11) with taxanes on a weekly schedule in dose-finding and efficacy studies. When chemotherapy is delivered for 4 consecutive weeks followed by a 2-week rest, hematologic toxicity is dose limiting and most prominent during weeks 3 and 4. Dose intensification is feasible if the schedule is modified so the chemotherapy is given on days 1 and 8, with cycles repeated every 3 weeks. The most common nonhematologic toxicities remain asthenia, neuropathy, and diarrhea. Future studies will explore and better define the role of these drug combinations in the treatment of lung cancer.
authors.affiliation: Yale Cancer Center, New Haven, Connecticut, USA. john.murren@yale.edu
authors.forename: J R
authors.initials: JR
authors.lastname: Murren
authors.forename: K
authors.initials: K
authors.lastname: Blum
authors.forename: M
authors.initials: M
authors.lastname: Gallipoli
authors.forename: A
authors.initials: A
authors.lastname: McKeon
authors.forename: R
authors.initials: R
authors.lastname: Rich
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D043823:Taxoids
chemical_list: D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin