title: Alternating doublets: establishing the optimal multifractionated dosing schedule to administer docetaxel, cisplatin, gemcitabine, and vinorelbine in combination.
abstract: The purpose was to determine the optimal multifractionated (MF) dosing schedule to permit the delivery of four active agents in nonsmall cell lung cancer simultaneously in alternating doublets (docetaxel-cisplatin alternating with gemcitabine-vinorelbine). Three MF schedules were used: schedule A weekly; schedule B twice weekly for 2 weeks repeated every 21 days; and schedule C twice weekly every other week. Dose fractions were fixed for each component drug: docetaxel 50 mg/m2 plus cisplatin 20 mg/m2 and gemcitabine 500 mg/m2 plus vinorelbine 25 mg/m2. GCSF 480 micrograms was administered as a single dose concomitant with chemotherapy if the WBC was between 1500 and 3500 cells/mm3. Hematological toxicity, particularly leukopenia and anemia, was the predominant adverse effect observed and was demonstrated on all three schedules. Schedule B was not feasible in that none of the seven cycles were completed and six of seven required hospitalization for febrile neutropenia. The delivery of a four-drug combination chemotherapy regimen consisting of docetaxel, cisplatin, gemcitabine, and vinorelbine is feasible with an alternating doublet multifractionated dosing scheme with either a weekly or twice weekly every other week schedule.
authors.affiliation: Cancer Center of Boston, 125 Parker Hill Ave., Boston, Plymouth, MA 02120-2847, USA. jlokich@cancercenter.com
authors.forename: Jacob
authors.initials: J
authors.lastname: Lokich
authors.forename: Norwood
authors.initials: N
authors.lastname: Anderson
authors.forename: Frank
authors.initials: F
authors.lastname: Coco
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever; D006801:Humans; D007262:Infusions, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine