title: Decreased myelotoxicity of gemcitabine and cisplatin in advanced non-small cell lung cancer (NSCLC) with cisplatin infusion on day 15.
abstract: In a multicenter phase II Italian trial that used a 28-day dosing schedule of gemcitabine on days 1, 8, and 15 and cisplatin on day 2, thrombocytopenia and neutropenia were the main dose-limiting toxicities observed. The aim of the present study was to determine whether using 15-day cisplatin in lieu of the standard 2-day schedule in combination with weekly gemcitabine would decrease expected myelotoxicities, particularly thrombocytopenia. Fifty-one patients with advanced non-small cell lung cancer (NSCLC), a median age of 62 years (range 31-76) and baseline Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1, were enrolled. Twenty-four patients had stage IIIA-B disease and 27 had stage IV. Patients received gemcitabine 1000 mg/m(2) on days 1, 8, 15, and cisplatin 100 mg/m(2) on day-15, every 28 days for a total of 151 cycles. All patients were evaluable for toxicity. Grades 3 and 4 thrombocytopenia was observed in 16% of patients, grades 3 and 4 neutropenia in 35% of patients, and grade 3 anemia in 4% of patients (no grade 4 anemia). Nonhematologic toxicity was mild. Two patients had grade 3 vomiting, and another had grade 4 hepatic toxicity only after gemcitabine administration. The dose intensity of gemcitabine and cisplatin was well maintained. Of the 45 patients evaluable for response, there were 22 (49%) partial responders, 7 (15.5%) minimal responders, 9 (20%) with stable disease, and 7 (15.5%) progressions. Compared with the schedule used in a multicenter phase II Italian trial (day 2 cisplatin), day-15 cisplatin decreases incidences of thrombocytopenia (16 vs. 52%) and anemia (4 vs. 25%); the occurrence of neutropenia is similar (35 vs. 36%). Response rates are also similar (49 vs. 54%).
authors.affiliation: Department of Experimental Medicine and Pathology, Medical Oncology, La Sapienza University, Rome, Italy 00161. enrico.cortesi@uniroma1.it
authors.forename: E
authors.initials: E
authors.lastname: Cortesi
authors.forename: S
authors.initials: S
authors.lastname: Ramponi
authors.forename: M
authors.initials: M
authors.lastname: Corona
authors.forename: L
authors.initials: L
authors.lastname: Moscetti
authors.forename: F
authors.initials: F
authors.lastname: Grifalchi
authors.forename: A
authors.initials: A
authors.lastname: Oliva
authors.forename: A
authors.initials: A
authors.lastname: Lembo
authors.forename: S
authors.initials: S
authors.lastname: Gasperoni
authors.forename: A
authors.initials: A
authors.lastname: Padovani
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced* / Q000517:prevention & control; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D003841:Deoxycytidine / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000517:prevention & control; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000517:prevention & control; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine