title: A phase I and pharmacological study of amrubicin and topotecan in patients of small-cell lung cancer with relapsed or extensive-disease small-cell lung cancer.
abstract: Cisplatin-based chemotherapy is considered to be a standard treatment in patients with relapsed or extensive-disease (ED) small-cell lung cancer (SCLC), the survival benefit remains modest. Relapsed or ED-SCLC patients were enrolled. Topotecan and amrubicin were administered on Days 1-5 and on Days 3-5, respectively. Nine patients received a total of 24 cycles. Since all three patients experienced dose-limiting toxicity (grade 4 neutropenia lasting for more than 4 days, grade 3 febrile neutropenia, and grade 4 thrombocytopenia) at the third dose level (topotecan: 0.75 mg/m2, amrubicin 40 mg/m2), the maximum tolerated dose was determined to be this dose level. Objective response was observed in six patients (67%). The maximum concentration (Cmax) and area under the plasma concentration-time curve (AUC) of amrubicin increased in a dose-dependent manner. Amrubicin did not influence the pharmacokinetics of topotecan. The Cmax and AUC of amrubicin were correlated with the duration of grade 4 neutropenia. The mean Cmax of topotecan on day 2 in responders (22.9+/-3.6) was significantly higher than that in non-responders (10.9+/-0.4). This phase I study showed the safety and activity of two-drug combination of amrubicin and topotecan in patients with relapsed or ED-SCLC.
authors.affiliation: Department of Respiratory Medicine, NHO Minami-Okayama Medical Center, 4066 Hayashima, Hayashima-cho, Tsukubo-gun, Okayama 701-0304, Japan. shibayamat@s-okayama.hosp.go.jp
authors.forename: Takuo
authors.initials: T
authors.lastname: Shibayama
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Tada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueoka
authors.forename: Shingo
authors.initials: S
authors.lastname: Harita
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Segawa
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Nogami
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kuyama
authors.forename: Tetsu
authors.initials: T
authors.lastname: Shinkai
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D015415:Biomarkers; D019772:Topotecan; C055866:amrubicin