title: A phase I study of combination S-1 plus cisplatin chemotherapy with concurrent thoracic radiation for locally advanced non-small cell lung cancer.
abstract: A combination of S-1, a newly developed oral 5-fluorouracil derivative, and cisplatin is reported to show anti-tumour activity against advanced non-small cell lung cancer (NSCLC). Because S-1 shows synergistic effects with radiation, we conducted a phase I study to evaluate the maximum tolerated doses (MTDs), recommended doses (RDs), and dose-limiting toxicities (DLTs) of cisplatin and S-1 when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) in patients with locally advanced NSCLC. Chemotherapy consisted of two 4-week cycles of cisplatin administered on days 1 and 8, and S-1 administered on days 1-14. S-1/cisplatin dosages (mg/m(2)/day) were escalated as follows: 60/30, 60/40, 70/40, 80/40 and 80/50. Twenty-two previously untreated patients were enrolled. The MTDs and RDs for S-1/cisplatin were 80/50 and 80/40, respectively. DLTs included febrile neutropaenia, thrombocytopaenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced radiation pneumonitis>grade 2 and only one patient experienced grade 3 radiation oesophagitis. The overall response rate was 86.4% with a median survival time of 24.4 months. These results indicate that combination cisplatin-S-1 chemotherapy with concurrent thoracic radiation would be a feasible treatment option and a phase II study is currently under way.
authors.affiliation: Department of Medicine, National Hospital Organization, Sanyo Hospital, Ube, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Chikamori
authors.forename: Daizo
authors.initials: D
authors.lastname: Kishino
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Nogami
authors.forename: Haruhito
authors.initials: H
authors.lastname: Kamei
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kuyama
authors.forename: Kenichi
authors.initials: K
authors.lastname: Gemba
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takemoto
authors.forename: Susumu
authors.initials: S
authors.lastname: Kanazawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueoka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Segawa
authors.forename: Saburo
authors.initials: S
authors.lastname: Takata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin