title: Split-course versus continuous thoracic radiation therapy for limited-stage small-cell lung cancer: final report of a randomized phase III trial.
abstract: The optimal integration of radiation and chemotherapy for limited-stage small-cell lung cancer (SCLC) remains unclear. This phase III trial was conducted to determine whether chemotherapy plus interdigitating split-course thoracic radiation therapy (RT) improved survival compared with standard-dose continuous thoracic RT. One hundred fourteen patients were randomized to receive 50 Gy thoracic RT delivered in 2.0-Gy fractions given continuously (5 weeks) concurrent with the first 2 cycles of chemotherapy (arm A) or 50 Gy delivered via an interdigitating split course in 2.5-Gy fractions (8 weeks) concurrent with the first 3 cycles of chemotherapy (arm B). During the split-course RT, once-daily radiation was delivered on days 8-17 of each of the first two 21-day cycles and days 8-11 of the third 21-day cycle. All patients received the following chemotherapy: cisplatin/etoposide on cycles 1, 2, and 5 and cyclophosphamide/vincristine/doxorubicin on cycles 3, 4, and 6. Prophylactic cranial irradiation was recommended after a complete response to all therapy. One hundred ten eligible patients were randomized. Grade 3/4 esophagitis was reported in 9% of patients receiving continuous thoracic RT versus 4% of patients receiving split-course RT. Grade 3/4 hematologic toxicity was common in both treatment arms. Complete/partial response was observed in 80% of patients on arm A versus 84% on arm B. Overall survival rates at 5 years were 18% and 17% for arms A and B, respectively. Interdigitating split-course thoracic RT delivered in 2.5-Gy fractions was tolerable in patients with limited-stage SCLC but did not provide a survival advantage.
authors.affiliation: Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. ablackst@wfubmc.edu
authors.forename: A William
authors.initials: AW
authors.lastname: Blackstock
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Bogart
authors.forename: Charles
authors.initials: C
authors.lastname: Matthews
authors.forename: James F
authors.initials: JF
authors.lastname: Lovato
authors.forename: Thomas
authors.initials: T
authors.lastname: McCoy
authors.forename: Kim
authors.initials: K
authors.lastname: Livengood
authors.forename: Coty
authors.initials: C
authors.lastname: Ho
authors.forename: Douglas
authors.initials: D
authors.lastname: White
authors.forename: James N
authors.initials: JN
authors.lastname: Atkins
authors.forename: Antonius A
authors.initials: AA
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin