title: Concurrent hyperfractionated irradiation and chemotherapy for unresectable nonsmall cell lung cancer. Results of Radiation Therapy Oncology Group 90-15.
abstract: BACKGROUND
  Clinical trials of hyperfractionated radiation therapy and induction chemotherapy followed by standard radiation therapy have shown improved survival in patients with unresectable nonsmall cell lung cancer (NSCLC). Radiosensitization may improve local tumor control when chemotherapy is given concurrently with hyperfractionated radiation therapy, but also may increase toxicity. A Phase I/II trial, Radiation Therapy Oncology Group 90-15, was designed to evaluate whether this strategy could improve survival with acceptable toxicity and be part of a Phase III trial of chemoradiation sequencing.
  
  
  METHODS
  Vinblastine (5 mg/M2 weekly x 5 weeks) and cisplatin (75 mg/M2 days 1, 29, and 50) were given during twice-daily irradiation (1.2 Gy, 6 hours apart) to 69.6 Gy in 58 fractions in 6 weeks. Eligible patients had American Joint Committee on Cancer (AJCC) Stage II (unresected) or IIIA-B NSCLC and Karnofsky performance status 70 or greater; there were no weight loss restrictions.
  
  
  RESULTS
  Of 42 eligible patients, 76% had greater than 5% weight loss, 45% had T4 primary tumors, and 62% were Stage IIIB. All protocol treatment was completed in 53%. Acute toxicity was predominantly hematologic with 19 of 42 (45%) having Grade 4 toxicity or higher, three (7%) with septic death. Ten of 42 (24%) had Grade 3 or higher esophagitis. There were two (4.7%) patients with Grade 3 or higher (1 lung and 1 esophagus) and two (4.7%) with Grade 4 or higher (1 lung and 1 hematologic) late toxicities. Median survival time was 12.2 months, with an overall 1-year survival of 54%, an estimated 2 year survival of 28% and a 1-year progression free survival of 38%.
  
  
  CONCLUSIONS
  For patients with unresectable nonsmall cell lung cancer, who were not selected on the basis of weight loss, concurrent hyperfractionated irradiation and chemotherapy had more intense acute toxicity than hyperfractionation alone, but late toxicity was acceptable. One and 2-year survival rates were 54 and 28%, respectively.
authors.affiliation: Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Byhardt
authors.forename: C B
authors.initials: CB
authors.lastname: Scott
authors.forename: D S
authors.initials: DS
authors.lastname: Ettinger
authors.forename: W J
authors.initials: WJ
authors.lastname: Curran
authors.forename: R L
authors.initials: RL
authors.lastname: Doggett
authors.forename: C
authors.initials: C
authors.lastname: Coughlin
authors.forename: C
authors.initials: C
authors.lastname: Scarantino
authors.forename: M
authors.initials: M
authors.lastname: Rotman
authors.forename: B
authors.initials: B
authors.lastname: Emami
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D004941:Esophagitis / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects; D015431:Weight Loss
chemical_list: D014747:Vinblastine; D002945:Cisplatin