title: Alternating chemotherapy and radiotherapy for limited-stage intermediate and high-grade non-Hodgkin's lymphomas: long-term results for 96 patients with tumors > 5 cm.
abstract: BACKGROUND
  The role and timing of radiotherapy for optimal treatment of localized aggressive non-Hodgkin's lymphoma (NHL) is controversial. We report the long-term results of a single-institution pilot study of alternating chemotherapy (CT) and radiotherapy (RT) in patients with clinical stages I or II tumors exceeding 5 cm.
  
  
  METHODS
  From 1981 to 1992, 96 patients with stages I-II aggressive NHL received an alternating regimen of CT and RT consisting of 8 cycles of CT with 3 courses of RT interjected after the 2nd, 3rd and 4th cycles of CT. The CT combined cyclophosphamide, doxorubicin, teniposide and prednisone every 28 days. Each RT course was started 8 to 10 days after CT (15 Gy in 6 fractions to initially involved and contiguous areas).
  
  
  RESULTS
  The median age was 54 years. The disease predominantly located in the head and neck area was stage II in 63% of patients. Bulky tumors (10 cm or larger) were found in 24% of patients. Six patients discontinued CT because of acute toxicity (mucositis). The mean relative dose intensity achieved for doxorubicin, cyclophosphamide and teniposide were 72%, 82%, and 78%, respectively. Late toxicity consisted mostly of severe xerostomia lasting more than 2 years in 7 patients irradiated in Waldeyer's ring. The complete response (CR) rate was 91%; 20 of the 86 patients in CR relapsed (3 locally only). The median follow-up was 61 months, and at 5 years, overall survival (OS) was 77%. Classification according to the International Prognostic Factor Index was possible for 54 patients, all but three of whom were in the 'low risk' group (0-1 factor). Bulky disease was the only unfavorable prognostic factor (P < 0.001) for CR, freedom from progression (FFP) and OS rates; the low relative dose intensity of CT achieved in this study did not affect outcome.
  
  
  CONCLUSIONS
  Alternating chemo-radiotherapy for localized aggressive NHL was feasible and yielded long-term results comparable to those obtained with standard treatments, despite a reduction in dose intensity considerably below that of CHOP which suggested synergistic effects of CT and RT in this scheme.
authors.affiliation: Institut Gustave-Roussy, Villejuif, France.
authors.forename: J N
authors.initials: JN
authors.lastname: Munck
authors.forename: F
authors.initials: F
authors.lastname: Dhermain
authors.forename: S
authors.initials: S
authors.lastname: Koscielny
authors.forename: T
authors.initials: T
authors.lastname: Girinsky
authors.forename: P
authors.initials: P
authors.lastname: Carde
authors.forename: J
authors.initials: J
authors.lastname: Bosq
authors.forename: D
authors.initials: D
authors.lastname: Decaudin
authors.forename: M
authors.initials: M
authors.lastname: Juliéron
authors.forename: J M
authors.initials: JM
authors.lastname: Cosset
authors.forename: M
authors.initials: M
authors.lastname: Hayat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000209:etiology; D010349:Patient Compliance; D010865:Pilot Projects; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects; D013713:Teniposide / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D013713:Teniposide; D011241:Prednisone