Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer.
BACKGROUND
Induction chemotherapy with cisplatin plus fluorouracil followed by radiotherapy is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer. The value of adding chemotherapy to radiotherapy and the optimal timing of chemotherapy are unknown.


METHODS
We randomly assigned patients with locally advanced cancer of the larynx to one of three treatments: induction cisplatin plus fluorouracil followed by radiotherapy, radiotherapy with concurrent administration of cisplatin, or radiotherapy alone. The primary end point was preservation of the larynx.


RESULTS
A total of 547 patients were randomly assigned to one of the three study groups. The median follow-up period was 3.8 years. At two years, the proportion of patients who had an intact larynx after radiotherapy with concurrent cisplatin (88 percent) differed significantly from the proportions in the groups given induction chemotherapy followed by radiotherapy (75 percent, P=0.005) or radiotherapy alone (70 percent, P<0.001). The rate of locoregional control was also significantly better with radiotherapy and concurrent cisplatin (78 percent, vs. 61 percent with induction cisplatin plus fluorouracil followed by radiotherapy and 56 percent with radiotherapy alone). Both of the chemotherapy-based regimens suppressed distant metastases and resulted in better disease-free survival than radiotherapy alone. However, overall survival rates were similar in all three groups. The rate of high-grade toxic effects was greater with the chemotherapy-based regimens (81 percent with induction cisplatin plus fluorouracil followed by radiotherapy and 82 percent with radiotherapy with concurrent cisplatin, vs. 61 percent with radiotherapy alone). The mucosal toxicity of concurrent radiotherapy and cisplatin was nearly twice as frequent as the mucosal toxicity of the other two treatments during radiotherapy.


CONCLUSIONS
In patients with laryngeal cancer, radiotherapy with concurrent administration of cisplatin is superior to induction chemotherapy followed by radiotherapy or radiotherapy alone for laryngeal preservation and locoregional control.
Forastiere
Arlene A
AA
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231-1000, USA. af@jhmi.edu
Goepfert
Helmuth
H
Maor
Moshe
M
Pajak
Thomas F
TF
Weber
Randal
R
Morrison
William
W
Glisson
Bonnie
B
Trotti
Andy
A
Ridge
John A
JA
Chao
Clifford
C
Peters
Glen
G
Lee
Ding-Jen
DJ
Leaf
Andrea
A
Ensley
John
J
Cooper
Jay
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D003679:Deglutition; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009367:Neoplasm Staging; D011878:Radiotherapy / Q000009:adverse effects; D013060:Speech; D016019:Survival Analysis; D017211:Treatment Failure
D002945:Cisplatin; D005472:Fluorouracil