A targeted supradose cisplatin chemoradiation protocol for advanced head and neck cancer.
BACKGROUND
Hypothesizing that cisplatin (DDP) drug resistance is dose dependent and the radiosensitizing effect of DDP is clinically beneficial, we conducted a chemoradiation protocol using extremely high doses of DDP delivered intra-arterially (IA) to locally advanced head and neck tumors.


METHODS
Twenty-nine patients with untreated stage IV disease received 4 weekly infusions of 150 mg/m2, simultaneous systemic DDP neutralization with intravenous (IV) bolus sodium thiosulfate, and concomitant radiotherapy (180 to 200 cGy/day x 35 fractions).


RESULTS
The complete response rate of the 24 evaluable patients as determined with repeat biopsies was 23/24 (96%). Of the 29 patients evaluable for toxicity, central nervous system complications related to the infusion technique occurred with 2/110 infusions, both of which were reversible. The rate of grade III to IV chemotoxicity was 13%. The median length of follow-up was 22 months. There have been 6 recurrences: 1 local; 3 regional; and 2 at distant sites. The projected overall and disease-free 3-year survival was 88% and 53%, respectively.


CONCLUSIONS
We conclude that the combination of rapid selective delivery of supradose DDP/IV thiosulfate neutralization and concomitant radiotherapy can be safely and effectively applied to patients with advanced head and neck cancer. Preliminary survival analysis indicates that this approach may improve the prognosis for patients with an otherwise devastating disease.
Robbins
K T
KT
Department of Otolaryngology/Head and Neck Surgery, University of Tennessee, Memphis 38163.
Vicario
D
D
Seagren
S
S
Weisman
R
R
Pellitteri
P
P
Kerber
C
C
Orloff
L
L
Los
G
G
Howell
S B
SB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D002614:Chelating Agents; D002945:Cisplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011879:Radiotherapy Dosage; D015996:Survival Rate; D013885:Thiosulfates
D002614:Chelating Agents; D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin