Concurrent paclitaxel and radiation in the treatment of locally advanced head and neck cancer.
OBJECTIVE
To determine the feasibility of an organ preservation regimen consisting of infusional paclitaxel administered concurrently with radiotherapy to patients with locally advanced head and neck squamous cell carcinoma (HNSCC).


METHODS
Thirty-three previously untreated patients with stage III or IV tumors were enrolled onto the study. Paclitaxel was administered as a 120-hour continuous infusion every 3 weeks during the course of radiation therapy. Sixteen patients received a paclitaxel dose of 105 mg/m(2), and 17 patients received 120 mg/m(2). Radiation was delivered in a standard format at 1.8 Gy/d to a total dose of 70.2 to 72 Gy.


RESULTS
Three months after therapy, a 76% complete response (CR) at the primary site and a 70% overall CR was achieved. At 36 months, locoregional control was 55.7%, overall survival was 57.8%, and disease-free survival was 51.1%. The median survival duration for all 33 patients was greater than 50 months at the time of this report. Local toxicities including mucositis, dysphagia, and skin reactions were severe but tolerable. All patients retained functional speech, and all but four patients were swallowing food 3 months after treatment. Steady-state plasma concentrations for paclitaxel were not achieved during a 120-hour infusion, suggesting a nonlinear process. Tumor volume quantified by pretreatment computerized tomography imaging was associated with likelihood of response and survival.


CONCLUSIONS
Paclitaxel administered as a 120-hour continuous infusion in combination with radiotherapy is a feasible and promising treatment for patients with advanced HNSCC.
Sunwoo
J B
JB
Head and Neck Surgery Branch, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
Herscher
L L
LL
Kroog
G S
GS
Thomas
G R
GR
Ondrey
F G
FG
Duffey
D C
DC
Solomon
B I
BI
Boss
C
C
Albert
P S
PS
McCullugh
L
L
Rudy
S
S
Muir
C
C
Zhai
S
S
Figg
W D
WD
Cook
J A
JA
Mitchell
J B
JB
Van Waes
C
C
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D003679:Deglutition / Q000187:drug effects / Q000528:radiation effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010865:Pilot Projects; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013060:Speech / Q000187:drug effects / Q000528:radiation effects; D015996:Survival Rate
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel