Induction chemotherapy and concurrent chemoradiotherapy for locoregionally advanced head and neck cancer: a multi-institutional phase II trial investigating three radiotherapy dose levels.
BACKGROUND
We hypothesized induction chemotherapy (IndCT) would improve distant control (DC) without compromising locoregional control (LRC) for locoregionally advanced head and neck cancer patients. Additionally, we systematically lowered radiotherapy (RT) doses attempting to maintain LRC while decreasing toxicity.


METHODS
Stages III-IV (M0) locoregionally advanced head and neck cancer patients received carboplatin/paclitaxel (Taxol) IndCT followed by four or five cycles consisting of 5 days of paclitaxel, fluorouracil, hydroxyurea, and BID RT followed by a nine day break. RT dose to gross disease (high risk), intermediate, and low-risk volumes were reduced from cohort A (n = 68): 75, 60, and 45 Gy; to cohort B (n = 64): 75, 54, and 39 Gy; then cohort C (n = 90): 72, 51, and 36 Gy.


RESULTS
A total of 222 patients accrued from November 1998 to September 2002. Median follow-up is 56 months. In all, 93/96/76% achieved a complete response to concurrent chemoradiotherapy (CRT) in cohort A/B/C. Three- and 5-year overall survivals (OSs) are 68% and 62%, respectively. Five-year LRC and DC are 91% and 87%, respectively. Response to IndCT predicted for OS, LRC, and time to progression (TTP). Cohort C patients had similar OS (P = 0.95), LRC, and DC, but worse (TTP) (P = 0.027).


CONCLUSIONS
IndCT before CRT reduces distant progression while maintaining high LRC. The cohort B schedule provides the best therapeutic ratio. A randomized trial investigating IndCT before CRT has been initiated.
Salama
J K
JK
Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA.
Stenson
K M
KM
Kistner
E O
EO
Mittal
B B
BB
Argiris
A
A
Witt
M E
ME
Rosen
F
F
Brockstein
B E
BE
Cohen
E E W
EE
Haraf
D J
DJ
Vokes
E E
EE
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction
D016190:Carboplatin; D017239:Paclitaxel; D005472:Fluorouracil; D006918:Hydroxyurea