Weekly carboplatin and paclitaxel followed by concomitant paclitaxel, fluorouracil, and hydroxyurea chemoradiotherapy: curative and organ-preserving therapy for advanced head and neck cancer.
OBJECTIVE
The paclitaxel, fluorouracil, and hydroxyurea regimen of paclitaxel, infusional fluorouracil, hydroxyurea, and twice-daily radiation therapy (TFHX) administered every other week has resulted in 3-year survival rates of 60% of stage IV patients. Locoregional and distant failure rates were 13% and 23%, respectively. To reduce distant failure rates, we added a brief course of induction chemotherapy to TFHX.


METHODS
Sixty-nine patients received six weekly doses of carboplatin (AUC2) and paclitaxel (135 mg/m2) followed by five cycles of TFHX.


RESULTS
Ninety-six percent had stage IV disease. Response to induction chemotherapy was partial response 52% and complete response (CR) 35%. Symptomatically, there was a significant reduction in mouth and throat pain. The most common grade 3 or 4 toxicity was neutropenia (36%). Best response following completion of TFHX was CR in 83%. Toxicities of TFHX consisted of grade 3 or 4 mucositis (74% and 2%) and dermatitis (47% and 14%). At a median follow-up of 28 months, locoregional or systemic disease progression were each noted in five patients. The overall 3-year progression-free survival was 80% (95% confidence interval [CI], 71% to 90%), and the 2- and 3-year overall survival rates were 77% (95% CI, 66% to 87%) and 70% (95% CI, 59% to 82%), respectively. At 12 months, five patients were completely feeding-tube dependent.


CONCLUSIONS
Administration of carboplatin and paclitaxel before TFHX chemoradiotherapy results in high response activity and may decrease distant failure rates. Overall survival, progression, and organ preservation/functional outcome data support definitive evaluation of this approach.
Vokes
Everett E
EE
Department of Medicine, Section of Hematology/Oncology, University of Chicago. IL 60637-1470, USA. evokes@medicine.bsd.uchicago.edu
Stenson
Kerstin
K
Rosen
Fred R
FR
Kies
Merrill S
MS
Rademaker
Alfred W
AW
Witt
Mary Ellyn
ME
Brockstein
Bruce E
BE
List
Marcy A
MA
Fung
Bing Bing
BB
Portugal
Louis
L
Mittal
Bharat B
BB
Pelzer
Harold
H
Weichselbaum
Ralph R
RR
Haraf
Daniel J
DJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011788:Quality of Life; D011879:Radiotherapy Dosage; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
D016190:Carboplatin; D017239:Paclitaxel; D005472:Fluorouracil; D006918:Hydroxyurea