Multicenter randomized Phase II study of paclitaxel (1-hour infusion), fluorouracil, hydroxyurea, and concomitant twice daily radiation with or without erythropoietin for advanced head and neck cancer.
OBJECTIVE
To expand on our experience with the combination of paclitaxel, fluorouracil, hydroxyurea, and twice daily irradiation (T-FHX) and to assess the impact of weekly administration of erythropoietin (r-HuEpo) on transfusion requirements, we conducted a Phase II multi-institutional trial with a simplified 1-h paclitaxel infusion schedule and randomized patients to receive weekly doses of r-HuEpo.


METHODS
A total of 90 patients with locally advanced head and neck cancers (stage IV, 96%; N(2)/N(3), 66%) were treated on a regimen of 1-h infusion of paclitaxel (100 mg/m(2)/day, day 1), 120-h infusion of 5-fluorouracil (600 mg/m(2)/day, days 0-5); hydroxyurea 500 mg p.o. every 12 h for 11 doses; and radiation 150cGy bid, days 1-5 of each 14-day cycle repeated for five cycles over 10 weeks (7200-7500 cGy). Before initiating therapy, patients were randomized to receive r-HuEpo 40,000 IU s.c. once weekly.


RESULTS
At median follow-up of 40 months, 3-year progression-free survival is 62%, locoregional control is 84%, and systemic control is 79%. Overall survival is 59%. Anemia, leucopenia, dermatitis, and mucositis were the most frequent grade 3 or 4 toxicities. Patients randomized to erythropoietin experienced less grade 2/3 anemia (52 versus 77%; P = 0.02), but transfusion requirements were not significantly different.


CONCLUSIONS
T-FHX is an active and tolerable regimen inducing local tumor control and promising survival with organ preservation in high-risk patients. One h infusion of paclitaxel simplified the regimen without compromising efficacy. Addition of erythropoietin does not reduce the need for transfusion with this nonplatinum-containing regimen. T-FHX should be advanced to a randomized trial and compared with a cisplatin-based concomitant regimen.
Rosen
Fred R
FR
Department of Medicine, Section of Hematology/Oncology, University of Illinois at Chicago, 60637, USA.
Haraf
Daniel J
DJ
Kies
Merrill S
MS
Stenson
Kerstin
K
Portugal
Louis
L
List
Marcy A
MA
Brockstein
Bruce E
BE
Mittal
Bharat B
BB
Rademaker
Alfred W
AW
Witt
Mary Ellyn
ME
Pelzer
Harold
H
Weichselbaum
Ralph R
RR
Vokes
Everett E
EE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage; 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; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011994:Recombinant Proteins; D015996:Survival Rate; D016896:Treatment Outcome
D011994:Recombinant Proteins; D004921:Erythropoietin; D017239:Paclitaxel; D005472:Fluorouracil; D006918:Hydroxyurea