Phase 1 trial of combined chemotherapy and reirradiation for recurrent unresectable head and neck cancer.
BACKGROUND
The management of recurrent unresectable head and neck cancer remains a challenging problem. Based on the circadian rhythm concept, we sought to determine the maximum tolerated dose (MTD) of infusional 5-flourouracil (5-FU), hydroxyurea (HU), and reirradiation (RT).


METHODS
Bolus 5-FU was escalated from 300 mg/m(2)/d to a 10-hour infusion beginning at midnight, increased at 150 mg/m(2)/d increments. HU, 1.5 g, remained constant. Chemotherapy was given on weeks 1 and 4. RT was given daily, 2.0 Gy per fraction on weeks 1 and 2 followed by a 1-week break, then hyperfractionated weeks 4 and 5, total dose 50 Gy. The goal was to deliver a continuous course of RT to 60 Gy after the MTD was determined with an additional week of chemotherapy.


RESULTS
Six cohorts were treated to establish the 5-FU MTD of 900 mg/m(2)/d. The seventh cohort received continuous RT and 5-FU, 750 mg/m(2)/d, one dose level below the MTD. Two hematologic, three skin, and six mucosal >or= grade 3 toxicities were noted in 7 of 16 patients. The median survival was 10.2 months and the 1-year survival was 41%. The median survival for the entire group was 9.4 months, with a 1- and 2-year survival of 39% and 15%, respectively.


CONCLUSIONS
RT can be given in a continuous fashion with concurrent 5-FU and HU. Because radiation sensitization should be achievable at nontoxic doses of 5-FU, we recommend 600 mg/m(2)/d in phase a II setting.
Spencer
Sharon
S
University of Alabama at Birmingham, Department of Radiation Oncology, 619 South 19th Street, WTI #119, Birmingham, Alabama 35233, USA. sspencer@uabmc.edu
Wheeler
Richard
R
Peters
Glenn
G
Meredith
Ruby
R
Beenken
Sam
S
Nabel
Lisle
L
Wooten
Ann
A
Soong
Seng-Jaw
SJ
Salter
Merle
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015331:Cohort Studies; D003131:Combined Modality Therapy; 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; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D005472:Fluorouracil; D006918:Hydroxyurea