Phase II clinical trial of parenteral hydroxyurea and hyper-fractionated, accelerated external beam radiation therapy in patients with advanced squamous cell carcinoma of the head and neck: toxicity and efficacy with continuous ribonucleoside reductase inhibition.
BACKGROUND
Almost all concurrent chemoradiation regimens for head and neck are platinum based; however, cisplatin is associated with severe renal, oto-, and neurotoxicity. Hydroxyurea (HU) has been associated with fewer irreversible toxicities. We obtained HU in parenteral form to be administered continually during the radiation treatment. Intravenous HU promised better pharmacokinetics and cell cycle blockade.


METHODS
Participants had biopsy-proven, untreated squamous cell carcinoma of the oral cavity, oropharynx (stage IV) and hypopharynx (stages II-IV). Radiation therapy consisted initially of 74.4 Gy administered in twice daily 1.2-Gy fractions. After 20 patients, the radiation dose was reduced to 60.0 Gy, and another 16 patients were enrolled.


RESULTS
Patients received HU by Continuous Ambulatory Drug Delivery (CADD) pump on a daily x5 schedule during radiation therapy. Because of persistent long-term dysphagia, after 20 patients, the dose of external beam radiation therapy was reduced from 74 to 60 Gy, and the duration of concurrent HU was correspondingly reduced. The new regimen was much better tolerated. The median survival for the group as a whole was 30 months. Within this small study, there were no significant differences in survival, regional control, or local control between the 2 groups.


CONCLUSIONS
Lower doses of concurrent parenteral HU and hyper-fractionated radiation therapy are tolerable and promising.
Beitler
Jonathan J
JJ
Department of Radiation Oncology, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, New York, USA. jbeitler92@alumni.gsb.columbia.edu
Smith
Richard V
RV
Owen
Randall P
RP
Silver
Carl E
CE
Mazumdar
Madhu
M
Wadler
Scott
S
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D007260:Infusion Pumps; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D006918:Hydroxyurea