title: Low-dose fractionated radiation as a chemopotentiator of neoadjuvant paclitaxel and carboplatin for locally advanced squamous cell carcinoma of the head and neck: results of a new treatment paradigm.
abstract: OBJECTIVE
  Current therapies for locally advanced squamous cell carcinoma of the head and neck (SCCHN) result in 50% long-term remission. Low-dose radiotherapy (<100 cGy) induces enhanced cell killing in vitro via the hyper-radiation sensitivity phenomenon but has not been used in the clinical setting. On the basis of the demonstrated synergy between chemotherapy and low-dose fractionated RT, a novel neoadjuvant therapy was designed using low-dose fractionated RT as a chemopotentiator for locally advanced SCCHN.
  
  
  METHODS
  Forty patients with locally advanced SCCHN received paclitaxel (225 mg/m2), carboplatin (area under the curve of 6), and four 80-cGy fractions of radiotherapy (two each on Days 1 and 2). This sequence was repeated on Days 22 and 23.
  
  
  RESULTS
  Of the 40 patients enrolled, 39 were assessable. Grade 3 or worse toxicities included neutropenia (50%), infection (13%), arthralgias/myalgias (3%), skin (8%), lung (3%), and allergic reaction (3%), with no Grade 5 toxicity. The response was assessed radiographically and by panendoscopy. At the primary site, 11 patients (28%) had a complete response, 24 (62%) had a partial response, and 4 (10%) had stable disease. Of those with lymph node involvement, 10 (31%) had a complete response, 12 (38%) a partial response, 9 (28%) had stable disease, and 1 (3%) had progressive disease. The overall response rate was 82%.
  
  
  CONCLUSIONS
  Low-dose fractionated RT combined with paclitaxel and carboplatin is effective in SCCHN and has a similar toxicity profile to chemotherapy alone. This novel approach provided a response rate of 90% at the primary site and a nodal response rate of 69%. Additional scientific investigation of this new treatment paradigm is warranted.
authors.affiliation: Department of Medicine, University of Kentucky Markey Cancer Center, Lexington 40536, USA. smarno0@pop.uky.edu
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Arnold
authors.forename: William F
authors.initials: WF
authors.lastname: Regine
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Ahmed
authors.forename: Joseph
authors.initials: J
authors.lastname: Valentino
authors.forename: Paul
authors.initials: P
authors.lastname: Spring
authors.forename: Mahesh
authors.initials: M
authors.lastname: Kudrimoti
authors.forename: Daniel
authors.initials: D
authors.lastname: Kenady
authors.forename: Philip
authors.initials: P
authors.lastname: Desimone
authors.forename: Mohammed
authors.initials: M
authors.lastname: Mohiuddin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D016896:Treatment Outcome
chemical_list: D016190:Carboplatin; D017239:Paclitaxel