title: The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck.
abstract: OBJECTIVE
  Unresectable squamous cell carcinomas of the head and neck (SCCHN) continue to pose a significant therapeutic challenge. This report defines the toxicities, efficacy, and prognostic factors associated with the combination of carboplatin (CBDCA), paclitaxel, and once-daily radiation for patients with locally advanced disease. Additionally, the pharmacokinetics of paclitaxel were investigated.
  
  
  METHODS
  From 1993-1998, 62 patients with Stage III-IV SCCHN were treated with 70.2 Gy of RT at 1.8 Gy/fraction/day to the primary site. Weekly chemotherapy was given during RT consisting of paclitaxel (45 mg/m(2)/wk) and CBDCA (100 mg/m(2)/wk). All patients presented with locally advanced disease; 77% had T4 disease and 21% had T3 disease. Fifty-eight percent had N2b-N3 disease.
  
  
  RESULTS
  Sixty patients were evaluable for response and survival with a median follow-up of 30 months (range 7-70). Ninety-eight percent of patients completed prescribed therapy. One patient died after refusing medical management for pseudomembranous colitis and is scored as a Grade 5 toxicity. Two patients suffered Grade 4 leukopenia. Median number of break days was two. A clinical complete response (CR) at the primary site was obtained in 82%, with a total (primary site and neck) CR rate of 75%. The median survival for the entire cohort is 33 months. Response to therapy and status of the neck at presentation were the only prognostic factors found to influence survival. The median survival for patients who attained a CR is 49 months versus 9 months in those who did not attain a CR (p < 0.0001). The 2- and 3-year overall survival for complete responders are 79% and 61%. Plasma paclitaxel concentrations in the range shown to be radiosensitizing were achieved.
  
  
  CONCLUSIONS
  Weekly carboplatin and paclitaxel given concurrently with definitive once-daily external beam radiation therapy is well tolerated with over 90% of patients completing prescribed therapy. An ultimate CR rate of greater than 70% was obtained, which translated directly into improved survival. With 48% 3-year overall survival for the entire group, this regimen is an excellent option for this group of patients with a historically poor prognosis.
authors.affiliation: Department of Radiation Oncology, Greenebaum Cancer Center, University of Maryland Medical System, Baltimore, MD, USA. msunthar@umaryland.edu
authors.forename: M
authors.initials: M
authors.lastname: Suntharalingam
authors.forename: M L
authors.initials: ML
authors.lastname: Haas
authors.forename: B A
authors.initials: BA
authors.lastname: Conley
authors.forename: M J
authors.initials: MJ
authors.lastname: Egorin
authors.forename: S
authors.initials: S
authors.lastname: Levy
authors.forename: S
authors.initials: S
authors.lastname: Sivasailam
authors.forename: J M
authors.initials: JM
authors.lastname: Herman
authors.forename: M C
authors.initials: MC
authors.lastname: Jacobs
authors.forename: W C
authors.initials: WC
authors.lastname: Gray
authors.forename: R A
authors.initials: RA
authors.lastname: Ord
authors.forename: J A
authors.initials: JA
authors.lastname: Aisner
authors.forename: D A
authors.initials: DA
authors.lastname: Van Echo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D011838:Radiation-Sensitizing Agents; D016190:Carboplatin; D017239:Paclitaxel