The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck

Purpose: 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 combin ation of carboplatin (CBDCA), paclitaxel, and once-daily radiation for pati ents with locally advanced disease, Additionally, the pharmacokinetics of p aclitaxel were investigated. Methods and Materials: 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 adva nced disease; 77% had T4 disease and 21% had T3 disease, Fifty-eight percen t had N2b-N3 disease. Results: Sixty patients were evaluable for response and survival with a med ian follow-up of 30 months (range 7-70), Ninety-eight percent of patients c ompleted prescribed therapy. One patient died after refusing medical manage ment 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 fo r the entire cohort is 33 months. Response to therapy and status of the nec k at presentation were the only prognostic factors found to influence survi val. 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 defi nitive once-daily external beam radiation therapy is well tolerated with ov er 90% of patients completing prescribed therapy. An ultimate CR rate of gr eater than 70% was obtained, which translated directly into improved surviv al. 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 pro gnosis. (C) 2000 Elsevier Science Inc.