A Phase I/II trial of concurrent docetaxel and radiation after induction chemotherapy in patients with poor prognosis squamous cell carcinoma of the head and neck

Abstract

BACKGROUNDThe authors conducted a Phase I/II study in patients with a poor prognosis who had locally advanced squamous cell carcinoma of the head and neck (SCCHN) and who were treated initially with induction chemotherapy. Patients were treated with weekly docetaxel and concurrent daily fractionated radiation therapy to determine the maximum tolerated dose (MTD) of docetaxel and the efficacy of the regimen.METHODSTwenty‐two patients were enrolled, and 21 patients were treated. Eight patients had Stage III SCCHN, and 13 patients had Stage IV SCCHN without distant metastases and were treated first with 2‐3 cycles of induction chemotherapy, which consisted of cisplatin plus 5‐fluorouracil with or without leucovorin. Patients with a poor prognosis were identified as those who achieved a partial response to induction treatment, achieved a complete response with a positive biopsy, or were at high risk for developing recurrent disease. Patients were treated subsequently with concurrent, escalating doses of docetaxel (given weekly × 6) and once daily 200‐centigray radiation fractions.RESULTSThree patients were treated with a weekly docetaxel dose of 20 mg/m2 without dose‐limiting toxicity (DLT). Both patients who were treated at the next dose level of 30 mg/m2 experienced DLT. A dose of 25 mg/m2 was studied without DLT in the 16 patients who were treated, establishing this as the MTD. Sixty‐seven percent of the patients are alive without disease at a median follow‐up of 35 months (range, 12–59 months) after the initiation of chemoradiotherapy.CONCLUSIONSThe MTD of weekly docetaxel with concurrent daily radiation therapy in the postinduction setting was 25 mg/m2. Disease free survival data from this study were good and indicated that this regimen was effective in the treatment of patients with SCCHN who had a poor prognosis. Cancer 2002;95:1472–81. © 2002 American Cancer Society.DOI 10.1002/cncr.10873

Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck

“…These incidences of haematologic toxicities were significantly different from previous studies using 5-FU-containing regimens, where the incidence of grade 3 or 4 leukopenia was 29 -81% (Vokes et al, 2000;Adelstein et al, 2003). Recently, taxanes, such as paclitaxel and docetaxel, which exhibit activity against SCCHN, are being increasingly used for concurrent chemoradiotherapy to improve the treatment outcome (Kies et al, 2001;Tishler et al, 2002;Katori et al, 2004). Kies et al (2001) reported that concomitant infusional paclitaxel and fluorouracil, oral hydroxyurea, and radiation therapy achieved a clinical CR rate of 69%, 3-year locoregional control rate of 86%, and 3-year overall survival rate of 60% in patients with locally advanced SCCHN.…”

Phase I and initial phase II results from a trial investigating weekly docetaxel and carboplatin given neoadjuvantly and then concurrently with concomitant boost radiotherapy for locally advanced squamous cell carcinoma of the head and neck

“…Recent Phase I/II data have demonstrated the feasibility and potential efficacy of concurrent radiotherapy and docetaxelbased chemotherapy. Tishler et al 9 showed that a weekly dose of 25 mg/m 2 docetaxel and once-daily radiotherapy is safe and can provide potentially encouraging DFS in patients with cisplatinum-resistant advanced disease. Likewise, Katori et al 10 confirmed the feasibility of docetaxel 60 mg/m 2 , cisplatin 70 mg/ m 2 , and 5-day continuous infusion 5-fluorouracil (5-FU) 600 mg/m 2 per day given in 2 cycles over 4 weeks during a course of once-daily radiotherapy.…”

“…This type of chronic toxicity was not unexpected and was, in fact, less frequent than that reported by other groups. 9,13 We selected carboplatin over cisplatin for the current trial to improve the likelihood of patient tolerance to treatment, while still providing a similar mechanism of action for tumor sensitization to docetaxel and radiotherapy. Although more clinically established than carboplatin, cisplatin is nephrotoxic and requires intensive i.v.…”

Docetaxel induction therapy in locally advanced squamous cell carcinoma of the head and neck

“…The activity of docetaxel in SCCHN, coupled with the drug's in vitro radiosensitizing properties (Creane et al, 1999;Mason et al, 1999;Pradier et al, 2001), provide the basis for clinical trials with docetaxel as a component of concurrent or alternating chemoradiation in locally advanced SCCHN (Koukourakis et al, 1999;Hesse et al, 2000;Tishler et al, 2002). Docetaxel-based chemoradiation regimens have been shown to be feasible and active as induction and adjuvant therapy.…”

“…Docetaxel-based chemoradiation regimens have been shown to be feasible and active as induction and adjuvant therapy. The phase I/II study by Tishler et al (2002) considered daily radiation concurrent with weekly docetaxel in 21 patients with stage III -IV SCCHN, who responded poorly to induction chemotherapy, and demonstrated an ORR of 86% (CR 57%). Radiation was delivered at 2 Gy day À1 , to a total dose of 66 -74 Gy.…”