Oncologia Medica, Azienda Ospedaliera S.Croce e Carle, Via Michele Coppino 26, 12100 Cuneo, Italy (E-mail:gnumico@libero.it)
Second-line chemotherapy does not have a proven impact on survival or on quality of life in head and neck cancer patients. Furthermore, responses are rare and usually of brief duration. Similar figures are also reported for second-line treatment of non-small-cell lung cancer; response rates rarely exceed 10% and median survival is 4 months. However, two recent randomized trials suggested a survival benefit when docetaxel, administered as a single agent, was compared with best supportive care [1] or to another drug (ifosfamide or vinorelbine) [2], although the response rates obtained in the experimental arms were 5.8% and 6.7%, respectively.
We planned a phase II trial in order to asses objective activity and toxicity of docetaxel administered as a single agent, at a dose of 80 mg/m2 every 21 days, in patients with squamous-cell head and neck cancer, relapsed after treatment with a platinum-based regimen. An optimal two-stage design was used in order to calculate the sample size. For an error of 0.05 and a ß error of 0.20, a p1 (the target activity level) of 25% and a p0 (the lowest level of activity that is of interest) of 5%, 17 evaluable patients had to be enrolled and at least two responses out of 17 patients should have been found in order to reject the null hypothesis.
Inclusion criteria were the following: histologically proven squamous-cell carcinoma of the head and neck; local relapse or metastatic disease not suitable of further loco-regional treatment; leucocytes >3000/ml; platelets >100 000/ml; normal renal, hepatic and cardiac function; no concomitant serious medical condition.
Patients were staged and periodically evaluated with computed tomography (CT) scan of the head and neck region, nasal endoscopy and chest X-ray. Before treatment patients underwent a clinical examination in which performance status was assessed and active symptoms were recorded. Docetaxel 80 mg/m2 was administered over 60 min after a pre-medication consisting of prednisolone 50 mg, 12 and 1 h before treatment, and 12, 24, 36, 48 and 60 h after treatment. Intravenous infusion of metoclopramide 40 mg and dexametasone 8 mg was planned as anti-emetic prophylaxis.
From July 1998 to July 2000, 18 patients were enrolled at our institution. Disease- and treatment-related patient characteristics are reported in Table 1. All but one patient was pre-treated with at least three courses of full-dose (75100 mg/m2) cisplatin-based chemotherapy. The patient not pre-treated with cisplatin was a 75-year-old woman with peformance status (PS) 2, who was pre-treated with carboplatin and fluorouracil. Four patients were pre-treated with a regimen consisting of cisplatin, paclitaxel and fluorouracil.
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Among the 16 patients with symptoms at the beginning of the treatment, seven (44%) reported at least a partial relief at some time during treatment: six of the 13 patients with pain (46%) and two of the five patients with dysphagia (40%).
The response rate was assessed using an intent-to-treat method: all patients were considered in the analysis, although in three the imaging evaluation was not performed due to early death. A confirmed partial response was recorded in two patients [response rate 11%; 95% confidence interval (CI) 0% to 25%], six patients had stable disease, and seven patients were considered in progression during treatment. After a median follow up of 14 months, 17 patients died. Median time-to-progression was 19 weeks. Median survival was 26 weeks. One-year survival calculated according to the KaplanMeyer method was 20%.
Docetaxel is an active agent in squamous-cell head and neck cancer. Studies assessing single-agent docetaxel, administered at 100 mg/m2 as 1 h infusion every 34 weeks to chemotherapy-naive patients with recurrent loco-regional or metastatic disease, showed response rates of 2742% [3]. However, no study assessing the use of single-agent docetaxel in second-line treatment has been published to our knowledge. In combination with vinorelbine, a response rate of 44% has been reported among 27 patients; however, the rate of grade 3/4 neutropenia was 100% [4]. Our group has previously reported a 23% response rate using a combination of carboplatin and fluorouracil in patients responding to a previous first-line, cisplatin-based treatment [5]. In contrast, a non-platinum-based chemotherapy did not show activity in a similar patient population [6].
The patient population enrolled in the present study had poor prognostic features: heavy chemotherapy pre-treatment (some patients with paclitaxel, some patients with progressive disease during treatment) and poor base-line PS [median Eastern Cooperative Oncology Group (ECOG) PS 2]. The response rate obtained (11%) confirms the activity of docetaxel in this disease. Notably, as was clearly assessed through randomized trials in non-small-cell lung cancer, this study also suggests that a relatively low response rate translates into a high rate of symptomatic improvement (almost 50%). We conclude that testing active agents such as docetaxel also in relapsed/metastatic head and neck cancer is worthwhile: further studies should be conducted in order to confirm the benefit in terms of quality of life.
G. Numico & M. Merlano
Oncologia Medica, Azienda Ospedaliera S.Croce e Carle, Via Michele Coppino 26, 12100 Cuneo, Italy (E-mail:gnumico@libero.it)
References
1.
Shepherd FA, Dancey J, Ramlau R et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000; 18: 20952103.
2.
Fossella FV, DeVore R, Kerr RN et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum containing chemotherapy regimens. J Clin Oncol 2000; 18: 23542362.
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