Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer.

Stage III non-small-cell lung cancer (NSCLC) represents a large patient population, accounting for approximately 30% of all NSCLC patients (van Meerbeeck, 2001). This stage has been intensively investigated for the last 10 years. Several studies and meta-analyses have documented an improvement in patients with stage III disease treated with chemotherapy followed by thoracic radiation therapy, compared with radiation therapy alone (Marino et al, 1995; Dillman et al, 1996; Sause et al, 2000). Full-dose cisplatin-based chemotherapy with concurrent thoracic radiation therapy produced encouraging results with relatively severe toxicities (Lee et al, 1996; Reboul et al, 1996; Segawa et al, 2000). Furthermore, results of a randomised trial demonstrated that concurrent administration of cisplatin-based chemotherapy and radiation significantly improved response rate and median survival compared with sequential administration (Furuse et al, 1999); this finding is being confirmed by the Radiation Therapy Oncology Group (RTOG) 9410 trial (Curran et al, 2000). Recently, several new agents with potent activity in the treatment of NSCLC have become available. The use of combination chemotherapy including these new drugs has improved the survival of patients with advanced NSCLC (Giaccone et al, 1998). The feasibilities obtained with concomitant chemoradiotherapy regimens that include new agents are being reported (Greco et al, 1996; Mauer et al, 1998). Cisplatin causes a synergistic effect when given simultaneously with radiation both ex vivo and in vivo (Alvarez et al, 1978; Dewit, 1987). Docetaxel also shows a potential radiosensitising effect both ex vivo and in vivo (Mason et al, 1997; Creane et al, 1999). The combination of docetaxel and cisplatin shows additive effects in lung cancer cell lines (Aoe et al, 1999), and the antitumour spectrums of cisplatin and docetaxel on various lung cancer cell lines are completely different (Matsushita et al, 1999). In clinical trials, the docetaxel/cisplatin combination is one of the most active treatments of advanced NSCLC (Rodriguez et al, 2001). Moreover, patients with relapsed NSCLC treated with single-agent docetaxel had prolonged survival, even after receiving cisplatin-based chemotherapy previously (Shepherd et al, 2000). Studies demonstrated that a weekly administration schedule of docetaxel resulted in markedly reduced myelosuppression compared with every 3-week administration (Tomiak et al, 1994; Hainsworth et al, 1998). Since the weekly schedule may improve therapeutic outcome by increasing the dose intensity of docetaxel while reducing bone marrow toxicity from concurrent radiation therapy, the divided schedule of docetaxel on days on 1, 8, 29, and 36 was also considered to have the same advantage. Based on these concepts, this phase I/II study was conducted to evaluate the safety, toxicity, antitumour activity, and survival effects of chemotherapy consisting of docetaxel plus cisplatin given on days 1, 8, 29, and 36 and concurrent thoracic radiation therapy in patients with locally advanced NSCLC. We planned to administer both cisplatin and docetaxel in as high doses and as early as possible to pursue both local control and eradication of distant micrometastasis.