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Phase III Comparative Study of High-Dose Cisplatin Versus a Combination of Paclitaxel and Cisplatin in Patients With Advanced Non–Small-Cell Lung Cancer

From the Grosshansdorf Hospital, Grosshansdorf; Zentralkrankenhaus Gauting, Gauting, Germany; Meir Hospital, Kfar Saba, Israel; Academisch Ziekenhuis Maastricht, Maastricht, the Netherlands; Helsinki University Hospital, Helsinki, Finland; Ospedale Carlo Forlanini, Rome, Italy; Guy’s Hospital, London, United Kingdom; Centre Hospitalier Universitaire de Brest, Brest, France; Centro Riferimento Oncologico, Aviano, Italy; Bristol-Myers Squibb Pharmaceutical Research Institute, Waterloo, Belgium.

Address reprint requests to Ulrich Gatzemeier, MD, Department of Thoracic Oncology, Krankenhaus Grosshansdorf, Wohrendamm 80, Grosshansdorf, 22927, Germany; email pneumo.onko{at}t-online.de

PURPOSE: New effective chemotherapy is needed to improve the outcome of patients with advanced non–small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC.

PATIENTS AND METHODS: Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m²) or a combination of paclitaxel (175 mg/m², 3-hour infusion) and cisplatin (80 mg/m²) every 21 days.

RESULTS: Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P = .028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P = .026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P = .862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms.

CONCLUSION: This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.

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