Phase II study of sequential treatment of advanced non-small-cell lung cancer: three cycles of high-dose epirubicin plus cisplatin followed by weekly vinorelbine.

Previous phase I, II, and III studies on high-dose epirubicin (HDEPI), alone or in combination with cisplatin (CP), indicate an interesting activity of this drug in the treatment of non–small-cell lung cancer (NSCLC). However, the toxicological profile of HDEPI limits its prolonged use. In our experience, vinorelbine (VNR) seems to be a suitable drug for long-term monotherapy for advanced NSCLC. On these grounds, advanced NSCLC patients were treated with the following strategy: 3 consecutive cycles of CP 60 mg/m2 and HDEPI 120 mg/m2 on day 1, every 3 weeks; then, irrespective of response, weekly VNR at a dose of 25 mg/m2 was administered at home. From December 1996 to March 1998, 25 patients entered the study. After receiving 3 cycles of CP/HDEPI, 8 patients (32%) had a partial response and 3 (12%) had a minor response. Nine patients had stable disease (36%) and 4 (16%) had progressive disease. Twenty-three patients received weekly VNR, and the median number of administrations was 10 (range, 1-38). After VNR treatment, we observed a partial response in 2 patients who previously had stable disease. Therefore, the overall response rate to sequential treatment was 40%; median time to progression was 7 months (range, 2-26 months). The major toxicities due to the CP/HDEPI regimen were neutropenia (72%) and alopecia (80%). During the VNR treatment, grade 3/4 neutropenia was seen in 36% of patients. The doses and the timing of VNR administrations were modified according to toxicity. Symptoms such as cough, dyspnea, and pain, present in 21 patients before the treatment, improved in 11 cases (52%). Median overall survival is 9 months (range, 3-40+ months); one patient is still alive after 40 months. One- and 2-year survival rates are, respectively, 44% and 16%. This study confirms the activity of CP/HDEPI in NSCLC and indicates that the sequential treatment of CP/HDEPI for 3 cycles followed by weekly VNR could be considered an effective strategy for locally advanced or metastatic NSCLC.