DOSE-INTENSE THERAPY WITH ETOPOSIDE, IFOSFAMIDE, CISPLATIN, AND EPIRUBICIN (VIP-E) IN 107 CONSECUTIVE PATIENTS WITH, LIMITED-STAGE AND EXTENSIVE-STAGE NON-SMALL-CELL LUNG-CANCER

Background: We conducted a phase I/II trial to assess the feasibility and activity of combination chemotherapy with etoposide, ifosfamide, c isplatin, and epirubicin in limited-stage (LS, stage I-IIIB) and exten sive-stage (ES, stage IV) non-small-cell lung cancer (NSCLC). End-poin ts were treatment-related morbidity and mortality, response rate, dura tion of response, and survival. Patients and methods: Chemotherapy fol lowed by granulocyte colony-stimulating factor was given at a dose of etoposide (500 mg/m(2)), ifosfamide (4000 mg/m(2)), cisplatin (50 mg/m (2)), and epirubicin (50 mg/m(2)) (VIP-E) to 107 patients with NSCLC. Twenty-five patients with qualifying responses proceeded to high-dose chemotherapy with autologous peripheral blood stem cell transplantatio n after etoposide (1500 mg/m(2)), ifosfamide (12,000 mg/m(2)), carbopl atin (750 mg/m(2)) and epirubicin (150 mg/m(2)) (VIC-E) conditioning. Results of conventional-dose VIP-E: 35 of 102 (34%) evaluable patients responded (2 CR's, 33 PR's), 33/102 patients (33%) showed no change ( NC); the remainder of patients progressed with therapy (PD). Objective response rate was 68% (4% CR, 64% PR) in LS-NSCLC and 23% (1.4% CR, 2 1.4% PR) in ES-NSCLC. Median duration of survival was 13 months in LS- NSCLC and 5.5 months in ES-NSCLC. Two-year survival was 26% in LS and 2% in ES-NSCLC. Results of high-dose VIC-E: 23 of 24 evaluable patient s improved or maintained prior responses (92%), 1 patient showed NC. T reatment mortality was 4%. Median duration of survival was 17 months i n LS-NSCLC and 10 months in ES-NSCLC. Two-year survival was 30% in LS and 8% in ES-NSCLC. Conclusion: Response-rates and survival after conv entional-dose VIP-E chemotherapy are comparable to other published tri als of combination chemotherapy in NSCLC. Toxicity and mortality is ac ceptable in limited stage, but unacceptably high in extensive stage NS CLC. Although better response-rates were achieved in the high-dose arm , they did not translate into improved survival. Most stage IV NSCLC-p atients will neither benefit from VIP-E conventional dose, nor from VI C-E high dose chemotherapy. Whether selected LS-patients with partial or complete responses to VIP-E induction chemotherapy could benefit fr om dose intensification in an adjuvant or neo-adjuvant setting remains to be determined.