THE LIMITS OF CHEMOTHERAPY DOSE INTENSIFICATION USING GRANULOCYTE-COLONY-STIMULATING FACTOR ALONE IN EXTENSIVE SMALL-CELL LUNG-CANCER

Human Recombinant Granulocyte Colony Stimulating Factor (G-CSF) allows rapid neutrophil recovery after chemotherapy-induced leukopenia. In a prospective series of 54 patients with extensive small cell lung canc er, we evaluated the feasibility and efficacy of accelerated delivery of the AVI chemotherapy regimen. Treatment consisted of Doxorubicin 50 mg/m(2) day 1, Etoposide 120 mg/m(2) day 1-3 and Ifosfamide 2 g/m(2) (+ Mesna 4 g) day 1 and 2 given every 2 weeks and followed by G-CSF (N eupogen(R), Amgen Roche 5 mu g/kg/day s.c, day 4-14). Twenty-seven (50 %) patients could nor receive the total of six courses: seven because of severe septic complication, 10 because of Grade 4 thrombopenia, sev en because of non-response and three because of patient refusal. Chemo therapy had to be delayed in 58 out of the 244 administered courses an d this was due to thrombopenia in 48% of cases. The probability of opt imal dose-on-time administration was 64% at three courses. The mean ac tually received dose intensity was 93% at six courses (27 patients tre ated). It was increased by 76% compared to our previously published co nventional 3-week interval chemotherapy. The median neutrophil nadirs were stable during the successive treatment courses while haemoglobin and platelet values significantly worsened from cycle 1 to cycle 6. Th e overall response rate after three courses was 77% in the 48 evaluabl e patients. The median survival is 8 months overall and 5 months disea se free. The actuarial survival is 22% at 2 years. We conclude that su bstantial dose intensification with accelerated chemotherapy and G-CSF support is feasible. However, the rate of severe infectious episodes is too high and thrombopenia is the main limiting factor. Either growt h factors active on the megacaryocytic lineage or haematological rescu e with peripheral blood stem cells might be useful in this setting.