Effect of rhGM-CSF on haematopoietic reconstitution after chemotherapy in small-cell lung cancer.

In three consecutive pilot studies the effect of recombinant human granulocyte/macrophage-colony-stimulating factor (rhGM-CSF) on haematopoetic recovery after chemotherapy in patients with small-cell lung cancer was investigated. In study I, 20 patients received AIO chemotherapy (A, Adriamycin 25 mg/m2 on days 1 + 2; I, ifosfamide 2 g/m2 on days 1-5; O, vincristine 2 mg on day 1) at 4-week intervals either with or without rhGM-CSF (250 micrograms/m2 sc) from day 8 until recovery of leucocytes. Neither the degree nor the duration of myelosuppression was markedly influenced by rhGM-CSF. Suggesting that these disappointing results were caused by the late onset of GM-CSF application, in the following study we shortened chemotherapy to 3 days and started with GM-CSF on day 4. The main objective of this study was to test whether the earlier administration of GM-CSF allowed treatment intervals to be reduced or the dose to be escalated. After 10 patients had received a starting dose of AIO (A, 50 mg/m2 on day 1; I, 2 g/m2 on days 1-3; 0,2 mg on day 1) alternating with cisplatin (90 mg/m2 on day 1) and etoposide (150 mg/m2 on days 1-3), the dose of ifosfamide and etoposide was escalated to 2.5 g/m2 on days 1-3 and 200 mg/m2 on days 1-3 in the next 10 patients. Treatment was given at 2-week intervals when leucocytes were greater than 3500/mm3 and thrombocytes were greater than 100,000 mm3 on day 14. At each dose level patients were randomized to receive either rhGM-CSF 250 micrograms/m2 s.c. on days 4-12 or no GM-CSF. In this study, rhGM-CSF markedly shortened the duration of leukopenia. Reinstitution of chemotherapy on day 15 was possible at dose level 1 in 1/4 patients without and in 3/4 patients with GM-CSF, and at dose level 2 in 0/5 patients without and in 5/5 patients with GM-CSF. However, the degree of myelosuppression was not improved by GM-CSF. In a third study we tried to apply rhGM-CSF simultaneously with chemotherapy. After 3 patients had received GM-CSF starting on day 1 concurrent to AIO chemotherapy, we noticed an increase of myelosuppression with prolonged neutropenia and thrombocytopenia and stopped this investigation. Considering all patients included in these three consecutive pilot studies, there is no difference in response rates and survival between patients with and without rhGM-CSF treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

RCT Entities:   Population Interventions Outcomes