Summary
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 μg/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 > 3500/mm3 and thrombocytes were > 100 000 mm3 on day 14. At each dose level patients were randomized to receive either rhGM-CSF 250 μg/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 GMCSF. 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. Optimal scheduled rhGM-CSF application shortens the period of myelosuppression and allows reinstitution of chemotherapy at 2-week intervals. Whether these modifications are able to improve the overall treatment results, has to be determined in future clinical trials.
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Abbreviations
- rhGM-CSF:
-
recombinant human granulocyte/macrophage-colony-stimulating factor
- AIO:
-
Adriamycin/ifosfamide/vineristine
References
Bronchud MH, Scarffe JH, Thatcher N et al (1987) Phase I/II study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer. Br J Cancer 56:809–813
Crawford J, Ozer H, Johnson D(for the G-CSF study group) (1990) Granulocyte colony-stimulating factor: prevention of chemotherapy induced febrile neutropenia (FN) in patients with small cell lung cancer (SCLC). A randomized double blind placebo controlled trial (abstract). Proc ASCO 9:229
Gabrilove JL, Jakubowski A, Scher HS et al. (1988) Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium. N Engl J Med 24:1414–1422
Luikart SD, MacDonald M, Herzan D et al. (1990) Phase I trial of etoposide (VP-16), carboplatin (CBDCA) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for extensive small cell lung cancer (SCLC) (abstract). Proc ASCO 9:236
Morstyn G, Campbell L, Lieschke G et al. (1989) Treatment of chemotherapy-induced neutropenia by subcutaneously administered granulocyte colony-stimulating factor with optimization of dose and duration of therapy. J Clin Oncol 10:1554–1562
Morstyn G, Stuart-Harris R, Bishop J et al. (1989) Optimal scheduling of granulocyte macrophage colony-stimulating factor (GMCSF) for the abrogation of chemotherapy induced neutropenia in small cell lung cancer (SCLC) (abstract). Proc ASCO 8:219
Neidhardt J, Mangalik A, Kohler W et al. (1989) Granulocyte colony-stimulating factor stimulates recovery of granulocytes in patients receiving dose-intensive chemotherapy without bone marrow transplantation. J Clin Oncol 11:1685–1692
Schiller JH, Storer B, Oken MM et al. (1990) Randomized trial of granulocyte macrophage colony-stimulating factor in patients with small cell carcinoma of the lung (abstract). Proc ASCO 9:244
Takada M, Fukuoka M, Furuse K et al. (1990) Recombinant human G-CSF (rG-CSF) in patients with combination chemotherapy (CT) of mitomycin, vindesine, and cisplatin (MVP) (abstract). Proc ASCO 9:224
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Havemann, K., Klausmann, M., Wolf, M. et al. Effect of rhGM-CSF on haematopoietic reconstitution after chemotherapy in small-cell lung cancer. J Cancer Res Clin Oncol 117 (Suppl 4), S203–S207 (1991). https://doi.org/10.1007/BF01613228
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DOI: https://doi.org/10.1007/BF01613228