Double-cycle high-dose chemotherapy with peripheral blood stem cells and hematopoietic growth factor support in patients with advanced solid tumor. A pilot study by the Hong Kong Biotherapy Group.

BACKGROUND

High-dose chemotherapy with autologous bone marrow transplantation has been useful in some patients with advanced breast, lymphoma, or germ cell tumors. Double-cycle high-dose chemotherapy may be able to deliver an even higher total dose within a given time period. It is important to determine whether peripheral blood stem cells and hematopoietic growth factors can diminish the hematopoietic toxicity of such a treatment.

METHODS

From November 1989 to May 1991, 14 patients were enrolled in two cycles of high-dose chemotherapy consisting of cyclophosphamide, 4.5 g/m2; cisplatin, 150 mg/m2; and etoposide, 900 mg/m2 in each cycle. The first five patients received peripheral blood stem cells harvested from 8-10 leukaphereses during steady state. The next nine patients, besides receiving peripheral blood stem cells mobilized by growth factors, also received either granulocyte-macrophage colony-stimulating factor (GM-CSF) at 250 micrograms/m2/day by two subcutaneous (s.c.) injections given 12 hours apart from day 6 until neutrophil recovery or granulocyte colony-stimulating factor (G-CSF) at 200 micrograms/m2 as daily s.c. injections.

RESULTS

For the first five patients, there was a median of 14 days from the first day of absolute marrow suppression to neutrophil count exceeding 500/microliters and a median of 15 days for a platelet count exceeding 20,000/microliters. For the next nine patients, with the use of either G-CSF or GM-CSF, there was a median of 8 days for a neutrophil count exceeding 500/microliters and and a median of 11 days for a platelet count exceeding 20,000/microliters.

CONCLUSION

With the use of peripheral stem cells and growth factors, high-dose chemotherapy could be given safely every 30 days with acceptable toxicity. A high complete response rate was seen in patients with nasopharyngeal carcinoma and in patients with small cell and non-small cell lung cancer who either had not received previous chemotherapy or who had responded to previous chemotherapy.