Both factors also have hematopoietic roles, and are present in substantial amounts in the bone marrow, supporting the idea that neural and neuroendocrine factors have a direct effect on the bone microenvironment.
In 1997, we reported interesting results in the treatment of advanced gastric cancer with an intensive weekly low dose 5-FU, epidoxorubicin (epiADR), CDDP, 6S-stereoisomer-leucovorin (LV), and bone marrow support with the haemopoietic growth factor filgrastim (Cascinu et al, 1997).
Our expectation of high-dose treatment with bone marrow support has thus far not been fulfilled either in the adjuvant or in the metastatic setting.
We conclude that the method of combined bone marrow support by G-CSF and haematopoietic progenitor cells in autologous whole blood collected before each cycle of a 2-weekly regimen of cisplatin-ifosfamide does not result in clinically measurable reduced bone marrow toxicity compared with what can be expected by the use of G-CSF alone.
In the 1980s, high-dose treatment with bone marrow support was introduced into breast cancer treatment after it had proven successful in more chemosensitive diseases such as leukaemia and lymphoma.
These studies have spanned several radionuclides as well as several mAb, fragments and approaches, including dose intensification with bone marrow support; combined therapy with other modalities (ie, CM-RIT); biodegradable peptide linkers; and pretargeting.
A meta-analysis of 14 studies with higher doses without bone marrow support in metastatic breast cancer showed a survival advantage, although this was modest [ 20].
Autologous marrow transplantation or peripheral blood stem cell reinfusion has been investigated as a means to overcome bone marrow toxicity in RIT, thereby allowing administration of activity doses more than twice as high as without any bone marrow support.
In addition, this mode of delivery of CPA and TTP over four cycles enables to deliver twice as much total dose as a single course of HDCT with bone marrow support (Kennedy et al, 1991).
> Future strategies to improve clinical efficacy of cG250 could be: (1) tumor pretargeting; (2) high dose RIT with bone marrow support or transplant or (3) use of high linear energy transfer (LET) particles emitting radionuclides.
