With the help of stem cell reinfusion and hematopoietic
growth factors, it is possible to get up to a ten-fold dose increase for certain chemotherapeutic drugs. A number of reasons may have made high-dose
chemotherapy less dangerous and therefore more acceptable in a more upfront treatment setting. One of these is the addition of peripheral stem cell harvest obtained after mobilization with a hematopoietic
growth factor alone or after
chemotherapy followed by a hematopoietic
growth factor, which seems to result in a faster recovery of neutrophils and platelets compared to bone marrow reinfusion alone. The combination of various hematopoietic
growth factors could potentially improve hematopoietic recovery of the high-dose
chemotherapy regimen. The relevance of
tumor cells sometimes present in the reinfused hematopoietic stem cells is as yet unknown. High-dose
chemotherapy may be interesting for a number of solid
tumors such as nonseminomatous testicular
carcinoma, breast carcinoma in the metastatic and adjuvant setting, ovarian
carcinoma,
tumors of young adults such as
Ewing sarcoma and
small cell lung carcinoma. In patients with refractory nonseminomatous
testicular cancer there have been a number of studies performed with high-dose
chemotherapy showing a 15% complete and prolonged remission. For other
tumor types and settings it will be necessary to perform randomized studies before firm conclusions can be drawn. For example, this is especially important for patients with
breast carcinoma with more than three positive axillary lymph nodes. Preliminary data from various groups compared to historical controls treated with standard
adjuvant chemotherapy show favorable results of
adjuvant chemotherapy containing high-dose
chemotherapy. Many relatively small nonrandomized studies are performed in various stages of disease for ovarian
carcinoma. Although there are long-term survivors reported it is currently difficult to draw firm conclusions. The potentially safer
therapy of high-dose
chemotherapy may reveal in the near future the role of high-dose
chemotherapy in solid
tumors.