High-dose chemotherapy with stem cell reinfusion and growth factor support for solid tumors.
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.
de Vries
E G
EG
Department of Internal Medicine, University Hospital, Groningen, The Netherlands.
de Graaf
H
H
Boonstra
A
A
van der Graaf
W T
WT
Mulder
N H
NH
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006133:Growth Substances / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy*; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D006133:Growth Substances