Lessons learned from a decade of clinical trials of high-dose chemotherapy in ovarian cancer

Abstract

Ovarian cancer is one of the most chemosensitive solid tumors and therefore a good example to explore high-dose chemotherapy (HDC). Interest in pursuing this treatment arose in the late 1980s following the success of HDC in treating hematological cancers and improvements in supportive care with peripheral blood stem cells. Experience from phase II trials and analysis of Bone Marrow Transplant Registry data led to the launch of several randomized phase III trials in the late 1990 s. Initial enthusiasm for this treatment was in part due to the preliminary positive data emerging from HDC in breast cancer. Five randomized trials of HDC in ovarian cancer have been conducted and all experienced difficulty in recruitment. Their different designs and results are reviewed, as well as some of the lessons that have been learned about HDC in solid tumors in the last decade.

Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015

“…Other solid tumours Data from randomized phase III studies comparing high-dose vs conventional-dose chemotherapy for first-line treatment of advanced ovarian cancer and limited or extensive small cell lung cancer 177,178 have shown no statistically significant difference in PFS or OS. Limitations due to study design, difficulty in recruitment and toxicity may have accounted for the lack of favourable results, that were expected based on previous phase II and retrospective analyses 179 of such highly chemosensitive diseases.…”

Trends in Use of and Survival after Autologous Hematopoietic Cell Transplantation in North America, 1995-2005: Significant Improvement in Survival for Lymphoma and Myeloma during a Period of Increasing Recipient Age

“…Over the past 20 years, the practice of autoHCT has evolved to include a new source of hematopoietic cells (peripheral blood), 1 new diseases/indications for which autoHCT has demonstrated efficacy and improved survival, 2–3 as well as elimination of utilization for some indications such as breast and ovarian cancer for which autoHCT has not been demonstrated to be superior to chemotherapy. 4–6 Improvements in supportive care include anti-microbial agents, improved radiographic testing and the improvement in care that comes from increased experience with autoHCT utilization. Simultaneously, there have been major changes to cancer treatments with the development of monoclonal antibodies (rituximab, alemtuzumab), immunomodulatory drugs (thalidomide, lenalidomide), small molecule inhibitors (bortezomib, sirolimus, temsirolimus, everolimus), hypomethylating agents (azacitidine, decitabine) and other novel therapies.…”

Intraepithelial T cells and tumor proliferation

“…7,10 Chemotherapy intensification and high-dose approaches followed by stem cell support have not yielded any improvement in progressionfree or overall survival. [11][12][13] Thus, aggressive efforts to intensify therapy may increase morbidity, but have not been shown to significantly improve long-term survival over the past 2 decades. 14 It is conceivable that identification of biomarkers that capture intrinsic tumor properties or host factors affecting tumor behavior may help individualize therapy and result in improved therapeutic results and/or reduced toxicity.…”