Post-operative sequential high-dose chemotherapy with haematopoietic stem cell support as front-line treatment in advanced ovarian cancer: a phase II multicentre study

Abstract

In spite of multimodal management including aggressive surgery and chemotherapy, the prognosis of advanced ovarian cancer (AOC) remains poor. Multicycle high-dose chemotherapy (HDC) with haematopoietic stem cell (HSC) support has been shown to be a promising procedure in various cancers including AOC. We conducted a phase II multicentre study to evaluate feasibility, toxicity and efficacy of post-operative front-line sequential HDC with HSC support in AOC. Thirty four patients with stage IIIC/IV received a post-operative sequential combination of high-dose cyclophosphamide/epirubicin (D1, D21) with HSC harvesting, high-dose carboplatin (D42, D98) followed by HSC infusion, and dose-dense paclitaxel (D63, D77, D119, D133). Rh-G-CSF (filgrastim) was administered following all cycles. Primary endpoint was pathological complete response rate (pCR). Thirty patients received at least 7 of the scheduled 8 cycles. Haematological toxicity was significant but manageable. Grade 3/4 extra-haematopoietic toxicities were relatively uncommon and reversible. No toxicity-related death was observed. The observed pCR was 37% and did not reach the initial endpoint. Post-operative front-line sequential HDC in AOC is feasible and safe in a multicentre setting. The observed pCR does not support a clear advantage over conventional treatment. This approach remains an experimental strategy to further optimise and validate.

Are there candidates for high-dose chemotherapy in ovarian carcinoma?

“…These results were observed when HDC was used either as front-line treatment [19,27], or as consolidation therapy [17,28-32]. However published randomized phase III trials did not confirm these results.…”

Solid tumors in adults

“…1 An ABMTR retrospective analysis of 421 patients with relapsed ovarian cancer who received high-dose chemotherapy and autologous stem cell rescue from 1989 through 1996 reported similar results. 6 In conclusion, HDC with autologous stem cell support has largely failed to prove any benefi cial role in the treatment of advanced ovarian cancer. Patients who underwent transplantation who had good performance status and platinum-sensitive tumors had better EFS and OS rates of 22% and 55%, respectively.…”