title: 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.
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France. goncalvesa@marseille.fnclcc.fr
authors.forename: A
authors.initials: A
authors.lastname: Gonçalves
authors.forename: R
authors.initials: R
authors.lastname: Delva
authors.forename: M
authors.initials: M
authors.lastname: Fabbro
authors.forename: L
authors.initials: L
authors.lastname: Gladieff
authors.forename: J-P
authors.initials: JP
authors.lastname: Lotz
authors.forename: J-M
authors.initials: JM
authors.lastname: Ferrero
authors.forename: C
authors.initials: C
authors.lastname: Linassier
authors.forename: P-H
authors.initials: PH
authors.lastname: Cottu
authors.forename: P
authors.initials: P
authors.lastname: Viens
authors.forename: J-M
authors.initials: JM
authors.lastname: Extra
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000601:surgery* / Q000628:therapy*; D011182:Postoperative Care; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome