Titre du document / Document title

Sequential cycles of high-dose chemotherapy with dose escalation of carboplatin with or without paclitaxel supported by G-CSF mobilized peripheral blood progenitor cells: a phase I/II study in advanced ovarian cancer

Auteur(s) / Author(s)

WANDT H. ⁽¹⁾ ; BIRKMANN J. ⁽¹⁾ ; DENZEL T. ⁽¹⁾ ; SCHÄFER K. ⁽¹⁾ ; SCHWAB G. ⁽²⁾ ; PILZ D. ⁽²⁾ ; EGGER H. ⁽³⁾ ; BOTH A. ⁽³⁾ ; GALLMEIER W. M. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Klinikum Nürnberg, Bone Marrow Transplantation Unit, Medical Department 5, Institute of Medical Oncology and Hematology, München, ALLEMAGNE
⁽²⁾ Amgen Inc, München, ALLEMAGNE
⁽³⁾ Klinikum Neumarkt, Department of Obstetrics and Gynecology, University Erlangen-Nürnberg, München, ALLEMAGNE

Résumé / Abstract

To assess high-dose carboplatin chemotherapy with or without paclitaxel with filgrastim mobilized peripheral blood progenitor cell (PBPC) support in a phase I/II study, a total of 21 patients with mostly chemonaive disease received four cycles of high-dose chemotherapy. Cycle 1 (cyclophosphamide, 6 g/m²) was followed by two cycles of carboplatin (1600 mg/m² or 1800 mg/m²). Cycle 4 consisted of carboplatin (1600 mg/m²), etoposide (1600 mg/m²), and melphalan (140 mg/m²). Further chemotherapy intensification was achieved by adding paclitaxel (175 mg/m²) to all cycles with a fixed carboplatin dose (1600 mg/m²). Ototoxicity was dose-limiting for escalation of sequential cycles of carboplatin. Grade 2 and grade 3 ototoxicity, hearing loss not requiring a hearing aid, or hearing loss correctable with a hearing aid, was observed with carboplatin at 1800 mg/m². The maximum tolerated dose (MTD) of sequential carboplatin, therefore, was identified in this study as 1600 mg/m². After cycles 1, 2, 3 and 4 the median duration of leukopenia (<1.0 x 10⁹/1) was 7, 4, 4 and 6 days. Severe grade 3 and 4 infections were seen in only 7% of cycles. Of the 21 patients evaluable for disease response, 57% had complete remissions and 43% experienced partial remissions resulting in an overall response rate of 100%. The median progression-free survival is 25 (15-36) months, the median overall survial 36.5 (15-38) months. Most patients were suboptimally debulked or had bulky residual disease at the start of chemotherapy. Sequential high-dose chemotherapy to a maximum dose of 1600 mg/m² carboplatin is effective and feasible. A randomized, prospective trial comparing sequential high-dose chemotherapy with optimal standard chemotherapy is now warranted.

Revue / Journal Title

Bone marrow transplantation   ISSN 0268-3369   CODEN BMTRE9 

Source / Source

1999, vol. 23, n^o8, pp. 763-770 (45 ref.)

Langue / Language

Anglais

Editeur / Publisher

Nature Publishing Group , Basingstoke, ROYAUME-UNI  (1986) (Revue)

Mots-clés anglais / English Keywords

Malignant tumor ; Ovary ; Advanced stage ; Chemotherapy ; Treatment ; High dose ; Antineoplastic agent ; Toxicity ; Limit dose ; Carboplatin ; Hematopoietic cell ; Stem cell ; Autograft ; Blood ; Combined treatment ; Human ; Platinum II Complexes ; Female genital diseases ; Ovarian diseases ; Graft ;

Mots-clés français / French Keywords

Tumeur maligne ; Ovaire ; Stade avancé ; Chimiothérapie ; Traitement ; Dose forte ; Anticancéreux ; Toxicité ; Dose limite ; Carboplatine ; Cellule hématopoïétique ; Cellule souche ; Autogreffe ; Sang ; Traitement associé ; Homme ; Platine II Complexe ; Appareil génital femelle pathologie ; Ovaire pathologie ; Greffe ;

Mots-clés espagnols / Spanish Keywords

Tumor maligno ; Ovario ; Estadio avanzado ; Quimioterapia ; Tratamiento ; Dosis fuerte ; Anticanceroso ; Toxicidad ; Dosis límite ; Carboplatino ; Célula hematopoyética ; Célula primitiva ; Autoinjerto ; Sangre ; Tratamiento asociado ; Hombre ; Platino II Complejo ; Aparato genital hembra patología ; Ovario patología ; Injerto ;

Localisation / Location

INIST-CNRS, Cote INIST : 21176, 35400008427586.0030