Flexible granulocyte colony-stimulating factor dosing in ovarian cancer patients who receive dose-intense taxol therapy.
As has been reported with other chemotherapeutic agents, evidence is emerging to suggest that increased taxol dose intensity is associated with improved therapeutic efficacy. Granulocyte colony-stimulating factor (G-CSF) effectively protects the bone marrow from taxol-induced neutropenia and allows for higher taxol dose administration. This report addresses the optimal use of G-CSF as a supportive agent for dose-intense taxol therapy. Forty-seven patients were evaluated. Each ovarian cancer patient received taxol with G-CSF support, with starting doses of 250 mg/m2 per 21 days and 10 micrograms/kg/d, respectively. Five patients were treated with the same dose of G-CSF for multiple cycles. Forty-two patients were given "flexible" G-CSF dosing. Instead of reducing taxol dose after a cycle of therapy complicated by febrile neutropenia (F+N+), the G-CSF dose was increased. Only after a second episode of F+N+ was the taxol dose reduced. The initial 5 patients who developed F+N+ after taxol (250 mg/m2) and G-CSF (10 micrograms/kg/d) were retreated at the same doses of both drugs; subsequently, 4 of 5 patients had another episode of F+N+. With flexible G-CSF dosing, taxol dose intensity could be maintained at the target level in 34 of 42 patients (81% of the cohort). Sixteen of these patients (38% of the cohort) would have required taxol dose reductions for F+N+ if flexible G-CSF dosing had not been used. By increasing the G-CSF dose when indicated, patients at high risk for recurrence of F+N+, because they had already experienced one episode, appeared to have a lower risk of developing a recurrent episode. These data suggest that flexible G-CSF dosing may have merit and may allow the administration of more dose-intense taxol. A prospective, randomized, controlled clinical trial of flexible G-CSF dosing versus fixed-dose G-CSF appears warranted.
Link
C J
CJ
Medical Ovarian Cancer Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Bicher
A
A
Kohn
E C
EC
Christian
M C
MC
Davis
P A
PA
Adamo
D O
DO
Reed
E
E
Sarosy
G A
GA
D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D009503:Neutropenia / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage*
D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel