A phase I trial of dose-dense (biweekly) carboplatin combined with paclitaxel and pegfilgrastim: a feasibility study in patients with untreated Stage III and IV ovarian, tubal or primary peritoneal cancer: a Gynecologic Oncology Group study.
OBJECTIVE
Dose-dense regimens have been shown to improve outcome when given as adjuvant therapy to patients with breast cancer compared with their three weekly counterparts. We investigated the feasibility of a dose-dense regimen with carboplatin/paclitaxel followed by pegfilgrastim in patients with advanced ovarian cancer. We also investigated the toxicities including the percentage of patients with grade 2 or greater peripheral neurotoxicity and the clinical response of this regimen.


METHODS
Women with untreated Stage III or IV epithelial ovarian, (fallopian) tubal, or primary peritoneal cancer were treated with carboplatin area under the curve (AUC) 5 and paclitaxel 175 mg/m(2) day one, and pegfilgrastim 6 mg day two every 2 weeks for six cycles.


RESULTS
Between 9/06 and 9/08, 43 patients enrolled. Thirty-one patients completed six or more cycles of therapy. The dose limiting toxicities resulting in treatment discontinuation included: grade 3 and 4 neuropathy, grade 4 thrombocytopenia, grade 4 thrombocytopenia/grade 3 febrile neutropenia, and grade 4 supraventricular tachycardia. Twelve patients (30%) had >or=grade 2 neuropathy from this regimen. The overall response rate in patients with measurable disease was 58% (11 out of 19).


CONCLUSIONS
Dose-dense carboplatin/paclitaxel appears to be effective. However, based on dose limiting toxicities occurring when administering 6 cycles of treatment, it is not feasible. Given the neuropathy and thrombocytopenia, we do not recommend 6 cycles of this regimen without modification.
Tiersten
Amy D
AD
New York University Cancer Institute, New York, NY 10016, USA. amy.tiersten@med.nyu.edu
Sill
Michael W
MW
Knight
Danielle
D
Muggia
Franco
F
Garcia
Agustin A
AA
Swensen
Ron
R
Warshal
David P
DP
Mannel
Robert S
RS
Fracasso
Paula M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D016190:Carboplatin; D017239:Paclitaxel; D000069585:Filgrastim