Phase II evaluation of paclitaxel and carboplatin in the treatment of carcinosarcoma of the uterus: a Gynecologic Oncology Group study.
OBJECTIVE
Platinum and taxane compounds have demonstrated activity in uterine carcinosarcoma (malignant mixed Mullerian tumor). Ifosfamide plus paclitaxel is the regimen with established superiority based on a randomized phase III trial conducted through the Gynecologic Oncology Group. However, the toxicity, multiday schedule, and limited activity of this regimen support further development of novel regimens. Our primary objective was to estimate the antitumor activity and toxicity of paclitaxel plus carboplatin in patients with uterine carcinosarcomas.


METHODS
Eligible patients had advanced stage (III or IV), persistent or recurrent measurable disease, and no prior chemotherapy. Patients received paclitaxel at 175 mg/m(2) intravenously (IV) over 3 hours plus carboplatin (area under the serum concentration-time curve = 6) IV over 30 minutes every 3 weeks until disease progression or until adverse effects occurred. Common Terminology Criteria for Adverse Events v3.0 was used to grade adverse events.


RESULTS
Fifty-five patients were entered onto the study with nine being excluded from analysis, leaving 46 evaluable for analysis. Treatment was well tolerated with expected hematologic toxicity and minimal nonhematologic grade 4 toxicity (one cardiovascular and two pain) with 59% of patients completing six or more cycles of chemotherapy. The proportions of patients with confirmed complete and partial responses were 13% and 41%, respectively, resulting in a total overall response rate of 54% (95% CI, 37% to 67%).


CONCLUSIONS
Paclitaxel plus carboplatin demonstrates antitumor activity against uterine carcinosarcoma with acceptable toxicity and warrants further evaluation in phase III randomized trials.
Powell
Matthew A
MA
Washington University School of Medicine, Department of Obstetrics/Gynecology, 4911 Barnes-Jewish Hospital Plaza, St Louis, MO 63110, USA. powellm@wudosis.wustl.edu
Filiaci
Virginia L
VL
Rose
Peter G
PG
Mannel
Robert S
RS
Hanjani
Parviz
P
Degeest
Koen
K
Miller
Brigitte E
BE
Susumu
Nobuyuki
N
Ueland
Frederick R
FR
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001707:Biopsy, Needle; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002296:Carcinosarcoma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011336:Probability; D011379:Prognosis; D015397:Program Evaluation; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology
D016190:Carboplatin; D017239:Paclitaxel