Pegylated liposomal doxorubicin and carboplatin in advanced gynecologic tumors: a prospective phase I/II study of the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR).
BACKGROUND
Single-agent platinum and single-agent pegylated liposomal doxorubicin (PLD) are both effective in the treatment of gynecologic malignancies. Based on evidence that combination platinum-containing regimens offer superior efficacy versus single-agent regimens, we conducted this study to determine the maximum tolerated dose (MTD) of PLD in combination with carboplatin.


METHODS
In this phase I/II dose-finding study, six courses of PLD (20, 30, 40 or 50 mg/m2) and carboplatin (AUC 6) were administered every 28 days to women with advanced gynecologic malignancies. Three to six patients were treated at each dose level; an additional 12 patients were treated at the MTD.


RESULTS
PLD 40 mg/m2 was identified as the MTD when administered with carboplatin. Five of 18 patients experienced a dose-limiting toxicity at the MTD; two patients had grade 3/4 neutropenia, and one each had grade 3 emesis and grade 3 thrombocytopenia and thrombosis. No patient developed cardiotoxicity. In 11 patients evaluable for response, there were two complete responses, two partial responses and four patients with stable disease.


CONCLUSIONS
The MTD for PLD when administered in combination with carboplatin is 40 mg/m2. This regimen is well tolerated and offers promising activity in women with advanced gynecologic malignancies.
du Bois
A
A
HSK, Dr Horst Schmidt Klinik, Department of Gynecology & Gynecologic Oncology, Wiesbaden, Germany. dubois.hsk-wiesbaden@uumail.de
Burges
A
A
Meier
W
W
Pfisterer
J
J
Schmalfeldt
B
B
Richter
B
B
Jackisch
C
C
Staehle
A
A
Kimmig
R
R
Elser
G
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011446:Prospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000401:mortality
C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin