Pegylated liposomal doxorubicin and carboplatin in advanced gynecologic Tumors: a prospective phase I/II study of the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR)

TY - JOUR

T1 - Pegylated liposomal doxorubicin and carboplatin in advanced gynecologic Tumors: a prospective phase I/II study of the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR)

AU - du Bois, A

AU - Burges, A

AU - Meier, W

AU - Pfisterer, J

AU - Schmalfeldt, B

AU - Richter, B

AU - Jackisch, C

AU - Staehle, A

AU - Kimmig, R

AU - Elser, G

AU - Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom

PY - 2006/1

Y1 - 2006/1

N2 - 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.PATIENTS AND 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.

AB - 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.PATIENTS AND 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.

KW - Adult

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Area Under Curve

KW - Carboplatin

KW - Dose-Response Relationship, Drug

KW - Doxorubicin

KW - Endometrial Neoplasms

KW - Female

KW - Humans

KW - Maximum Tolerated Dose

KW - Middle Aged

KW - Ovarian Neoplasms

KW - Polyethylene Glycols

KW - Prospective Studies

KW - Sarcoma

KW - Survival Rate

KW - Uterine Cervical Neoplasms

U2 - 10.1093/annonc/mdj032

DO - 10.1093/annonc/mdj032

M3 - SCORING: Journal article

C2 - 16282248

VL - 17

SP - 93

EP - 96

JO - ANN ONCOL

JF - ANN ONCOL

SN - 0923-7534

IS - 1

ER -