Randomized phase II trial of carboplatin and paclitaxel with or without lonafarnib in first-line treatment of epithelial ovarian cancer stage IIB-IV
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Randomized phase II trial of carboplatin and paclitaxel with or without lonafarnib in first-line treatment of epithelial ovarian cancer stage IIB-IV. / Meier, Werner; du Bois, Andreas; Rau, Jörn; Gropp-Meier, Martina; Baumann, Klaus; Huober, Jens; Wollschlaeger, Kerstin; Kreienberg, Rolf; Canzler, Ulrich; Schmalfeldt, Barbara; Wimberger, Pauline; Richter, Barbara; Schröder, Willibald; Belau, Antje; Stähle, Anne; Burges, Alexander; Sehouli, Jalid.
In: GYNECOL ONCOL, Vol. 126, No. 2, 08.2012, p. 236-40.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Randomized phase II trial of carboplatin and paclitaxel with or without lonafarnib in first-line treatment of epithelial ovarian cancer stage IIB-IV
AU - Meier, Werner
AU - du Bois, Andreas
AU - Rau, Jörn
AU - Gropp-Meier, Martina
AU - Baumann, Klaus
AU - Huober, Jens
AU - Wollschlaeger, Kerstin
AU - Kreienberg, Rolf
AU - Canzler, Ulrich
AU - Schmalfeldt, Barbara
AU - Wimberger, Pauline
AU - Richter, Barbara
AU - Schröder, Willibald
AU - Belau, Antje
AU - Stähle, Anne
AU - Burges, Alexander
AU - Sehouli, Jalid
N1 - Copyright © 2012 Elsevier Inc. All rights reserved.
PY - 2012/8
Y1 - 2012/8
N2 - OBJECTIVES: This study evaluates whether a molecular targeted therapy with the farnesyltransferase inhibitor lonafarnib added to standard chemotherapy in first-line treatment of advanced ovarian cancer (OC) could improve progression-free (PFS) and overall survival (OS).PATIENTS AND METHODS: We performed a prospective randomized phase II study to compare standard therapy carboplatin (C; AUC 5) and paclitaxel (T; 175 mg/m(2)) in primary advanced OC with or without lonafarnib (L). Lonafarnib was given in a dose of 100mg orally twice a day during chemotherapy and was increased afterwards to 200mg up to six months as a maintenance therapy.RESULTS: 105 patients were recruited (53 patients were randomized to receive LTC, 52 to TC). Hematologic toxicity was similar in both arms. Grade 3 and 4 non-hematological toxicity, occurred significantly more often with LTC (23% versus 4%, p=0.005) and was associated with a higher dropout rate. PFS and OS were not significantly different among both arms. The LTC arm showed inferiority in the stratum with residual tumor of more than 1cm: median PFS was 11.5 months (95% CI: 7.4-14.2) compared with 16.4 (95% CI: 10.3-40.4) for TC (p=0.0141; HR=0.36 (95% CI: 0.15-0.84)) with median OS 20.6 months (95% CI: 13.1-31.0) and 43.4 months (95% CI: 15.7-) for the TC arm (p=0.012; HR=0.32 (95% CI: 0.13-0.8)).CONCLUSION: The addition of lonafarnib did not improve PFS or OS. Patients with a residual tumor of more than 1cm had significantly shorter PFS and OS. Incorporation of lonafarnib into future studies for primary therapy of OC is not recommended.
AB - OBJECTIVES: This study evaluates whether a molecular targeted therapy with the farnesyltransferase inhibitor lonafarnib added to standard chemotherapy in first-line treatment of advanced ovarian cancer (OC) could improve progression-free (PFS) and overall survival (OS).PATIENTS AND METHODS: We performed a prospective randomized phase II study to compare standard therapy carboplatin (C; AUC 5) and paclitaxel (T; 175 mg/m(2)) in primary advanced OC with or without lonafarnib (L). Lonafarnib was given in a dose of 100mg orally twice a day during chemotherapy and was increased afterwards to 200mg up to six months as a maintenance therapy.RESULTS: 105 patients were recruited (53 patients were randomized to receive LTC, 52 to TC). Hematologic toxicity was similar in both arms. Grade 3 and 4 non-hematological toxicity, occurred significantly more often with LTC (23% versus 4%, p=0.005) and was associated with a higher dropout rate. PFS and OS were not significantly different among both arms. The LTC arm showed inferiority in the stratum with residual tumor of more than 1cm: median PFS was 11.5 months (95% CI: 7.4-14.2) compared with 16.4 (95% CI: 10.3-40.4) for TC (p=0.0141; HR=0.36 (95% CI: 0.15-0.84)) with median OS 20.6 months (95% CI: 13.1-31.0) and 43.4 months (95% CI: 15.7-) for the TC arm (p=0.012; HR=0.32 (95% CI: 0.13-0.8)).CONCLUSION: The addition of lonafarnib did not improve PFS or OS. Patients with a residual tumor of more than 1cm had significantly shorter PFS and OS. Incorporation of lonafarnib into future studies for primary therapy of OC is not recommended.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Carboplatin
KW - Disease-Free Survival
KW - Female
KW - Humans
KW - Middle Aged
KW - Neoplasm Staging
KW - Neoplasms, Glandular and Epithelial
KW - Ovarian Neoplasms
KW - Paclitaxel
KW - Piperidines
KW - Prospective Studies
KW - Pyridines
KW - Survival Analysis
KW - Young Adult
U2 - 10.1016/j.ygyno.2012.04.050
DO - 10.1016/j.ygyno.2012.04.050
M3 - SCORING: Journal article
C2 - 22564713
VL - 126
SP - 236
EP - 240
JO - GYNECOL ONCOL
JF - GYNECOL ONCOL
SN - 0090-8258
IS - 2
ER -