Pazopanib with Topotecan weekly for patients with platinum-resistant or intermediate-sensitive recurrent ovarian cancer: results of a multicentre, open label phase I/II study (TOPAZ)
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Pazopanib with Topotecan weekly for patients with platinum-resistant or intermediate-sensitive recurrent ovarian cancer: results of a multicentre, open label phase I/II study (TOPAZ). / Chekerov, Radoslav; Arndt, Tjadina; Pietzner, Klaus; Canzler, Ulrich; Wimberger, Pauline; Strauß, Hans-Georg; Mahner, Sven; Woelber, Linn; de Gregorio, Nikolaus; Stocker, Gertraud; von Abel, Ekkehard; Neunhoeffer, Tanja; Belau, Antje Kristina; Mustea, Alexander; Yalinkaya, Isil; Braicu, Elena Ioana; Richter, Rolf; Sehouli, Jalid; NOGGO ovarian cancer study group.
In: J CANCER RES CLIN, Vol. 149, No. 10, 08.2023, p. 7637-7649.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Pazopanib with Topotecan weekly for patients with platinum-resistant or intermediate-sensitive recurrent ovarian cancer: results of a multicentre, open label phase I/II study (TOPAZ)
AU - Chekerov, Radoslav
AU - Arndt, Tjadina
AU - Pietzner, Klaus
AU - Canzler, Ulrich
AU - Wimberger, Pauline
AU - Strauß, Hans-Georg
AU - Mahner, Sven
AU - Woelber, Linn
AU - de Gregorio, Nikolaus
AU - Stocker, Gertraud
AU - von Abel, Ekkehard
AU - Neunhoeffer, Tanja
AU - Belau, Antje Kristina
AU - Mustea, Alexander
AU - Yalinkaya, Isil
AU - Braicu, Elena Ioana
AU - Richter, Rolf
AU - Sehouli, Jalid
AU - NOGGO ovarian cancer study group
N1 - © 2023. The Author(s).
PY - 2023/8
Y1 - 2023/8
N2 - PURPOSE: Pazopanib has promising antiangiogenetic activity in solid cancers. The investigator-initiated phase I/II trial evaluated the combination of Topotecan with Pazopanib in platinum-resistant or intermediate-sensitive recurrent ovarian cancer (ROC).METHODS: Patients (≥ 18 years) with first or second recurrence were enrolled in this multicentre open-label trial. Phase I analysed Topotecan 4 mg/m2 (day 1, 8, 15, ever 28 days) for six cycles to identify the maximum tolerated dose (MTD) of Pazopanib added in a dose-escalating scheme with 400 mg starting dose. The phase II analysed safety and efficacy aspects. For all patients with clinical remission a maintenance with Pazopanib until progression was allowed. This trial is registered with ClinicalTrials.gov, number NCT01600573.RESULTS: Between June 2012 and February 2017, 11 patients were enrolled in the phase I, and 50 patients in the phase II study. The MTD of Pazopanib was determined by 400 mg/daily. Haematological and liver toxicities determined the dose limiting toxicities (DLT) and the most common grade 3-4 adverse events: leucopenia (25%), neutropenia (22%), thrombocytopenia (19%), accumulation of cholestatic (20%) and hepatocellular damage (15%), which often caused dose modifications, but no new life-threatening events. Overall response was 16% and clinical benefit rate 68%. Median progression-free survival (PFS) was 3.5 months (95% CI 2.0-5.0). Due to early progression only 20% of the patients were able to start with maintenance treatment.CONCLUSION: The combination of pazopanib and weekly topotecan is feasible, resulting in a manageable haematological and liver toxicity, but despite its encouraging response rate, was not associated with a significant survival benefit.
AB - PURPOSE: Pazopanib has promising antiangiogenetic activity in solid cancers. The investigator-initiated phase I/II trial evaluated the combination of Topotecan with Pazopanib in platinum-resistant or intermediate-sensitive recurrent ovarian cancer (ROC).METHODS: Patients (≥ 18 years) with first or second recurrence were enrolled in this multicentre open-label trial. Phase I analysed Topotecan 4 mg/m2 (day 1, 8, 15, ever 28 days) for six cycles to identify the maximum tolerated dose (MTD) of Pazopanib added in a dose-escalating scheme with 400 mg starting dose. The phase II analysed safety and efficacy aspects. For all patients with clinical remission a maintenance with Pazopanib until progression was allowed. This trial is registered with ClinicalTrials.gov, number NCT01600573.RESULTS: Between June 2012 and February 2017, 11 patients were enrolled in the phase I, and 50 patients in the phase II study. The MTD of Pazopanib was determined by 400 mg/daily. Haematological and liver toxicities determined the dose limiting toxicities (DLT) and the most common grade 3-4 adverse events: leucopenia (25%), neutropenia (22%), thrombocytopenia (19%), accumulation of cholestatic (20%) and hepatocellular damage (15%), which often caused dose modifications, but no new life-threatening events. Overall response was 16% and clinical benefit rate 68%. Median progression-free survival (PFS) was 3.5 months (95% CI 2.0-5.0). Due to early progression only 20% of the patients were able to start with maintenance treatment.CONCLUSION: The combination of pazopanib and weekly topotecan is feasible, resulting in a manageable haematological and liver toxicity, but despite its encouraging response rate, was not associated with a significant survival benefit.
KW - Female
KW - Humans
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Carcinoma, Ovarian Epithelial/drug therapy
KW - Leukopenia/chemically induced
KW - Neoplasm Recurrence, Local/drug therapy
KW - Ovarian Neoplasms
KW - Platinum/pharmacology
KW - Topotecan/therapeutic use
U2 - 10.1007/s00432-023-04647-9
DO - 10.1007/s00432-023-04647-9
M3 - SCORING: Journal article
C2 - 37000264
VL - 149
SP - 7637
EP - 7649
JO - J CANCER RES CLIN
JF - J CANCER RES CLIN
SN - 0171-5216
IS - 10
ER -
