A phase II study of the potent PARP inhibitor, Rucaparib (PF-01367338, AG014699), with temozolomide in patients with metastatic melanoma demonstrating evidence of chemopotentiation
PURPOSE: poly(ADP ribose) polymerase inhibition has been shown to potentiate the cytotoxicity of DNA damaging agents. A phase I study of rucaparib and temozolomide showed that full-dose temozolomide could be given during PARP inhibition. We report the results of a phase II study of intravenous rucaparib 12 mg/m(2) and oral temozolomide 200 mg/m(2) on days 1-5 every 28 days in patients with advanced metastatic melanoma.
METHODS: Patients with chemotherapy naïve measurable metastatic melanoma, performance status ≤2 and good end-organ function were recruited. Treatment was given until progression. A two stage phase II design was used, with response rate the primary endpoint. Population pharmacokinetics and pharmacodynamics were also explored.
RESULTS: Forty-six patients were recruited with 37 patients receiving at least 2 cycles and 17 patients at least 6 cycles. Myelosuppression occurred with 25 patients (54 %) requiring a 25 % dose reduction in temozolomide. The response rate was 17.4 %, median time to progression 3.5 months, median overall survival 9.9 months, and 36 % of patients were progression-free at 6 months.
CONCLUSIONS: This study showed that temozolomide (150-200 mg/m(2)/day) can safely be given with a PARP inhibitory dose of rucaparib, increasing progression-free survival over historical controls in metastatic melanoma patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:71 |
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| Enthalten in: |
Cancer chemotherapy and pharmacology - 71(2013), 5 vom: 07. Mai, Seite 1191-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Plummer, Ruth [VerfasserIn] |
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| Links: |
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| Themen: |
7GR28W0FJI |
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| Anmerkungen: |
Date Completed 20.06.2013 Date Revised 02.12.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00280-013-2113-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM225159031 |
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| 100 | 1 | |a Plummer, Ruth |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A phase II study of the potent PARP inhibitor, Rucaparib (PF-01367338, AG014699), with temozolomide in patients with metastatic melanoma demonstrating evidence of chemopotentiation |
| 264 | 1 | |c 2013 | |
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| 500 | |a Date Completed 20.06.2013 | ||
| 500 | |a Date Revised 02.12.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: poly(ADP ribose) polymerase inhibition has been shown to potentiate the cytotoxicity of DNA damaging agents. A phase I study of rucaparib and temozolomide showed that full-dose temozolomide could be given during PARP inhibition. We report the results of a phase II study of intravenous rucaparib 12 mg/m(2) and oral temozolomide 200 mg/m(2) on days 1-5 every 28 days in patients with advanced metastatic melanoma | ||
| 520 | |a METHODS: Patients with chemotherapy naïve measurable metastatic melanoma, performance status ≤2 and good end-organ function were recruited. Treatment was given until progression. A two stage phase II design was used, with response rate the primary endpoint. Population pharmacokinetics and pharmacodynamics were also explored | ||
| 520 | |a RESULTS: Forty-six patients were recruited with 37 patients receiving at least 2 cycles and 17 patients at least 6 cycles. Myelosuppression occurred with 25 patients (54 %) requiring a 25 % dose reduction in temozolomide. The response rate was 17.4 %, median time to progression 3.5 months, median overall survival 9.9 months, and 36 % of patients were progression-free at 6 months | ||
| 520 | |a CONCLUSIONS: This study showed that temozolomide (150-200 mg/m(2)/day) can safely be given with a PARP inhibitory dose of rucaparib, increasing progression-free survival over historical controls in metastatic melanoma patients | ||
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| 700 | 1 | |a Lorigan, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Steven, Neil |e verfasserin |4 aut | |
| 700 | 1 | |a Scott, Lucy |e verfasserin |4 aut | |
| 700 | 1 | |a Middleton, Mark R |e verfasserin |4 aut | |
| 700 | 1 | |a Wilson, Richard H |e verfasserin |4 aut | |
| 700 | 1 | |a Mulligan, Evan |e verfasserin |4 aut | |
| 700 | 1 | |a Curtin, Nicola |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Diane |e verfasserin |4 aut | |
| 700 | 1 | |a Dewji, Raz |e verfasserin |4 aut | |
| 700 | 1 | |a Abbattista, Antonello |e verfasserin |4 aut | |
| 700 | 1 | |a Gallo, Jorge |e verfasserin |4 aut | |
| 700 | 1 | |a Calvert, Hilary |e verfasserin |4 aut | |
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