Abstract
Background:Olaparib, an oral PARP inhibitor, has shown antitumour activity as monotherapy in patients with germline BRCA1/2 (gBRCA)-mutated breast and ovarian cancer. This study evaluated olaparib capsules in combination with liposomal doxorubicin (PLD) in patients with advanced solid tumours (NCT00819221).Methods:Patients received 28-day cycles of olaparib, continuously (days 1-28) or intermittently (days 1-7), plus PLD (40 mg m-2, day 1); seven olaparib dose cohorts (50-400 mg bid) were explored to determine the recommended dose. Assessments included safety, pharmacokinetics, pharmacodynamics and preliminary efficacy (objective response rate (ORR)).Results:Of 44 patients treated (ovarian, n=28; breast, n=13; other/unknown, n=3), two experienced dose-limiting toxicities (grade 3 stomatitis and fatal pneumonia/pneumonitis (200 mg per 28-day cycle); grade 4 thrombocytopenia (400 mg per 7-day cycle)). The maximum tolerated dose was not reached using continuous olaparib 400 mg bid plus PLD. Grade ≥3 and serious AEs were reported for 27 (61%) and 12 (27%) patients, respectively. No major pharmacokinetic interference was observed between olaparib and PLD. The ORR was 33% (n=14 out of 42; complete response, n=3). A total of 13 responders had ovarian cancer: 10 were platinum-sensitive, 11 had a gBRCA mutation.Conclusions:Continuous/intermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m-2) was generally tolerated and showed evidence of antitumour activity in ovarian cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 651-659 |
| Number of pages | 9 |
| Journal | British Journal of Cancer |
| Volume | 111 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Aug 12 2014 |
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Keywords
- advanced solid tumours
- liposomal doxorubicin
- olaparib
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Phase i study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours. / Del Conte, G.; Sessa, C.; Von Moos, R.; Viganò, L.; Digena, T.; Locatelli, A.; Gallerani, E.; Fasolo, A.; Tessari, A.; Cathomas, R.; Gianni, L.
In: British Journal of Cancer, Vol. 111, No. 4, 12.08.2014, p. 651-659.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phase i study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours
AU - Del Conte, G.
AU - Sessa, C.
AU - Von Moos, R.
AU - Viganò, L.
AU - Digena, T.
AU - Locatelli, A.
AU - Gallerani, E.
AU - Fasolo, A.
AU - Tessari, A.
AU - Cathomas, R.
AU - Gianni, L.
PY - 2014/8/12
Y1 - 2014/8/12
N2 - Background:Olaparib, an oral PARP inhibitor, has shown antitumour activity as monotherapy in patients with germline BRCA1/2 (gBRCA)-mutated breast and ovarian cancer. This study evaluated olaparib capsules in combination with liposomal doxorubicin (PLD) in patients with advanced solid tumours (NCT00819221).Methods:Patients received 28-day cycles of olaparib, continuously (days 1-28) or intermittently (days 1-7), plus PLD (40 mg m-2, day 1); seven olaparib dose cohorts (50-400 mg bid) were explored to determine the recommended dose. Assessments included safety, pharmacokinetics, pharmacodynamics and preliminary efficacy (objective response rate (ORR)).Results:Of 44 patients treated (ovarian, n=28; breast, n=13; other/unknown, n=3), two experienced dose-limiting toxicities (grade 3 stomatitis and fatal pneumonia/pneumonitis (200 mg per 28-day cycle); grade 4 thrombocytopenia (400 mg per 7-day cycle)). The maximum tolerated dose was not reached using continuous olaparib 400 mg bid plus PLD. Grade ≥3 and serious AEs were reported for 27 (61%) and 12 (27%) patients, respectively. No major pharmacokinetic interference was observed between olaparib and PLD. The ORR was 33% (n=14 out of 42; complete response, n=3). A total of 13 responders had ovarian cancer: 10 were platinum-sensitive, 11 had a gBRCA mutation.Conclusions:Continuous/intermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m-2) was generally tolerated and showed evidence of antitumour activity in ovarian cancer.
AB - Background:Olaparib, an oral PARP inhibitor, has shown antitumour activity as monotherapy in patients with germline BRCA1/2 (gBRCA)-mutated breast and ovarian cancer. This study evaluated olaparib capsules in combination with liposomal doxorubicin (PLD) in patients with advanced solid tumours (NCT00819221).Methods:Patients received 28-day cycles of olaparib, continuously (days 1-28) or intermittently (days 1-7), plus PLD (40 mg m-2, day 1); seven olaparib dose cohorts (50-400 mg bid) were explored to determine the recommended dose. Assessments included safety, pharmacokinetics, pharmacodynamics and preliminary efficacy (objective response rate (ORR)).Results:Of 44 patients treated (ovarian, n=28; breast, n=13; other/unknown, n=3), two experienced dose-limiting toxicities (grade 3 stomatitis and fatal pneumonia/pneumonitis (200 mg per 28-day cycle); grade 4 thrombocytopenia (400 mg per 7-day cycle)). The maximum tolerated dose was not reached using continuous olaparib 400 mg bid plus PLD. Grade ≥3 and serious AEs were reported for 27 (61%) and 12 (27%) patients, respectively. No major pharmacokinetic interference was observed between olaparib and PLD. The ORR was 33% (n=14 out of 42; complete response, n=3). A total of 13 responders had ovarian cancer: 10 were platinum-sensitive, 11 had a gBRCA mutation.Conclusions:Continuous/intermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m-2) was generally tolerated and showed evidence of antitumour activity in ovarian cancer.
KW - advanced solid tumours
KW - liposomal doxorubicin
KW - olaparib
UR - http://www.scopus.com/inward/record.url?scp=84906085351&partnerID=8YFLogxK
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U2 - 10.1038/bjc.2014.345
DO - 10.1038/bjc.2014.345
M3 - Article
VL - 111
SP - 651
EP - 659
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 4
ER -