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Phase 1 and 2 study of carboplatin and pralatrexate in patients with recurrent, platinum‐sensitive ovarian, fallopian tube, or primary peritoneal cancer
Author(s) -
del Carmen Marcela G.,
Supko Jeff G.,
Horick Nora K.,
RauhHain J. Alejandro,
Clark Rachel M.,
Campos Susana M.,
Krasner Carolyn N.,
Atkinson Tina,
Birrer Michael J.
Publication year - 2016
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.30196
Subject(s) - medicine , carboplatin , fallopian tube cancer , ovarian cancer , adverse effect , clinical endpoint , phases of clinical research , fallopian tube , oncology , surgery , gastroenterology , clinical trial , cancer , chemotherapy , cisplatin
BACKGROUND The objective of this phase 1 and 2 trial was to identify the appropriate dose of combined carboplatin and pralatrexate for patients with recurrent, platinum‐sensitive ovarian, fallopian tube, and primary peritoneal cancer. METHODS In phase 1, patients received carboplatin (at an area under the curve of 5) and increasing doses of pralatrexate until the maximum‐tolerated dose (MTD) of pralatrexate was achieved. The primary endpoint was the response rate. Additional endpoints were safety, response duration, progression‐free survival, overall survival, and pharmacokinetics. RESULTS Thirty patients were enrolled in phase 1, and 20 were enrolled in phase 2. Of all 50 patients, 49 completed the study. The mean patient age was 59 years, and patients completed a median of 6 cycles. The MTD for pralatrexate was 105 mg/m 2 . The clinical benefit rate (complete responses plus partial responses plus stable disease) was 86%. Of 26 patients who received the MTD, 12 had a partial response, 11 had stable disease, and 2 had disease progression. The progression‐free survival rate at 3 and 6 months was 87% and 79%, respectively; and the overall survival rate was 98% at 6 and 12 months and 66% at 24 months. Of 30 patients, 18 (60%) in phase 1 experienced an adverse event of any grade; and, of those, 4 patients (13%) had a grade 3 or greater adverse event. In phase 2, 12 patients (60%) had an adverse event of any grade, and 4 (20%) had grade 3 or greater toxicity. There was a significant reduction in the total body clearance of pralatrexate when it was received concurrently with carboplatin. CONCLUSIONS Most patients responded to carboplatin‐pralatrexate combination. This regimen is well tolerated and effective in this patient population. Cancer 2016;122:3297–3306 . © 2016 American Cancer Society .