{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T17:42:04Z","timestamp":1760290924173,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T00:00:00Z","timestamp":1468540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>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\u2010sensitive ovarian, fallopian tube, and primary peritoneal cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>In phase 1, patients received carboplatin (at an area under the curve of 5) and increasing doses of pralatrexate until the maximum\u2010tolerated dose (MTD) of pralatrexate was achieved. The primary endpoint was the response rate. Additional endpoints were safety, response duration, progression\u2010free survival, overall survival, and pharmacokinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>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<jats:sup>2<\/jats:sup>. 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\u2010free 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Most patients responded to carboplatin\u2010pralatrexate combination. This regimen is well tolerated and effective in this patient population. <jats:bold><jats:italic>Cancer<\/jats:italic> 2016;122:3297\u20133306<\/jats:bold>. \u00a9 <jats:italic>2016 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.30196","type":"journal-article","created":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T12:20:42Z","timestamp":1468585242000},"page":"3297-3306","source":"Crossref","is-referenced-by-count":2,"title":["Phase 1 and 2 study of carboplatin and pralatrexate in patients with recurrent, platinum\u2010sensitive ovarian, fallopian tube, or primary peritoneal cancer"],"prefix":"10.1002","volume":"122","author":[{"given":"Marcela G.","family":"del Carmen","sequence":"first","affiliation":[{"name":"Division of Gynecologic Oncology, Massachusetts General Hospital Cancer Center Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff G.","family":"Supko","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Massachusetts General Hospital Cancer Center Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora K.","family":"Horick","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Massachusetts General Hospital Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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