McWilliams, Robert R.;
Mahoney, Michelle R.;
Marchello, Benjamin T.;
Jatoi, Aminah;
Krewer, Keith D.;
Ames, Matthew M.;
Schneider, Daniel Jay;
Seeger, Grant R.;
Mowat, Rex B.;
Alberts, Steven R.;
Goetz, Matthew P.
Pharmacogenetic dosing by UGT1A1 genotype as first-line therapy for advanced small-bowel adenocarcinoma: A North Central Cancer Treatment Group (NCCTG) trial
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Medientyp:
E-Artikel
Titel:
Pharmacogenetic dosing by UGT1A1 genotype as first-line therapy for advanced small-bowel adenocarcinoma: A North Central Cancer Treatment Group (NCCTG) trial
Beteiligte:
McWilliams, Robert R.;
Mahoney, Michelle R.;
Marchello, Benjamin T.;
Jatoi, Aminah;
Krewer, Keith D.;
Ames, Matthew M.;
Schneider, Daniel Jay;
Seeger, Grant R.;
Mowat, Rex B.;
Alberts, Steven R.;
Goetz, Matthew P.
Erschienen:
American Society of Clinical Oncology (ASCO), 2012
Beschreibung:
<jats:p> 314 </jats:p><jats:p> Background: Small bowel adenocarcinoma (SB-ACA) is rare, having little prospective data guiding management. A prior phase I study evaluated UGT1A1 genotype specific dosing of oxaliplatin, irinotecan, and capecitabine. Our prospective, multicenter clinical trial assessing tumor response in pts having metastatic SB-ACA, used a similar dosing strategy. </jats:p><jats:p> Methods: Genotypes were determined via central lab. Previously untreated pts were dosed by UGT1A1*28 genotypes 6/6, 6/7, and 7/7 receiving 100/85/85 mg/m<jats:sup>2</jats:sup> oxaliplatin d1, 150/150/75 mg/m<jats:sup>2</jats:sup> irinotecan d1, and 1600/400/200 mg/m<jats:sup>2</jats:sup> capecitabine (BID) d2-15 of 21 days. The study design was such that 1 confirmed response in 16 pts expanded enrollment to 33 pts, with 7 required for demonstrating efficacy. </jats:p><jats:p> Results: 28 pts (13-6/6, 10-6/7, 5-7/7) have been enrolled [75% male, mean age 62.5 (range 41-77)]. Location of primary included: duodenum (63%), jejunum (26%), and ileum (7%), with pts having >1 metastatic site (abdominal-41%, bone-7%, liver-56%, lung-30%, nodal-52%, subcutaneous-4%, other-19%). Gr 3+ treatment related toxicity was not significantly different by genotype (50%-6/6, 44%-6/7, 20%-7/7, p=0.48) and included (pts): diarrhea(5), vomiting(5), leukopenia(5), neutropenia(7), and nausea(6). 57% (13 of 23) pts achieved responses during therapy, with a confirmed response rate of 39% (95% CI 0-58%). 18 have died, with a median follow-up of 8.3 mos (range 0-43). </jats:p><jats:p> Conclusions: UGT1A1 genotype directed dosing with oxaliplatin, irinotecan, and capecitabine appears to result in prolonged response in this population. Larger studies are needed to determine comparability to CapeOx alone or if response/toxicity differs among genotypes. Supported by NIH Grant CA25224, Sanofi-Aventis, and Pfizer. </jats:p><jats:p> [Table: see text] </jats:p>