A phase I study of capecitabine (CAP), carboplatin (CARB), paclitaxel (TAX) and external beam radiation therapy (EBRT) for patients with esophageal carcinoma (EC).
14044 Background: Chemoradiotherapy is used to treat esophageal cancer with curative intent or local symptom control. A phase I study of 5-FU + CARB + TAX + EBRT showed 100% RR and 50% pCR rate. CAP allows for fluoropyrimidine treatment without the inconvenience of an infusion pump. CARB allows for platinum treatment with less toxicity than cisplatin. We evaluated this combination of agents in a phase I study. METHODS: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus requiring local therapy received CAP (825 mg/m(2) bid on radiation days) + CARB (AUC 2 qweek) + TAX (60 mg/m(2) qweek) + EBRT (1.8 Gy qd to 50.4 Gy). DLT was defined as any grade 4 heme toxicity, grade 3 heme toxicity lasting ≥ 7 days, ≥ grade 3 N/V, diarrhea, or esophagitis lasting ≥ 4 days despite optimal medical management, grade 3 other toxicity, inability to deliver 75% of scheduled CAP dose, or treatment delay > 3 days. RESULTS: 13 pts were enrolled (10M, 3F). Median age was 62 (R- 48-78). EUS stage was uT3N0 (n=1), uT2N1 (n=1), or T3N1 (n=11). 2/3 pts had DLT at dose level 1 (both grade 4 esophagitis). Esophagectomy was performed in 2/3 patients, both pCR. Three pts were then enrolled at dose level -1 (CAP 600 mg/m(2) bid + CARB AUC 1.5 + TAX 45 mg/m(2)). One patient developed DLT (grade 3 esophagitis) so 7 more pts were added at this dose level. Overall, 3/10 patients at dose level -1 developed DLT (two grade 3 esophagitis, one grade 3 hypotension). Esophagectomy was performed in 6/10 pts - 2/6 had pCR; 6/6 had pathologic downstaging. CONCLUSIONS: MTD for this regimen was CAP 625 mg/m(2) bid + CARB AUC 1.5 + TAX 45 mg/m(2) with EBRT to 50.4 Gy. However, at the MTD, this regimen is relatively toxic with no significant improvement in rate of pCR. [Table: see text].
Kelsey, CR; Czito, BG; Bendell, JC; Willett, CG; Morse, MA; D'Amico, TA; Honeycutt, W; Franklin, A; Yu, D; Hurwitz, HI
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