Table 2.
Phase II and III trials of capecitabine in the neoadjuvant treatment of rectal cancer
| Trial | Phase | No. of patients | Regimen | Total RT dose (Gy) | Response rate | G 3/4 toxicities |
|---|---|---|---|---|---|---|
| Monotherapy | ||||||
| Kim et al29 | II | 45 | Cap 825 mg/m2 bid on days 1–14 q3wk × 2 cycles + LV 20 mg/m2 on days 1–14 q3wk × 2 cycles | 50.4 | 63% DS 31% pCR |
7% HFS, 4% diarrhea, 4% fatigue |
| Kim et al30 | II | 95 | Cap 825 mg/m2 bid with RT → resection → Cap 1250 mg/m2 on days 1–14 q3wk × 4 cycles | 50.0 | 76% DS 12% pCR |
3% diarrhea, 1% neutropenia |
| De Paoli et al27 | II | 53 | Cap 825 mg/m2 bid with RT → resection → Cap 1250 mg/m2 bid on days 1–14 q3wk × 4 cycles | 50.4 | 57% DS 24% pCR |
4% HFS, 4% leukopenia |
| Krishnan et al28 | II | 54 | Cap 825 mg/m2 with RT → resection → Cap 1250 mg/m2 bid on days 1–14 q3wk × 4 cycles | 52.5 | 51% DS 18% pCR |
4% proctitis, 2% fatigue, 2% diarrhea |
| Hoffheinz31 | III | 197 | Cap 1650 mg/m2 with RT → resection → Cap 2500 mg/m2 on days 1–14 q3wk x 5 cycles | 50.4 | 56% DS | 31% HFS, 25% leukopenia |
| Hoffheinz31 | III | 195 | 5-FU 225 mg/m2 or 1000 mg/m2 on days 1–5 q4wks with RT → resection → 5-FU 500 mg/m2 on days 1–5 q4wks x 4 cycles | 50.4 | 39% DS | 2% HFS, 35% leukopenia |
| In combination with irinotecan | ||||||
| Klautke et al38 | I/II | 28 | Cap 500–825 mg/m2 bid with RT + irinotecan 40 mg/m2 qwk | 55.8 | 51% DS 15% pCR |
Ph II: 20% diarrhea |
| Willeke et al37 | II | 36 | Cap 500 mg/m2 bid with RT + irinotecan 50 mg/m2 qwk | 50.4 | 55% DS 15% pCR |
25% leukopenia, 11% diarrhea |
| In combination with oxaliplatin | ||||||
| Rödel et al36 | I/II | 32 | Cap 825 mg/m2 bid on days 1–14 and 22–35 + oxaliplatin at 50–60 mg/m2 on days 1, 8, 22, and 29 | 50.4 | 55% DS 19% pCR |
Ph II: 8% diarrhea |
| Machiels et al35 | II | 40 | Cap 825 mg/m2 bid on days of RT + oxaliplatin 50 mg/m2 qwk | 45.0 | 53% DS 14% pCR |
30% diarrhea |
| Rödel et al32 | II | 110 | Cap 825 mg/m2 bid on days 1–14 and 22–35 + oxaliplatin 50 mg/m2 on days 1, 8, 22, and 29 → resection → Cap 1000 mg/m2 BID on days 1–14 + oxaliplatin 130 mg/m2 q3wk × 4 cycles | 50.4 | 67% DS 16% pCR |
12% diarrhea, 6% nausea/vomiting, 4% leukopenia |
| Chua et al33 | II | 105 | Cap 1000 mg/m2 bid on days 1–14 + oxaliplatin 130 mg/m2 q3wk × 4 cycles → Cap 825 mg/m2 BID + RT → resection → Cap 1250 mg/m2 bid on days 1–14 q3wk × 4 cycles | 54.0 | 53% DS 20% pCR |
10% diarrhea, 9% CV/thromboembolic, 7% fatigue, 3% HFS |
| Gérard et al34 | III | 299 | Cap 800 mg/m2 bid with RT | 45.0 | 13.9% pCR | 4% heme, 3% diarrhea |
| 299 | Cap 800 mg/m2 bid with RT + oxaliplatin 50 mg/m2 qwk | 50.0 | 19.2% pCR | 13% diarrhea, 5% heme | ||
| In combination with targeted treatments | ||||||
| Machiels et al39 | I/II | 40 | Cap 650–825 mg/m2 bid with RT + cetuximab 400 mg/m2 1 week prior to RT then 250 mg/m2 qwk × 5 | 45.0 | 38% DS 5% pCR |
Phase II: 17% diarrhea, 8% pain |
| Rödel et al40 | I/II | 60 | Cap 500–825 mg/m2 bid on days 1–14 and 22–35 + oxaliplatin 50 mg/m2 on days 1, 8, 22, and 29 + cetuximab 400 mg/m2 1 week prior to RT then 250 mg/m2 qwk × 5 | 50.4 | 47% DS 9% pCR |
19% diarrhea, 6% leukopenia |
| Velenik et al64† | II | 39 | Bev 15 mg/kg q2wk prior to RT → Bev 15 mg/kg on weeks 3, 5, 7 + Cap 825 mg/m2 bid with RT | 50.4 | 56% DS 16% pCR |
8% proteinuria, 4% diarrhea |
Note:
†
denotes abstracts.
Abbreviations: RT, radiotherapy; DS, tumor downstaging; HFS, hand–foot syndrome; pCR, pathologic complete response; bid, twice daily; Cap, capecitabine; Bev, bevacizumab; LV, leucovorin; qwk, weekly.