Table 2. Response, toxicity and dose during IRI treatment.
|
IRI
|
CAPIRI
|
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| TA6 | TA6 | TA7 | TA6 | TA6 | TA7 | |||||
| UGT1A1 | TA6 | TA7 | TA7 | Total | TA6 | TA7 | TA7 | Total | ||
| Evaluable for response | N=44 | N=30 | N=3 | N=77 | P-value | N=61 | N=58 | N=8 | N=127 | P-value |
| Best overall response (%) | ||||||||||
| CR | 1 (2) | 3 (5) | 1 (13) | 5 (4) | ||||||
| PR | 7 (16) | 4 (13) | 11 (14) | 29 (48) | 22 (38) | 4 (50) | 55 (43) | |||
| SD | 27 (61) | 16 (53) | 3 (100) | 46 (60) | 27 (44) | 30 (52) | 2 (25) | 59 (46) | ||
| PD | 10 (23) | 10 (33) | 20 (26) | 4 (7) | 3 (5) | 1 (13) | 8 (6) | |||
| Response rate, %, (95% exact CI) | 15.9 (6.6:30.1) | 13.3 (3.8:30.7) | 0.0 (0%:70.8) | 14.3 (7.4:24.1) | 0.595L | 49.2 (36.1:62.3) | 43.1 (30.2:56.8) | 62.5 (24.5:91.5) | 47.2 (38.3:56.3) | 0.537L |
| Disease control, %, rate (95% exact CI) | 77.3 (62.2:88.5) | 66.7 (47.2:82.7) | 100 (29.2:100) | 74.0 (62.8:83.4) | 0.240L | 93.4 (84.1:98.2) | 94.8 (85.6:98.9) | 87.5 (47.3:99.7) | 93.7 (88.0:97.2) | 0.759L |
| TA6 | TA6 | TA7 | TA6 | TA6 | TA7 | |||||
| UGT1A1 | TA6 | TA7 | TA7 | Total | TA6 | TA7 | TA7 | Total | ||
| Evaluable for toxicity (grade 3–4) | N=46 | N=31 | N=3 | N=80 | P-value | N=65 | N=62 | N=11 | N=138 | P-value |
| Overall (%) | ||||||||||
| All cycles | 20 (43.5) | 12 (38.7) | 3 (100) | 35 (43.8) | Etrend 0.56 | 33 (50.8) | 33 (53.2) | 8 (72.7) | 74 (53.6) | Etrend 0.35 |
| Cycle 1 | 3 (6.5) | 4 (12.9) | 0 (0.0) | 7 (8.8) | FE 0.430 | 3 (4.6) | 6 (9.7) | 1 (9.1) | 10 (7.2) | Etrend 0.44 |
| Febrile neutropenia (%) | ||||||||||
| All cycles | 1 (2.2) | 6 (19.4) | 0 (0.0) | 7 (8.8) | FE 0.015 | 1 (1.5) | 4 (6.5) | 2 (18.2) | 7 (5.1) | Etrend 0.031 |
| Cycle 1 | 1 (2.2) | 2 (6.5) | 0 (0.0) | 3 (3.8) | FE 0.561 | 0 (0.0) | 1 (1.6) | 2 (18.2) | 3 (2.2) | Etrend 0.008 |
| Diarrhea | ||||||||||
| All cycles | 7 (15.2) | 7 (22.6) | 2 (66.7) | 16 (20.0) | Etrend 0.090 | 14 (21.5) | 14 (22.6) | 4 (36.4) | 32 (23.2) | Etrend 0.43 |
| Cycle 1 | 3 (6.5) | 4 (12.9) | 0 (0.0) | 7 (8.8) | FE 0.430 | 3 (4.6) | 6 (9.7) | 1 (9.1) | 10 (7.2) | Etrend 0.44 |
| TA6 | TA6 | TA7 | TA6 | TA6 | TA7 | |||||
| UGT1A1 | TA6 | TA7 | TA7 | Total | TA6 | TA7 | TA7 | Total | ||
| Evaluable for dose analysis | N=41 | N=29 | N=3 | N=73 | P-value | N=61 | N=58 | N=11 | N=130 | P-value |
| Number of cycles | ||||||||||
| Median (range) | 6 (3–17) | 6 (1–15) | 8 (4–8) | 6 (1–17) | 0.33$ | 9 (1–30) | 9 (1–32) | 9 (1–30) | 9 (1–32) | 0.66$ |
| Total dose ( g ) | ||||||||||
| Median (range) | 4.4 (1.7–11.2) | 3.6 (0.7–10.8) | 4.0 (2.6–4.9) | 4.2 (0.7–11.2) | 0.39$ | 3.8 (0.4–10.7) | 3.7 (0.4–14.7) | 3.0 (0.5–14.7) | 3.7 (0.4–14.7) | 0.44$ |
| Total dose ( g m −2 ) | ||||||||||
| Median (range) | 2.1 (1.0–6.0) | 2.0 (0.3–5.3) | 2.3 (1.4–2.4) | 2.1 (0.3–6.0) | 0.25$ | 2.1 (0.3–6.2) | 2.0 (0.2–8.0) | 1.9 (0.2–7.6) | 2.0 (0.2–8.0) | 0.51$ |
| Dose (mg m −2 ) per cycle | ||||||||||
| Median (range) | 347 (266–390) | 336 (272–364) | 302 (284–355) | 341 (266–390) | 0.45$ | 242 (84–257) | 242 (190–277) | 242 (156–253) | 242 (84–277) | 0.83$ |
| Reduction of IRI after cycle 1 | 8 | 5 | 2 | 15 | 0.45E | 12 | 13 | 3 | 28 | 0.62E |
| Cycle of first reduction (%) | ||||||||||
| Cycle 2–3 | 4 (50) | 4 (80) | 1 (50) | 9 (60) | 0.544L | 5 (42) | 9 (69) | 1 (33) | 15 (54) | 0.444L |
| Cycle 4–6 | 1 (13) | 1 (20) | 2 (13) | NS | 4 (33) | 2 (15) | 1 (33) | 7 (25) | NS | |
| Cycle 7–9 | 1 (13) | 1 (50) | 2 (13) | NS | 2 (17) | 1 (8) | 1 (33) | 4 (14) | NS | |
| Cycle ⩾10 | 2 (25) | 2 (13) | NS | 1 (8) | 1 (8) | 2 (7) | NS | |||
CAPIRI=irinotecan first-line combination therapy (250 mg m−2 every 3 weeks, with capecitabine); CI=confidence interval; CR=complete response; E=exact; Etrend=exact-values for trend; FE=Fisher's exact; IRI=irinotecan (350 mg m−2 every 3 weeks) second-line single-agent therapy; L=logistic regression; NS=statistically non-significant difference; PD=progressive disease; PR=partial response; SD=stable disease.
Response is defined as CR or PR, disease control as CR, PR or SD.
P-values are calculated by L, Etrend, E, FE or Kruskal–Wallis.
$Kruskal–Wallis.