Introduction
Methods
Results
Incidence
Population | Prior MBC Tx | Ref | Ixabepilone (i.v.) dose/schedule |
N
| Median cycles | Incidence of Neuropathy | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
All grades, % | Grade 3, % | Grade 4, % | |||||||||
Sensory | Motor | Sensory | Motor | Sensory | Motor | ||||||
Neoadjuvant phase II | |||||||||||
Untreated | 0 | [17] | 40 mg/m2 day 1 Q3w | 164 | 4 | 20 | NR | 1 | NR | 0 | NR |
Metastatic phase I/II | |||||||||||
A/T pretreated | 0–3 | [18] | 40 mg/m2 day 1 Q3w + capecitabinea
| 62 | 4 | 74 | 2 | 19 | 2 | 0 | 0 |
Metastatic phase II | |||||||||||
T naive | Any | [19] | 6 mg/m2 days 1–5 Q3w | 23 | 8 | 52 | 8 | 0 | 4 | 0 | 0 |
A pretreated | 0 | [21] | 40 mg/m2 day 1 Q3w | 65 | 6 | 71 | 6 | 20 | 5 | 0 | 0 |
T pretreated | 0–9 | [20] | 6 mg/m2 days 1–5 Q3w | 37 | 54 | 0 | 3 | 0 | 0 | 0 | |
A pretreated/T resistant | 1–4 | [22] | 40 mg/m2 day 1 Q3w | 49 | 3 | 63 | 2 | 12 | 0 | 0 | 0 |
A/T/C resistant | 1–3 | [14] | 40 mg/m2 day 1 Q3w | 126 | 4 | 60 | 10 | 13 | <1 | 1 | 0 |
Metastatic phase III | |||||||||||
A pretreated/T resistant | 0–3 | [15] | 40 mg/m2 day 1 Q3w + capecitabineb
| 369 | 5 | 67 | 16 | 20 | 5 | <1 | 0 |
Capecitabinec
| 368 | 4 | 16 | <1 | 0 | 0 | 0 | 0 | |||
A/T pretreated | 0–2 | [16] | 40 mg/m2 day 1 Q3w + capecitabineb
| 595 | 6 | 66 | 22 | 4 | 1 | 0 | |
Capecitabinec
| 603 | 5 | 21 | 1 | 0 | <1 | 0 |
Factors affecting neuropathy
Risk factors
Grade 3/4 neuropathy, % (events/patients) | Median cumulative dose (mg/m2) | Hazard ratio | Cox regression, P value | |
---|---|---|---|---|
Baseline neuropathy | ||||
>Grade 0 | 22.8 (77/338) | 360.3 | 1.44 | 0.007 |
Grade 0 | 19.5 (234/1,202) | 501.0 | ||
Diabetes | ||||
Yes | 22.3 (25/112) | Not estimable | 1.21 | 0.375 |
No | 20.0 (286/1,428) | 477.9 | ||
Age | ||||
≥65 | 18.3 (42/229) | 561.3 | 1.19 | 0.318 |
17–65 | 20.5 (269/1,311) | 477.9 | ||
Prior taxane | ||||
Yes | 20.0 (276/1,379) | 543.8 | 0.35 | 0.018 |
No | 21.7 (35/161) | 306.9 | ||
Prior other chemotherapy | ||||
Yes | 16.2 (49/303) | Not estimable | 0.75 | 0.119 |
No | 21.2 (262/1,237) | 441.3 |
Dose per cycle
Cumulative dose
Study [reference] | 046 [15] | 048 [16] |
Number of patients | 369 | 595 |
Grade 3/4 PN, n (%) | 79 (21) | 140 (24) |
Time (months, 95% CI), among patients with grade 3/4 PN | 2.9 (2.4–3.4) | 3.0 (2.7–3.6) |
Time (months, 95% CI), among all treated patientsa
| 13.3 (9.3–15.5) | (10.3–NR)b
|
Management
Resolution of neuropathy
Ixabepilone | Ixabepilone + capecitabine | ||
---|---|---|---|
Study [reference] | 081 [14] | 046 [15] | 048 [16] |
Patient number | 126 | 369 | 595 |
Grade 3/4 PN, n (%) | 17 (14) | 79 (21) | 140 (24) |
Resolution | |||
Resolutiona, n (%) | 13 (76) | 70 (89) | 120 (86) |
Median time to resolution, weeks (95% CI) | 5.4 (3.3–11.4) | 6.0 (4.6–7.6) | 6.2 (5.0–8.7) |
Improvement | |||
Improvement, n (%) | 14 (82) | 70 (89) | 124 (89) |
Median time to improvement, weeks (95% CI) | 4.6 (0.9–6.1) | 4.1 (2.9–6.0) | 4.5 (3.3–5.1) |