Table 1.
Results of clinical trials with fludarabine as single-agent or in combination given intravenously or orally
| References | RCT | n | Median age | Route | Treatment regimen | OR (%) | CR (%) | PFS (m) | Neutropenia (%) Grade 3–4 | Infections (%) Grade 3–4 |
|---|---|---|---|---|---|---|---|---|---|---|
| Single-agent fludarabine in previously treated CLL | ||||||||||
| Keating2 | no | 68 | 60 | IV | F 25–30 mg/m2 × 5/28d | 57 | 13 | 16 (OS) | 56 (courses) | na |
| Boogaerts13 | no | 78 | 63.4 | oral | F 40 mg/m2 × 5/28d | 51,3 | 17,9 | na | 53.8 | 7.7 |
| Single-agent fludarabine in untreated CLL | ||||||||||
| Leporrier34 | yes | 341 | 62 | IV | F 25 mg/m2 × 5/28d | 71,1 | 40,1 | 31.7 | 38 (courses?) | na |
| Rai14 | yes | 179 | 64 | IV | F 25 mg/m2 × 5/28d | 63 | 20 | 20 | 27 | 16 |
| Eichhorst27 | yes | 164 | 59 | IV | F 25 mg/m2 × 5/28d | 83 | 7 | 20 | 26 | 8.7 |
| Flinn28 | yes | 137 | 61 | IV | F 25 mg/m2 × 5/28d | 59 | 7 | 19 | 63 | na |
| Catovsky29 | yes | 196 | 64 | IV-oral | F 25 (40) mg/m2 × 5/28d | 80 | 15 | 28 | na | na |
| Rossi15 | no | 81 | 61.2 | oral | F 40 mg/m2 × 5/28d | 80,2 | 12,3 | 27 | 32.1 | 4.9 |
| Shustik16 | no | 126 | 60.9 | oral | F 40 mg/m2 × 5/28d | 64 | 18 | 15.3 | 51 | na |
| Fludarabine plus cyclophosphamide in treated CLL | ||||||||||
| Wierda21 | no | 111 | 59 | IV | F 30 mg/m2 × 3/28d + C 300 mg/m2 × 3/28d | 67 | 12 | 36 | 47 (courses) | na |
| Robak22 | yes | 276 | 63 | IV | F 25 mg/m2 × 3/28d + C 250 mg/m2 × 3/28d | 58 | 13 | 20.6 | 40 | 19 |
| Forconi32 | no | 12 | ≥65 | oral | F 25 mg/m2 × 4/28d + C 120 mg/m2 × 4/28d | 83,5 | 25 | 48 (EFS) | 25 | 16.6 |
| Fludarabine plus cyclophosphamide in untreated CLL | ||||||||||
| Eichhorst27 | yes | 164 | 58 | IV | F 25 mg/m2 × 3/28d + C 250 mg/m2 × 3/28d | 94 | 24 | 48 | 55.5 | 8.7 |
| Flinn28 | yes | 141 | 61 | IV | F 20 mg/m2 × 5/28d + C 600 mg/m2/28d | 74 | 23 | 32 | 69 | na |
| Catovsky29 | yes | 196 | 65 | IV-oral | F 25(24) mg/m2 × 3(5)/28d + C 250(120) mg/m2 × 3(5)/28d | 95 | 38 | 43 | na | na |
| Hallek30 | yes | 409 | 61 | IV | F 25 mg/m2 × 3/28d + C 250 mg/m2 × 3/28d | 95 | 27 | 32 | 20,9 | 14.8 |
| Cazin31 | no | 75 | 57 | oral | F 30 mg/m2 × 5/28d + C 200 mg/m2 × 5/28d | 80 | 53 | 60 | 52 | 16 |
| Forconi32 | no | 14 | ≥65 | oral | F 25 mg/m2 × 4/28d + C 120 mg/m2 × 4/28d | 100 | 61.5 | 48(EFS) | 21 | 0 |
| Laurenti33 | no | 35 | 68 | oral | F 30 mg/m2 × 3/28d + C 250 mg/m2 × 3/28d | 77 | 40 | 23 | 45.7 | 0 |
| Fludarabine plus alemtuzumab in treated CLL | ||||||||||
| Elter23 | no | 36 | 61.4 | IV | F 30 mg/m2 × 3/28d + A 30 mg × 3/28d | 83 | 30 | 35.6(OS) | 26 (courses) | 5 (courses) |
| Hwang24 | no | 5 | 72 | oral-sc | F 40 mg/m2 × 5/28d + A 30 mg/d1–3–5/28d | 100 | 60 | na | na | na |
| Fludarabine-cyclophosphamide plus alemtuzumab in treated CLL | ||||||||||
| Elter25 | no | 55 | 63 | IV-sc | F 25 mg/m2 × 3 + C 200 mg/m2 × 3 + A 30 mg × 3/28d | 83 | 38 | na | na | na |
| Montillo26 | no | 25 | 57 | oral-sc | F 40 mg/m2 × 3 + C 250 mg/m2 × 3 + A10–20 mg × 3/28d | 79 | 37 | na | 43 (courses) | na |
Abbreviations: C, cyclophosphamide; CR, complete response; EFS, event free survival; F, fludarabine; Infections (%), % of patients treated; n, number of evaluable patients; na, not available; Neutropenia (%), % of patients treated; OR, overall response; OS, overall survival; PFS(m), progression free survival (months); RCT, randomized control trial; sc, subcutaneous.