Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia
N = 509
- Population
- Previously untreated patients with chronic lymphocytic leukemia.
- Design
- Randomised comparison, 1990 to 1994, of fludarabine 25 mg/m2 intravenously daily for 5 days every 28 days, chlorambucil 40 mg/m2 orally every 28 days, or fludarabine 20 mg/m2 per day for 5 days plus chlorambucil 20 mg/m2 every 28 days; patients with an additional response at each monthly evaluation continued for up to 12 cycles. Arm sizes shown (170 and 181) are the numbers treated as stated in the abstract; 509 were randomised. Assignment to the combination arm was stopped after a planned interim analysis (excessive toxicity; response rate not better than fludarabine alone). No NCT number is given in the PubMed record and none was located on ClinicalTrials.gov.
- Arms
- Fludarabine (experimental, n = 170): Fludarabine 25 mg/m2 daily for 5 days every 28 days, up to 12 cycles
- Chlorambucil (control, n = 181): Chlorambucil 40 mg/m2 orally every 28 days, up to 12 cycles
- Fludarabine plus chlorambucil (experimental): Fludarabine 20 mg/m2 per day for 5 days plus chlorambucil 20 mg/m2 every 28 days
- People
- Rai KR
Δ CR rate+16 pointsΔ median PFS+6 monthsΔ median OS+10 months
Show the numbers
| Endpoint | Analysis | Fludarabine / Fludarabine plus chlorambucil | Chlorambucil | Effect |
|---|---|---|---|---|
| CR ratePatients treated: 170 with fludarabine, 181 with chlorambucil | primaryRai 2000 | 20% | 4% | P<0.001Partial remission 43% with fludarabine vs 33% with chlorambucil (P<0.001). |
| PFSAnalysis population not stated in the abstract (response rates are reported for the 170 and 181 patients treated) | primaryRai 2000 | median 20 months | median 14 months | P<0.001Median duration of remission 25 months with fludarabine vs 14 months with chlorambucil (P<0.001). |
| OSAnalysis population not stated in the abstract (groups: fludarabine, chlorambucil and the combination arm) | primaryRai 2000 | median 66 months | median 56 months | The abstract states that the fludarabine overall survival was not significantly different from the other two groups; no p-value is given there. |
| Endpoint | Analysis | Fludarabine / Fludarabine plus chlorambucil | Chlorambucil | Effect |
|---|---|---|---|---|
| CR ratePatients treated: 170 with fludarabine, 181 with chlorambucil | primaryRai 2000 | 20% | 4% | P<0.001Partial remission 43% with fludarabine vs 33% with chlorambucil (P<0.001). |
| PFSAnalysis population not stated in the abstract (response rates are reported for the 170 and 181 patients treated) | primaryRai 2000 | median 20 months | median 14 months | P<0.001Median duration of remission 25 months with fludarabine vs 14 months with chlorambucil (P<0.001). |
| OSAnalysis population not stated in the abstract (groups: fludarabine, chlorambucil and the combination arm) | primaryRai 2000 | median 66 months | median 56 months | The abstract states that the fludarabine overall survival was not significantly different from the other two groups; no p-value is given there. |
- Fludarabine (experimental)
- Chlorambucil (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Fludarabine | Chlorambucil |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 13 | 63.7% | 52.5% |
| 25 | 42.0% | 29.0% |
| 38 | 26.8% | 15.2% |
| 50 | 17.7% | 8.4% |
- Fludarabine (experimental)
- Chlorambucil (control)
- Fludarabine plus chlorambucil (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Fludarabine | Chlorambucil | Fludarabine plus chlorambucil |
|---|---|---|---|
| 0 | 100.0% | 100.0% | 100.0% |
| 41 | 65.0% | 60.2% | 59.6% |
| 83 | 41.8% | 35.8% | 35.1% |
| 124 | 27.2% | 21.5% | 21.0% |
| 165 | 17.7% | 13.0% | 12.5% |