my personal edition > leukaemias > news


  E-Mail this DGDispatch to a colleague

DGDispatch

Rituximab Adds to Efficacy of Fludarabine/Cyclophosphamide in Chronic Lymphocytic Leukaemia: Presented at NHL

By Chris Berrie

PRAGUE, CZECH REPUBLIC -- September 14, 2004 -- Fludarabine/cyclophosphamide (FC) chemotherapy appears to have significantly improved clinical outcomes when combined with the addition of rituximab (FCR) for first-line treatment of progressive and advanced chronic lymphocytic leukaemia (CLL), according to an analysis presented here September 11^th at The Role of Immunotherapy in NHL: Optimising Treatment Outcomes, sponsored by Roche.

"We decided to do these univariate and multivariate analyses of these sequential trials as we were impressed with the response rate and that time to progression was much higher in the combination FCR as compared with FC and fludarabine plus or minus prednisone," said Michael Keating, MD, professor of medicine, haematology, MD Anderson Cancer Center, Houston, Texas, United States.

These analyses also allowed adjustments not only to highlight significant prognostic factors, but also for the determination of the characteristics associated with both response and survival in each subset of patients.

The data in each of the treatment groups were from previously untreated patients. From 1986 to 1993, the standard treatment was single-agent fludarabine 30 mg/m² for 5 days every 28 days prior to the addition of prednisone 30 mg/m²/day to this 5-day treatment (FP). From November 1993, patients received fludarabine 30 mg/m² for 3 days combined with mitoxantrone 10 mg/m² on day 1 (FM) or cyclophosphamide 300 mg/m² (FC). Finally, from July 1999, fludarabine 25 mg/m² and cyclophosphamide 250 mg/m² on days 1-3 on days 2-4 in course 1 were combined with rituximab on day 1 375 mg/m² on course 1 and 500 mg/m² on courses 2-6 (FCR). All cycles were given every 28 days for 6 cycles.

Responses by treatment group demonstrated complete remission (CR) and overall response (OR) rates with fludarabine/FP (n = 193) were 31%/84%; with FM/FC (n = 135) they were 32%/86%; and with FCR (n = 224) they were 71%/95%. The FCR CR was significantly different to the other treatments (P <.001).

The univariate analysis showed that Rai and Binet stages (P =.004), age (P =.002), hemoglobin (P =.003), platelets (P =.003), serum beta-2 microglobulin (P =.002), and bone marrow cellularity (P =.001) were all associated with the probability of CR. Similarly, and as might be expected, the pretreatment characteristics associated with survival by univariate analysis paralleled those for CR and OR, Dr. Keating said.

After multivariate analysis, it was seen that beta-2 microglobulin (P <.001) and marrow cellularity (P <.05) were the only characteristics associated with CR. The FCR protocol was the dominant characteristic, and it was the single characteristic most strongly associated with overall response.

For duration of remission, the multivariate analysis showed a rank order of FCR, National Cancer Institute Working Group (NCIWG) response and white blood cells. At the same level, survival was most closely associated with treatment group (eg, FC/FM vs FCR; P =.002), age (eg, 55-64 vs 65 or older; P =.001), hemoglobin, performance status, beta-2 microglobulin (eg, 3.1-4.0 vs 4 or greater; P =.001), and NCIWG response.

"The next stage is, I think, going to be focussing on particular subsets now that we can identify subsets of CLL more efficiently by looking at the mutation status, and Zap70 and p53 mutations, etc.," Dr. Keating said. Thus, it should become possible to determine what prognostic factors to use to direct the therapy for specific subgroups of the general pool of CLL patients, he added.


[Presentation title: Chemotherapy With Fludarabine, Cyclophosphamide and Rituximab Improves Complete Response, Remission Duration, and Survival as Initial Therapy of Chronic Lymphocytic Leukaemia. Abstract 555]

E-Mail this DGDispatch to a colleague

To print, use this version