Targeted Therapies

Formerly BioOncology Watch

www.tgt-therapies.com

FEBRUARY 2005

CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

Rituximab plus fludarabine.  John Byrd and colleagues report a retrospective analysis comparing treatment outcomes of previously untreated CLL patients enrolled into 2 multicenter Cancer and Leukemia Group B (CALGB) trials and treated with fludarabine plus rituximab (CALGB 9712) or fludarabine alone (CALGB 9011).  The eligibility criteria of these 2 studies were virtually identical.  Patients enrolled into study CALGB 9712 were randomized to receive rituximab either concurrently or sequentially with fludarabine therapy. Progression free survival (PFS) and overall survival (OS) were similar for each treatment group.  Patients enrolled into CALGB 9011 were randomized to receive fludarabine, chlorambucil, or fludarabine plus chlorambucil; data from the fludarabine-only group were utilized in the current analysis.  PFS and OS were greater in the fludarabine plus rituximab group than in the fludarabine-only group (p < 0.0001 and p = 0.0006, respectively).  The 2-year PFS probabilities were 0.67 versus 0.45, and the 2-year OS probabilities were 0.93 versus 0.81.  The safety profiles were similar between the 2 groups.  Possible differences between the 2 patient populations in this retrospective analysis could confound the data. Thus, a prospective, randomized trial is required to confirm these results.  (Byrd JC, et al. Blood 2005;105:49-53)

 

NON-HODGKIN'S LYMPHOMA (NHL)

Long-term follow-up after treatment with rituximab plus CHOP (R-CHOP).  Myron Czuczman and others present updated outcome data, after a 9-year follow-up, on 38 patients with low-grade and follicular NHL treated in the original phase II trial investigating R-CHOP. Of the 38 patients, 9 (24%) patients had received prior chemotherapy.  Patients received 6 cycles of CHOP chemotherapy and 6 infusions of rituximab during the treatment period of the study.  The overall response rate was 100%, and 87% of patients achieved a complete response or an unconfirmed complete response.  The median duration of response was 83.5 months; the median time to disease progression was 82.3 months.  Among 8 patients who had bcl-2 positive disease at baseline, 7 achieved molecular remission (molecular remission was sustained in 3 cases).  This analysis shows that R-CHOP therapy was associated with durable responses in patients with relapsed or newly diagnosed indolent NHL.  (Czuczman MS, et al. J Clin Oncol 2004;22:4711-4716)

 

Clinical outcome after idiotype vaccination.  Wen-Kai Weng et al. analyzed 136 patients with follicular lymphoma who had received immunoglobulin idiotype (Id) vaccination.  All patients had been treated with induction chemotherapy to achieve maximum clinical response prior to vaccination.  Patients who mounted anti-Id humoral immune responses were observed to have longer median PFS times than those who did not (8.21 vs. 3.38 years; p = 0.018).  In addition, the presence of the immunoglobulin G Fc receptor (FcγR) IIIa polymorphism (158 valine/valine genotype) was found to predict for longer PFS.  The results of this study indicate that antibodies induced against a tumor antigen are beneficial.  Moreover, cells bearing FcγR can mediate an antitumor effect by killing antibody-coated tumor cells.  (Weng W-K, et al. J Clin Oncol 2004;22:4717-4724)

 

ACUTE PROMYELOCYTIC LEUKEMIA (APL)

Results of all-trans retinoic acid (ATRA) and anthracycline monochemotherapy in the elderly. The marked improve-ments in clinical outcomes for patients with APL resulting from the combination of ATRA and anthracycline chemotherapy have been less dramatic for the elderly.  Miguel Sanz and coworkers report the findings from 104 consecutive patients with newly diagnosed APL, 60 years or older, who were enrolled into 2 successive PETHEMA Group studies. These studies involved induction therapy with ATRA plus idarubicin, consolidation with anthracycline monochemotherapy with or without ATRA, and maintenance therapy with ATRA plus low-dose chemotherapy. Induction therapy produced complete remission in 87 (84%) patients. Five patients relapsed and 7 patients died during remission. The leukemia-free survival rate at 6 years was 91%. This analysis shows that induction and consolidation treatments with ATRA and anthracycline monochemotherapy have high antileukemic efficacy and are well tolerated in elderly patients with APL. (Sanz MA, et al. Blood 2004;104:3490-3493)

 

METASTATIC BREAST CANCER

Phase III study of oral marimastat.  Joseph Sparano and colleagues from the Eastern Cooperative Oncology Group (ECOG) conducted a double-blind, multicenter phase III study (ECOG E2196) in which 179 patients with metastatic breast cancer who had responsive or stable disease after first-line doxorubicin- and/or taxane-containing chemotherapy were randomized to receive the matrix metalloproteinase inhibitor marimastat (10 mg bid orally) or placebo.  No differences in PFS or OS were observed between the 2 treatment groups (p = 0.16 and 0.86, respectively).  Marimastat-treated patients who developed grade 2 or 3 musculoskeletal toxicity had a shorter median OS than did patients who had grade 0 or 1 musculoskeletal toxicity (22.5 months vs. 28.2 months; p = 0.04). These data demonstrated that therapy with marimastat after first-line chemotherapy for patients with metastatic breast cancer did not prolong PFS or OS compared with placebo treatments.  (Sparano JA, et al. J Clin Oncol 2004;22:4683-4690)

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