Commentary on Abstract #418

Publication
Article
OncologyONCOLOGY Vol 13 No 3
Volume 13
Issue 3

The currently available nucleoside analogs, such as fludarabine, have revolutionized the approach to the treatment of indolent lymphoid malignancies. Fludarabine is the most effective agent for the treatment of chronic lymphocytic leukemia (CLL) and also exhibits major activity in low-grade NHL. Despite the impressive rates of complete remissions, patients with these malignancies remain incurable, and new agents are needed.

The currently available nucleoside analogs, such as fludarabine, have revolutionized the approach to the treatment of indolent lymphoid malignancies. Fludarabine is the most effective agent for the treatment of chronic lymphocytic leukemia (CLL) and also exhibits major activity in low-grade NHL. Despite the impressive rates of complete remissions, patients with these malignancies remain incurable, and new agents are needed.

Several approaches are under study to achieve higher response rates and more durable remissions. A major focus has been on identifying new agents with unique mechanisms of action. One of the most exciting of the new drugs is compound 506U, the prodrug of arabinosylguanine (ara-G). This agent has demonstrated impressive activity in a variety of T-cell malignancies, such as acute lymphocytic leukemia (ALL) and T-cell lymphoblastic leukemia (T-LBL), with complete remissions occurring even in patients who have not responded to bone marrow transplantation (Kurtzberg et al: J Clin Oncol 14:1750 [abstract 2022], 1996).

Although compound 506U is believed to act specifically against T-cell disorders, responses have been observed in more than 30% of patients with B-cell CLL who did not respond to fludarabine and an alkylating agent. A national trial is underway to confirm these observations. The major toxicities of this agent include immunosuppression and neurologic effects, which appear to be schedule-dependent.

Gandhi et al (abstract #418) have demonstrated that intracellular concentrations of compound 506U correlate well with response to therapy (Gandhi et al: J Clin Oncol 17:3607-3615, 1998) Such studies should help identify patients most likely to benefit from this drug.

A national trial is currently evaluating compound 506U in patients with CLL who have not responded to both fludarabine and an alkylating agent. Additional trials are studying the drug in children and adults with T-cell ALL and lymphoblastic lymphoma.Future trials will study compound 506U in peripheral T-cell NHL and cutaneous T-cell NHL, as well as in indolent lymphomas.

Articles in this issue

WHO Declares Lymphatic Mapping to Be the Standard of Care for Melanoma
Rituximab: Phase II Retreatment Study in Patients With Low-Grade or Follicular Non-Hodgkin’s Lymphoma
Response Criteria for NHL: Importance of “Normal” Lymph Node Size and Correlations With Response
Chemotherapy Plus Radiation Improves Survival in Patients With Cervical Cancer
A Randomized Trial of Fludarabine, Mitoxantrone (FM) Versus Doxorubicin, Cyclophosphamide, Vindesine, Prednisone (CHEP) as First Line Treatment in Patients With Advanced Low-Grade Non-Hodgkin's Lymphoma: A Multicenter Study by GOELAMS Group
Navelbine Increased Elderly Lung Cancer Patients’ Survival
Fludarabine Versus Conventional CVP Chemotherapy in Newly C Diagnosed Patients With Stages III and IV Low-Grade Malignant Non-Hodgkin’s Lymphoma: Preliminary Results From a Prospective, Randomized Phase III Clinical Trial in 381 Patients
Multicenter, Phase III Study of Iodine-131 Tositumomab (Anti-B1 Antibody) for Chemotherapy-Refractory Low-Grade or Transformed Low-Grade Non-Hodgkin’s Lymphoma
T-Cell–Depleted Allogeneic Bone Marrow Transplant From HLA-Matched Sibling Donors for Non-Hodgkin’s Lymphoma
Consensus Statement on Prevention and Early Diagnosis of Lung Cancer
In Vivo Purging and Adjuvant Immunotherapy With Rituximab During PBSC Transplant For NHL
Fludarabine and Cyclophosphamide: A Highly Active and Well-Tolerated Regimen for Patients With Previously Untreated Indolent Lymphomas
Campath-1H Monoclonal Antibody in Therapy for Advanced Low-Grade Non-Hodgkin’s Lymphomas: A Phase II Study
AIDS Drugs Effective Against Most Common HIV Strain
Rituximab Therapy in Previously Treated Waldenström’s Macroglobulinemia: Preliminary Evidence of Activity
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