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Fludarabine Combos Showing Efficacy in Lymphomas

Fludarabine Combos Showing Efficacy in Lymphomas

LUGANO, Switzerland—For low-grade lymphomas, fludarabine (Fludara)-based
combination therapy may have greater efficacy than single-agent flu-darabine,
especially when a monoclonal antibody is part of the combination, a series of
recent European investigations suggest. The investigations, presented at the
Eighth International Conference on Malignant Lymphoma (ICML), show that
various combination therapies hold promise, although a lack of coordination
among non-US study groups has hampered progress somewhat.

"It is a little bit disappointing . . . that there are still so many
patients being entered into so many different trials," said Emili Montserrat,
MD, of the University of Barcelona. "We could work much more quickly and have
results faster by establishing some kind of international cooperation."

Not Yet Standard Practice

Dr. Montserrat, who moderated a standing-room-only session on fludara-bine
combination therapy, stressed that none of the combinations under
investigation are yet part of standard clinical practice and should not be
used except in clinical trials. Nonetheless, the rationale for trying such
combinations is backed by preclinical data showing synergistic cytotoxicity
against malignant cells. Furthermore, fludarabine combinations do seem
superior to fludarabine alone, at least when compared with historical data,
experts said.

"The phase II combination studies appear to be superior, particularly when
you add in monoclonal antibodies," said John Seymour, MB, BS, FRACP, of the
Peter MacCallum Cancer Institute, Melbourne, Australia. "They have the
highest overall response rate and, particularly, an extremely high molecular
response rate, which appears to be the best surrogate predictive factor for
long-term disease control."

Adding Rituximab

The field is changing rapidly. Dr. Sey-mour said that his institution’s
current standard treatment is a combination of fludarabine, cyclophosphamide,
and rituximab (Rituxan). That combination, he said, is based mainly on
interim analyses and sometimes phase II data, rather than randomized phase
III studies.

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