LUGANO, SwitzerlandFor 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."
The field is changing rapidly. Dr. Sey-mour said that his institution’s current standard treatment is a combination of fludarabine, cyclophosphamide(Drug information on 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.