Bendamustine treatment demonstrated better overall response rate and PFS
than chlorambucil treatment in previously untreated patients with
advanced CLL.
Researchers conducted a phase-3 multicenter study and randomly assigned
319 patients IV bendamustine (Treanda, Cephalon) 100 mg/m2 per day
on days one to two, or chlorambucil (Leukeran, Smithkline Beecham) 0.8 mg/kg
orally on days one and 15. Every four weeks, treatment cycles were repeated for
a maximum of six cycles.
Overall, 68% of 162 patients in the bendamustine group and 31% of 157
patients in the chlorambucil group had complete or partial response
(P<.0001).
More patients treated with bendamustine (31%) had complete response vs.
patients treated with chlorambucil (2%). Additionally, 11% of patients in the
bendamustine group had nodular partial response compared with 3% of patients in
the chlorambucil group.
Among patients with Binet stage C disease, 20% treated with bendamustine
demonstrated complete response, whereas no patients treated with chlorambucil
did.
The bendamustine group demonstrated a higher median PFS rate (21.6
months) compared with the chlorambucil group (8.3 months; P<.0001);
this difference was observed in patients with both Binet stage B and C disease.
The median duration of response was 21.8 months in patients treated with
bendamustine and only eight months in patients treated with chlorambucil.
Grade-3 or -4 severe infections were noted in 8% of patients in the
bendamustine group and in 3% of patients in the chlorambucil group.
Knauf WU. J Clin Oncol.
2009;doi:10.1200/JCO.2008.20.8389.
Those who treat patients with CLL are happy to see the publication in
JCO of the detailed results of the large, multi-institutional and multinational
randomized study comparing bendamustine and chlorambucil . We had known of
these results when they were presented at the annual meeting of the American
Society of Hematology some time ago, and then this drug also had received
approval from the FDA, but their publication in a peer-reviewed professional
journal such as JCO, gives the data a certain level of legitimacy.
CLL patients and their treating hematologists-oncologists are happy to
have available yet another drug with known and proven efficacy. In CLL, we are
somewhat desperate to have more choices because the natural history of this
disease is such that patients tend to run out of options. Bendamustine will
find increasing usage with the passage of time because doctors are still on a
learning curve and first-hand witness its efficacy and toxicity profiles, and,
thus, develop some familiarity with this drug.
In the near future additional work should be done to determine how best
to classify bendamustine: Is it only an alkylating agent or does it also have
some elements of purine antimetabolites? Resolution of this question will help
us better understand the mechanism of its actions. At the clinical level,
another natural and important question to answer in the future is whether its
activity can be significantly enhanced by using bendamustine in combination
with monoclonal antibodies such as rituximab, ofatumumab and such or with other
chemotherapy drugs which work through different mechanisms.
– Kanti R. Rai, MD
Chief, Division of Hematology-Oncology,
Long Island
Jewish Medical Center, New Hyde Park, NY
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