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R115777 Has Significant Activity in CML and Myelofibrosis

R115777 Has Significant Activity in CML and Myelofibrosis

HOUSTON—The farnesyl transferase inhibitor R115777 (tipifarnib, also
known as Zarnestra) produced an overall response rate of 33% in patients
with chronic myelogenous leukemia (CML) and decreased splenomegaly in most
patients with myelofibrosis, but was not effective in multiple myeloma,
reported Deborah Thomas, MD, at the 43rd Annual Meeting of the American
Society of Hematology. Dr. Thomas is assistant professor in the Department
of Leukemia at The University of Texas M. D. Anderson Cancer Center in

Dr. Thomas reported data on 36 patients treated with R115777. This
included 21 patients with CML (10 in chronic phase, 5 in accelerated phase,
6 in blast phase), 10 patients with multiple myeloma, and 5 patients with
myelofibrosis. All patients with accelerated or blast phase CML had
previously received imatinib mesylate (Gleevec, also known as STI571), as
had four of the patients with chronic phase CML.

For patients with CML, the median age was 54 years, the median time from
diagnosis was 20 months, and the median number of prior therapies was 3
(range: 2 to 5). Three of 13 patients for whom ras mutation results are
available had mutations of N-ras (n = 1) or K-ras (n = 2).

Patients received oral R115777, 600 mg bid for 28 days every 6 weeks. The
doses were adjusted for myelosuppression and/or nonhematologic toxicity.

Response Data

Dr. Thomas said that six CML patients in chronic phase had a complete (n
= 5) or partial (n = 1) hematologic response. Three of the patients with
chronic phase CML achieved a minor cytogenetic response. One patient in
accelerated phase (clonal evolution) had a complete hematologic response and
minor cytogenetic response. None of the six patients in blast phase

Eight patients with myelofibrosis were treated after a median time from
diagnosis of 18 months (range: 11-32). They had received a median of 3
prior therapies (range: 1-5). Six of eight had a reduction in spleen size
(more than 50% in two patients), from a median of 13 cm below costal margin
to a median of 9 cm. One patient had hepatomegaly and had a modest reduction
(15 to 12 cm). One patient was taken off study after 2 months because of
skin toxicity, and one transformed to acute myelogenous leukemia 6 weeks
after the start of therapy.


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