FCR (fludarabine, cyclophosphamide,
rituximab) has produced the
highest complete response (CR) rate
seen thus far in first-line treatment of
chronic lymphocytic leukemia (CLL),
according to investigator Michael J.
Keating, MD. The FCR regimen,
which is well tolerated, also results in
molecular remissions in a "significant
number" of complete responders, said
Dr. Keating, professor of medicine,
M.D. Anderson Cancer Center.
"I think we now have an outpatient
regimen that can accomplish
PCR [polymerase chain reaction]
negativity to a level that was formerly
only achievable with various
transplant procedures," Dr. Keating
said. "It will be intriguing to follow
these patients and see how durable
these responses are."
The study, which included 135 patients
with CLL who received six cycles
of FCR, achieved a complete response
rate of 67% (90 patients), Dr.
Keating reported at the 8th International
Conference on Malignant
Lymphoma (ICML abstract 008). By
comparison, front-line fludarabine
(Fludara), in previous investigations,
has resulted in a 35% complete remission
rate, while adding cyclophosphamide
to fludarabine increases the
CR rate to 43%.
The FCR regimen is an infusion
of rituximab (Rituxan) at a conventional
dose (375 mg/m2) on the first
day of the first cycle, with fludarabine
and cyclophosphamide given on days
2, 3, and 4. In subsequent cycles,
rituximab is given at a higher dose
(500 mg/m2) on day 1, along with
the 3-day fludarabine/cyclophosphamide
couplet. Cycles are repeated every
4 weeks for a total of six cycles.
The median patient age was 57
years, or somewhat lower than in
previous studies of first-line treatment
for CLL. Dr. Keating attributes
this to the "Internet phenomenon"-
younger patients seeking out
more aggressive therapies.
The treatment was well tolerated,
with 74% of patients completing
six cycles, and only 4% completing
less than three cycles.
Overall Response Rate
The overall response rate was
95%, including 67% complete remissions,
14% nodular partial remissions,
and 14% partial remissions.
Early death occurred in 2
patients (1%). "Although this is a
very aggressive approach, the early
death rate was actually quite low,"
Dr. Keating said. With a median follow-
up of 27 months, 125 of the
135 patients are still alive.
Phase II Trial of ISF154 for Treatment of CLL
SAN DIEGO-Tragen Pharmaceuticals has initiated a phase II clinical
trial of its lead product, ISF154, in the treatment of patients with chronic
lymphocytic leukemia (CLL). ISF154 is designed to activate dormant
leukemia B-cells and rally T-cells to attack blood- and tissue-based
leukemia cells, the company said in a press release.
Investigators will administer ISF-154 to 40 patients in two cohorts: 20
patients who have failed chemotherapy will receive up to 10 doses of
ISF154 over 20 weeks; 20 patients with advanced disease who have
declined chemotherapy will receive up to 10 doses of ISF154 as
Complete response rate did not
vary much according to Rai stage
(69% for stage 0-II and 52% for stage
III-IV). However, the CR rate was
66% for patients under 70 years of
age vs 33% for patients over 70, and
low beta-2-microglobulin levels
were a "very powerful predictive factor"
in favor of complete response.
Molecular remission (as shown
by PCR negativity for IgH) was seen
in 58% of complete responders tested
(33 of 57 patients). Of 26 patients
tested again after 6 months,
18 (69%) remained negative, and 5
of 6 patients tested again at 12
months remained negative.
Toxicity associated with
rituximab infusion included fever
and chills with the first dose for 45
patients; a few patients had hypotension,
nausea, or dyspnea, although
all of these toxicities were uncommon
in later cycles. Hematologic toxicities
included neutropenia (31% of
cycles) and grade 3-4 thrombocytopenia
(6% of cycles). Major infections
occurred in 2% of cycles.