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BioOncology Watch Timely Information for Practicing
Physicians |
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may
2003 NON-HODGKIN'S LYMPHOMA (NHL) Safety profile of Zevalin®. Zevalin (90Y ibritumomab tiuxetan; IDEC
Pharmaceuticals) is a 90Y-labeled anti-CD20 antibody. Thomas Witzig and colleagues presented
safety data obtained from 5 studies (N = 349) of Zevalin treatment of
patients with relapsed or refractory low-grade, follicular, or transformed
CD20-positive B-cell NHL. Patients
were administered rituximab on Days 1 and 8 and either 0.4 mCi/kg (patients
with platelet counts ≥150,000/mL) or 0.3 mCi/kg (patients with platelet counts
between 100,000 and 149,000/mL) of
Zevalin on Day 8 (maximum dose, 32 mCi).
Grade 3 and grade 4 (National Cancer Institute's Common Toxicity
Criteria) neutropenia, thrombocytopenia, and anemia developed in 30% and 30%,
53% and 10%, and 13% and 4% of patients, respectively. Patients with bone marrow involvement with
lymphoma (n = 146 [42%]) had a greater incidence of grade 4 neutropenia (p =
0.001), thrombocytopenia (p = 0.013), and anemia (p = 0.040). Nadir counts occurred at week 7-9 and
lasted 1-4 weeks. Seven percent of
patients were hospitalized with infection and 2% of patients had grade 3 or 4
bleeding adverse events. Rituximab infusion-related
toxicities were typically grade 1 or 2.
No significant organ toxicity was observed. Myelodysplasia or acute myelogenous
leukemia was reported in 5 patients (1%) from PANCREATIC CANCER Phase II study of the farnesyltransferase inhibitor
R115777. Steven Cohen and associates
conducted a study in which 20 patients with previously untreated measurable
metastatic pancreatic cancer were administered 300 mg of R115777, a selective
inhibitor of farnesyltransferase, orally every 12 hours for 21 of 28
days. R115777 had previously
demonstrated activity against pancreatic cancer cell lines and xenograft
models. Farnesyltransferase activity
in peripheral-blood mononuclear cells of patients was found to decrease by a
mean of 49.8% ± 9.8% 4 hours after the initial dose of R115777. Despite this inhibition of
farnesyltransferase activity, no objective responses were achieved. The median time to progression was 4.9
weeks and the median overall survival time was 19.7 weeks. Grade 3 or 4 toxicities included
transaminase elevation, anemia, neutropenia, thrombocytopenia, fatigue,
nausea/vomiting, rash, and anorexia and 9 (45%) patients required dose
reductions of R115777 during the first cycle.
This study did not demonstrate single-agent R115777 clinical activity
against previously untreated metastatic pancreatic cancer. (Cohen SJ, et al. J Clin Oncol 2003;21:1301-1306) RENAL CELL
CARCINOMA (RCC) Adjuvant interferon alfa therapy. Edward Messing and others performed a phase
III study in which 283 patients with locally and/or regionally extensive RCC
who had undergone nephrectomy and lymphadenectomy were randomized to adjuvant
interferon alfa-NL (Wellferon; Burroughs-Wellcome) therapy or observation. Interferon alfa-NL was administered by
intramuscular injection daily for 5 days every 3 weeks for up to 12 cycles by
the following schedule: 3 million U/m2 on Day 1; 5 million U/m2
on Day 2, and 20 million U/m2 on Days 3, 4, and 5. With a median
follow-up of 10.4 years, the median recurrence-free survival was 3.0 years
for the observation group compared to 2.2 years for interferon-treated
patients (p = 0.33). The median
overall survival times were 7.4 years and 5.1 years for the observation and
interferon groups, respectively (p = 0.09).
Grade 4 toxicities (neutropenia, myalgias, fatigue, depression, and
neurologic untoward effects) occurred in 11.4% of interferon-treated
patients. These results show that
adjuvant interferon alfa-NL treatment following nephrectomy did not provide
clinical benefit for patients with locally advanced RCC. (Messing EM, et al. J Clin Oncol 2003;21:1214-1222) MYELOFIBROSIS WITH MYELOID METAPLASIA (MMM) Combination thalidomide plus prednisone therapy. MMM is a clonal hematopoietic stem cell disorder
characterized by progressive anemia, leukoerythroblastosis, splenomegaly,
progression to acute leukemia, and premature death. The lack of effective therapy for this
disease has stimulated study of the pathogenetic mechanisms of MMM. The demonstration of progressive
neoangiogenesis in MMM led to investigation of the antiangiogenic agent
thalidomide. Single-agent thalidomide
at doses >100 mg/day has been associated with an amelioration of the
anemia of MMM in approximately 20% of cases, but is poorly tolerated. Ruben Mesa and coworkers at the Mayo Clinic
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