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BioOncology Watch Timely Information for Practicing
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december 2002 RITUXIMAB Indolent non-Hodgkin's lymphoma (NHL). John Hainsworth and associates
administered rituximab 375 mg/m2 weekly for 4 weeks to patients
with previously untreated indolent NHL.
Patients with objective response or stable disease received up to 4
more courses of rituximab at 6-month intervals. The minimum follow-up was 24 months and 60 patients were
evaluable. Seventy-three percent of
patients achieved a response (37% CRs) and the response rate was similar for
patients with follicular and small lymphocytic subtypes (76% vs. 70%). The median actuarial progression-free
survival was 34 months. No cumulative
toxicities were associated with multiple rituximab courses. These findings, while promising, require
confirmation in randomized trials in patients with previously untreated
indolent NHL. (Hainsworth JD, et al. J Clin Oncol 2002;20:4261-4267) Acquired factor VIII inhibitors. Adrian Wiestner and coworkers utilized weekly rituximab
infusions (375 mg/m2) to treat 4 consecutive patients with
acquired factor VIII inhibitors because this anti-CD20 monoclonal antibody
rapidly clears circulating B cells.
Rituximab therapy was associated with a decrease in inhibitor titers
and clinical improvement. All
patients had remained in remission for 7+ to 12+ months. This report is additional evidence that
rituximab effectively ameliorates immune disorders resulting from
autoantibody formation. (Wiestner A, et al. Blood 2002;100:3426-3428) HODGKIN'S DISEASE Bispecific molecule (H22xKi-4).
H22xKi-4 (Medarex) is a bispecific molecule consisting of F(ab)
fragments derived from murine anti CD30 (Ki-4) and humanized anti-CD64 (H22)
monoclonal antibodies. Peter
Borchmann et al. performed a phase I study of H22xKi-4 treatments in 10
patients with CD30+ Hodgkin's lymphoma (HL).
The anti-CD64 portion of the molecule serves to trigger cytotoxic
effector cells. H22xKi-4 was
intravenously administered on Days 1, 3, 5, and 7. Doses up to 20 mg/m2/day
were tolerated well with transient mild infusion-related side effects. The elimination half-life (11.1 hours)
resulted in significant accumulation of H22xKi-4. Four patients achieved a response (1 CR; 3 PRs) and 4 patients
had stable disease. These findings
warrant further investigation of this novel agent. (Borchmann P, et al. Blood 2002;100:3101-3107) MULTIPLE MYELOMA (MM) Immunomodulatory drugs. Thalidomide has been shown to overcome drug resistance in
relapsed and refractory MM. S.
Vincent Rajkumar and colleagues at the Mayo Clinic (Rochester, MN) report the
use of thalidomide (200 mg/day), in combination with high-dose dexamethasone,
to treat patients with newly diagnosed MM (n=50). Thirty-two patients (64%) achieved a response and stem-cell
collections were accomplished without difficulties. In another study, K. Dredge et al. report that novel
thalidomide analogues display anti-angiogenic activity and are significantly
more potent than thalidomide. Also,
Paul Richardson et al. at the Dana Farber Cancer Institute (Boston, MA)
conducted Phase I study in relapsed or refractory MM patients with one of
these potent immunomodulatory derivatives (IMiDs), CC-5013 (REVIMID; Celgene
Corp.), and report that treatment was well tolerated and associated with a
high rate of clinical benefit (71%).
These findings indicate that thalidomide and the IMiD compounds are
associated with high rates of response and are potentially effective
therapies against MM. (Rajkumar SV,
et al. J Clin Oncol
2002;20:4319-4323; Dredge K, et al. Br
J Cancer 2002;87:1166-1172; Richardson PG, et al. Blood 2002;100:3063-3067) EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) INHIBITION ZD1839 (Iressa). Alan
Wakeling and coworkers report that daily oral ZD1839 inhibited tumor growth
in a dose-dependent manner in mice bearing human tumor-derived
xenografts. Long-term (>3 months)
ZD1839 treatment of mice induced regression of established tumors without the
development of drug resistance. A
phase I study of daily oral ZD1839 administered to patients with refractory
solid tumors conducted by J. Baselga et al. identified the dose-limiting
toxicities to be grade 3 diarrhea and somnolence. Pharmacokinetic studies showed that steady-state exposure was
achieved by Day 7. Nineteen patients
had stable disease for ³3
months. This article includes
references that describe in detail the preclinical information for
ZD1839. These findings for this novel
anticancer agent warrant further investigation. (Wakeling AE, et al. Cancer
Res 2002;62:5749-5754; Baselga J, et al. J Clin Oncol 2002;20:4292-4302) MALIGNANT MELANOMA Vaccination therapy. Filiberto Belli and colleagues immunized metastatic melanoma
patients (n=42) with autologous tumor-derived heat shock protein gp96-peptide
complexes (HSPPC-96, Oncophage: Antigenics, Inc.). Enzyme-linked immunospot assays detected increased
melanoma-specific T-cell activity in 11 of 23 evaluable patients. Among 28
patients with measurable disease, 2 patients achieved a durable complete
response and 3 patients had stable disease.
In a second study, Peter Hershey et al. conducted a multicenter study
in which 700 patients with high-risk melanoma were randomized to receive a
vaccine prepared from vaccinia melanoma cell lysate (n=353) or no
immunotherapy (n=347). After a median
follow-up time of 8 years, trends towards improved median relapse-free
survival (83 months vs. 43 months; p=0.17) and overall survival (151 months
vs. 88 months; p=0.068) were realized.
These vaccine studies demonstrate a potentially effective therapy in
both the metastatic and adjuvant settings for patients with malignant
melanoma. (Belli F, et al. J Clin Oncol 2002;20:4169-4180;
Hershey P, et al. J Clin Oncol 2002;20:4181-4190)
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