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BioOncology Watch Timely Information for Practicing
Physicians |
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october 2002 COLON CANCER Edrecolomab adjuvant therapy does
not provide clinical benefit.
Cornelis Punt et al. conducted a large phase III trial in which 2,761
patients with resected a stage III colon cancer were randomized to receive
approximately 6 months (6 cycles) of either fluorouracil-folinic acid (Mayo
Clinic regimen) alone, or edrecolomab alone (administered intravenously once
monthly), or combination edrecolomab plus fluorouracil-folinic acid. After a median follow-up of 26 months
(range, 20-36 months), the 3-year survival (74.7% vs. 76.1%) and disease-free
survival (63.8% vs. 65.5%) rates achieved in the combination therapy and the
fluorouracil-folinic acid treatment groups were similar (p=0.52 and 0.22,
respectively). In addition, the
3-year survival and disease-free survival rates of the edrecolomab-alone
treatment group were less than those for patients who received
fluorouracil-folinic acid alone (p=0.05 and <0.0001, respectively). Hypersensitivity reactions occurred in 25%
of patients receiving edrecolomab (4% discontinued therapy), however the
addition of edrecolomab to chemotherapy did not increase the incidence of
neutropenia, diarrhea, or mucositis.
This large phase III experience demonstrated that edrecolomab therapy
did not enhance the clinical benefit of standard adjuvant chemotherapy for
patients with Stage III colon cancer. (Punt CJA, et al. Lancet 2002;360:671-677) POST-TRANSPLANTATION
LYMPHOPROLIFERATIVE DISEASE (PTLD) Effectiveness of partly
HLA-matched allogeneic cytotoxic lymphocytes (CTLs). In a pilot study, Tanzina Haque and
colleagues administered 1 to 6 infusions of partly HLA-matched allogeneic
Epstein-Barr virus-specific CTLs (obtained from a frozen bank of CTLs derived
from healthy blood donors) to 8 patients with PTLD unresponsive to standard
treatments. The infusions were well
tolerated and neither graft-vs.-host disease nor enhanced graft rejection
developed in any of the patients.
Three patients achieved a complete remission after 1-4 infusions and
have remained free of disease for 11, 17, and 28 months, respectively. One additional patient had a partial
remission after 2 infusions. Two patients did not respond after 3-6 infusions
and 2 patients died rapidly with progressive disease. These preliminary results suggest that
partly HLA-matched allogeneic CTLs are a potentially effective therapy
against refractory PTLD and warrant further investigation. (Haque T, et al. Lancet 2002;360:436-442) RITUXIMAB Synergy with glucocorticoids
(GCs). Although GCs are
often given in conjunction with rituximab, the effects of GCs on
rituximab-related antitumor mechanisms of action are unknown. Andrea Rose and coworkers at the Fred
Hutchinson Cancer Research Center (Seattle, WA) observed that the addition of
dexamethasone to rituximab induced G1 arrest in all B-cell non-Hodgkin
lymphoma (NHL) cell lines tested (9 of 9) and resulted in synergistic
inhibition of growth in 6 of 9 cell lines.
Furthermore, combination dexamethasone and rituximab resulted in
supra-additive increases of phosphatidylserine exposure and hypodiploid DNA
content (in 5 and 3 cell lines, respectively). Complement-dependent and
antibody-dependent cell-mediated cytotoxicities (CDC and ADCC) were not
enhanced or impaired with simultaneous dexamethasone and rituximab
administration. However,
pre-incubation with dexamethasone reduced cell lysis in ADCC assays in 4 cell
lines, while dexamethasone pre-exposure increased cell sensitivity to CDC in
3 cell lines. These in vitro
experiments demonstrated that the addition of GCs to rituximab can result in
synergistic antiproliferative and apoptotic effects in B-cell NHL cell lines
and provide a rationale for clinical trials investigating the potential
benefit of combination GC plus rituximab therapy. (Rose AL, et al. Blood
2002;100:1765-1773) Treatment of
fludarabine-associated immune thrombocytopenia (ITP). Upendra Hegde and colleagues from the
National Cancer Institute (US) report the successful use of rituximab therapy
in 3 chronic lymphocytic leukemia (CLL) patients with severe
fludarabine-associated ITP (an uncommon untoward effect of fludarabine
treatment). ITP developed during the
first fludarabine cycle in 1 patient and during the third cycle in 2
patients. The platelet count nadirs
were <10,000/mL in all 3
cases and did not respond to steroids or intravenous immunoglobulin
administration. Rituximab therapy
(375 mg/m2 weekly for 4 weeks) resulted in an increase of the
platelet counts to baseline levels in all 3 cases. Rises in the platelet counts were noted within the first week
of rituximab treatment and the response durations were 17+, 6+, and 6 months,
respectively. These results show that
rituximab treatment can rapidly reverse fludarabine-associated ITP in patients
with CLL. (Hegde UP, et al. Blood 2002;100:2260-2262) IMATINIB MESYLATE Molecular targeting of
platelet-derived growth factor B (PDGFB). Imatinib mesylate (Gleevec; Novartis
Pharmaceuticals) selectively inhibits PDGFB, ABL, and KIT kinases. Brian Rubin and colleagues report the
treatment of a patient with dermatofibrosarcoma protuberans, a tumor caused
by the activation of the PDGFB receptor (a transmembrane tyrosine kinase),
with imatinib mesylate 400 mg bid.
Within 2 weeks of treatment initiation, the hypermetabolic uptake of 18F-labeled
fluorodeoxyglucose (FDG) fell to background levels by positron emission
tomography. After 4 months of
therapy, tumor volume had decreased by >75% allowing for resection of the
mass. No viable tumor was found in
the resected specimen (achievement of complete histologic response). This case report demonstrates that
inhibition of PDGFB receptor tyrosine kinase activity can result in
significant antineoplastic activity in at least one type of solid tumor
(dermatofibrosarcoma protuberans). (Rubin BP, et al. J Clin Oncol 2002; 20:3586-3591) |
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