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BioOncology Watch Timely Information for Practicing
Physicians |
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FEBRUARY 2004 ACUTE MYELOID
LEUKEMIA (AML) Gemtuzumab
ozogamicin (GO) combined with intensive
chemotherapy. William Kell and
colleagues evaluated the effect of adding GO, an anti-CD33 monoclonal
antibody chemically linked to calicheamicin, to
induction and consolidation therapy in patients <60 years of age as
first-line treatment. Patients (n =
64) received induction chemotherapy with DA (daunorubicin,
ara-C), DAT (DA plus thioguanine),
and FLAG-Ida (fludarabine, ara-C,
G-CSF, idarubicin) with GO administered on Day
1. The GO doses were planned to be
escalated from TRANSPLANTATION BEAM-alemtuzumab reduced intensity allogeneic
stem cell transplantation. Rowena Faulkner et al. report the results of BEAM
(carmustine, etoposide,
cytosine arabinoside, melphalan)-alemtuzumab conditioning therapy in 65 consecutive
patients with lymphoproliferative disease
undergoing transplantation in 6 SOLID TUMORS Three new targeted
therapies. Jeremy Rich and others evaluated the efficacy and
safety of oral gefitinib, a novel epidermal growth
factor receptor (EGFR) tyrosine kinase inhibitor,
in 57 patients with first recurrence of glioblastoma
following surgical resection, radiation, and chemotherapy in most patients. No objective tumor responses were seen
among 11 patients with measurable disease.
The median event-free and overall survival times were 8.1 weeks and
39.4 weeks, respectively. Development
of diarrhea, but not EGFR expression, predicted for favorable survival. A second oral EGFR tyrosine kinase inhibitor, erlotinib,
was evaluated by Denis Soulieres et al. in 115
patients with locally recurrent or metastatic head
and neck squamous cell cancer. A partial response (PR) was achieved in 5
patients (4.3%) and disease stabilization was maintained in 44 patients
(38.3%) for a median duration of 16.1 weeks.
The median overall survival was 6 months and patients who had a least grade 2 skin rashes were observed to have a
survival advantage. No survival
difference was detected based on HER1/EGFR expression. In addition, Udo Vanhoefer and coworkers evaluated a humanized monoclonal
antibody, EMD72000, directed against EGFR in 22 patients with EGFR-positive
advanced solid tumors. EMD72000 was
administered as a 1-hour i.v. infusion once weekly
and the maximum-tolerated dose was 1,600 mg/week. Pharmacodynamic
studies revealed an abrogation of EGFR-mediated cell signaling and objective
responses were achieved in 23% of patients.
Patients received EMD72000 for up to 18 months without cumulative
toxicity. These 3 novel targeted
therapies warrant further investigation.
(Rich JN, et al. J Clin Oncol 2004;22:133-142;
Soulieres D, et al. J Clin Oncol
2004;22:77-85; Vanhoefer U, et al. J Clin Oncol 2004;22:175-184) GASTROINTESTINAL
STOMAL TUMORS (GISTS) Kinase
mutations predict response to imatinib. GISTs are mesenchymal neoplasms
of the gut wall that constitutively express activated mutant forms of KIT
(CD117) or tyrosine kinase platelet-derived growth
factor receptor alpha (PDGFRA).
Michael Heinrich and coworkers analyzed pretreatment pathology
specimens for mutations of KIT or PDGFRA from patients with metastatic GIST enrolled onto a phase II study of imatinib (Gleevec; Novartis Pharmaceuticals). Activating mutations of KIT and PDGFRA were
found in 112 (88.2%) and 6 (4.7%) patients, respectively. The partial response (PR) rate to imatinib was 83.5% for patients with GISTs
that had an exon 11 KIT mutation (n = 85) compared
to PR rates of 47.8% for GISTs with an exon 9 KIT mutation (n = 23) (p = 0.0006) and 0% for GISTs with no detectable KIT or PDGFRA mutation (p
<0.0001). These data show that the
mutational status of KIT and PDGFRA is predictive of clinical response to imatinib. (Heinrich MC, et al. J Clin Oncol
2003;21:4342-4349) HYPEREOSINOPHILIC
SYNDROME (HES) Anti-interleukin-5
antibody therapy. Sabine-Gisela Plotz et
al. report treatment results in 3 patients with HES and dermatologic
manifestations with mepolizumab, a neutralizing
anti-interleukin-5 antibody. Eosinophil counts fell to the normal range within 24
hours of starting mepolizumab therapy and serum
levels of eosinophil cationic protein normalized
within 2 days. The dermatitis was
controlled in all 3 patients, leukopenia was not
observed, and no adverse events were reported. These early findings show that further
study of mepolizumab treatment of HES is warranted.
(Plotz S-G, et al. N Eng J Med 2003;349:2334-2339) |
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