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Targeted Therapies Timely
Information for Practicing Hematologists and Oncologists www.tgt-therapies.com |
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DECEMBER 2005 NON-HODGKIN'S LYMPHOMA (NHL) Iodine-131 (I-131) tositumomab in
previously treated patients. Fisher and colleagues analyzed
data from five clinical trials conducted between 1990 and 2001 in which 250
patients with previously treated follicular or transformed low-grade NHL
received a single course of I-131 tositumomab. Overall response
rates ranged from 47% to 68% and complete responses (CRs)
were achieved in 20% to 38% of patients. At a median follow-up of 5.3 years,
the 5-year progression-free survival (PFS) was 17% and median duration of CR
had not been reached. Compared with patients who had a PFS of <12 months,
patients who achieved durable responses had undergone at least four prior
therapies and had refractory disease, elevated lactate dehydrogenase levels,
bulky disease, and a high International Prognostic Index score. In a second
study, Kaminski and others administered a second
course of I-131 tositumomab to 32 patients who had low-grade, follicular, or
transformed low-grade B-cell NHL and had relapsed following an initial
response to I-131 tositumomab. Eighteen patients (56%) achieved a second
response and eight patients (25%) attained a CR. At the time of the report,
five patients had remained in response for 1.8 to 5.7 years. Grade 3 or 4
neutropenia and thrombocytopenia occurred in 50% and 43% of patients,
respectively. Four patients developed myelodysplastic syndromes and one
patient developed acute myelogenous leukemia. Thus, I-131 tositumomab therapy
can result in durable responses in patients with previously treated NHL,
including patients who have relapsed after a single prior course of this
therapy. However, secondary malignancies can occur
following I-131 tositumomab therapy. Retreatment with I-131 tositumomab
should be conducted only in the setting of a clinical trial. (Fisher RI, et al. J Clin Oncol. 2005;23:7565–7573; Kaminski MS, et al. J Clin Oncol. 2005;23:7985–7993.) BREAST CANCER HER2/neu vaccine. Peoples and others are conducting a clinical
trial of a vaccine consisting of E75, an immunogenic peptide associated with
the HER2/neu protein, mixed with
granulocyte/macrophage colony-stimulating factor (GM-CSF) as an
immunoadjuvant. The vaccine was administered to 24 HLA-A2–positive patients
with disease-free, node-positive breast cancer, with 29 HLA-A2–negative
patients being observed prospectively as controls. All vaccinated patients
demonstrated clonal expansion of E75-specific CD8-positive T cells that lysed
HER2/neu–expressing tumor cells. At
a median follow-up of 22 months, disease-free survival in the vaccinated and
control groups was 85.7% and 59.8%, respectively. Median time to recurrence
was 11 and 8 months, respectively. Recurrence was correlated with a weak
delayed-type hypersensitivity response. These data show that the E75 vaccine
is safe and effective in eliciting an immune response. (Peoples GE, et al. J Clin Oncol. 2005;23:7536–7545.) PANCREATIC CANCER Bevacizumab plus gemcitabine. Kindler
and associates report the results of a multicenter, single-arm, phase II
study of the anti–vascular endothelial growth factor (VEGF) monoclonal
antibody bevacizumab plus gemcitabine in previously untreated patients with
metastatic pancreatic cancer. Fifty-two patients were enrolled between 2001 and
2004 and administered gemcitabine 1000 mg/m2 intravenously (IV) on
days 1, 8, and 15 every 28 days. Bevacizumab 10 mg/kg was given after
gemcitabine on days 1 and 15. Eleven patients (21%) achieved partial
remission (PR) and 24 patients (46%) had stable disease. Median PFS and
overall survival times were 5.4 and 8.8 months, respectively. Grade 3 and 4
toxicities included hypertension (19%), thrombosis (13%), visceral
perforation (8%), and bleeding (2%). Plasma VEGF levels at baseline were not
found to correlate with outcome. These data demonstrate that the combination
of bevacizumab and gemcitabine is active in patients with metastatic
pancreatic cancer. A randomized phase III study of gemcitabine plus
bevacizumab versus gemcitabine alone is ongoing in the Cancer and Leukemia
Group B. (Kindler HL, et al. J Clin Oncol. 2005;23:8033–8040.) TRASTUZUMAB Assessment of cardiac dysfunction. Tan-Chiu and associates observed a greater incidence of
congestive heart failure (CHF) in patients who received trastuzumab plus
paclitaxel than in patients who received paclitaxel alone following
doxorubicin and cyclophosphamide chemotherapy (4 of 814 vs 31 of 850
patients). CHF was more common in older patients and patients with a marginal
left ventricular ejection fraction (LVEF) prior to trastuzumab therapy.
Fourteen percent of patients discontinued trastuzumab due to asymptomatic
decreases in LVEF and 4% discontinued due to symptomatic cardiac adverse
events. In a second report, Ewer and colleagues reported increases in LVEF
following trastuzumab withdrawal in 37 of 38 patients who developed
trastuzumab-related cardiotoxicity over a 4-year period. Among these
patients, 25 were retreated with trastuzumab and three experienced recurrent
left ventricular dysfunction. Nine endomyocardial biopsies did not reveal
ultrastructural changes, suggesting that the mechanism of trastuzumab-induced
cardiotoxicity is different from that caused by the anthracyclines. Potential
cardiotoxicity should be carefully considered prior to initiating
trastuzumab; the reintroduction of trastuzumab may be appropriate in some
cases. (Tan-Chiu
E, et al. J Clin Oncol.
2005;23:7811–7819; Ewer
MS, et al. J Clin Oncol.
2005;23:7820–7826.) RENAL
CELL CANCER (RCC) Bevacizumab plus erlotinib. Hainsworth
and others conducted a phase II study in which patients with metastatic RCC
were treated with a combination of bevacizumab (10 mg every 2 weeks IV) and
an epidermal growth factor receptor tyrosine kinase inhibitor (erlotinib; 150
mg/day orally). Among 59 evaluable patients, 15 (25%) had a response and 36
(61%) had stable disease for ≥8 weeks of treatment. At a median follow-up of 15
months, median PFS was 11 months and median survival was not reached. Grade 1
or 2 rash and diarrhea were the most common treatment-related AEs. These data
demonstrate that bevacizumab plus erlotinib is an active therapy for patients
with metastatic RCC. (Hainsworth JD et al. J Clin Oncol.
2005;23:7889–7896.) |
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