Annals of Oncology Advance Access originally published online on February 13, 2008
Annals of Oncology 2008 19(3):405; doi:10.1093/annonc/mdn028
© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
in this issue
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Survival outcomes of taxanes in breast cancer
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Despite the increased number of active agents, single-agent
taxane therapy remains one of the standard treatments for metastatic
breast cancer. Paclitaxel and docetaxel share similar chemical
structures and anti-tumor activities, but differ in non-hematologic
toxicity profiles. Since patients recruited to clinical trials
often have better performance status,
Vu et al. [pp. 461–464]
compared the overall survival in patients treated with single-agent
paclitaxel or docetaxel for metastatic breast cancer in a pragmatic
population-based setting. These authors found that while prognostic
factors were balanced between the docetaxel and paclitaxel groups,
median overall survival was significantly longer for docetaxel
versus paclitaxel [10.9 versus 8.3 months; hazard ratio 0.76;
95% confidence interval (CI), 0.62–0.92;
P = 0.006].
The incremental cost-effectiveness ratio was $2434/per month
of median survival gained.
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KRAS in cetuximab-treated colorectal cancer
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For many tumor types including metastatic colorectal cancer,
it is not clear what proportion of tumors are dependent on epidermal
growth factor receptor (EGFR) signaling for their survival,
nor how additional molecular alterations present in the tumor
may influence primary or secondary resistance to EGFR inhibitors.
Predictive markers of response and survival benefit after cetuximab
are urgently required to allow the rational and effective use
of EGFR inhibitors. A recent study has shown objective response
to cetuximab was excluded in KRAS mutated metastatic colorectal
cancer and showed an increase in overall survival for KRAS wild
type (WT) patients. In this issue,
De Roock et al. [pp. 508–515]
present the results of a retrospective analysis of the ability
of KRAS mutations and to predict objective response, progression-free
survival and overall survival benefit in a large series of metastatic
colorectal cancer patients treated with cetuximab. These authors
conclude that KRAS WT status is associated with survival benefit
in cetuximab-treated metastatic colorectal cancer and that this
benefit is even more pronounced in those patients with early
radiological response.
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Toll-like receptors in gastric lymphomas
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Toll like receptors (TLR) as a part of the innate immune system
have been shown to recognize bacterial ligands and some autoantigens,
which results in the activation of proinflammatory cytokines
and chemokines. Recent data also suggest that TLRs influence
apoptosis and cell proliferation. Consequently, TLRs expressed
on tumor cells are possible candidates for interaction of the
tumor with bacterial products or autoantigens. In this issue,
Adam et al. [pp. 566–569] report the results of a study
that aimed to investigate TLR expression in gastric extranodal
marginal zone B-cell lymphomas of MALT-type (eMZBCL) and compare
these results with the TLR expression in other non-Hodgkin lymphomas
infiltrating the stomach, which grow independently of bacterial
or endogenous ligands. These authors conclude that exclusive
TLR4 expression may enable eMZBCL to interact with
Helicobacter pylori and autoantigens, and they suggest that blockade of TLR4
might be a new approach for therapy of eMZBCL of MALT-type.
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HSP90 in melanoma
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Heat-shock proteins (HSPs) are cytoplasmic molecules that facilitate
protein folding, but also act as chaperones, shuttling proteins
to different intra-cellular locations including transport of
proteins to the proteosome for degradation. Agents that target
the 90-kDa HSP, HSP90, are currently in clinical development.
A phase I clinical trial assessing the first HSP90 inhibitor
to enter the clinic (17-AAG) included 11 metastatic melanoma
patients, two of whom had prolonged stable disease (15 and 41
months), suggesting that this agent has clinical activity in
melanoma. In this issue,
McCarthy et al. [pp. 590–594]
report the results of a study that sought to determine the expression
patterns of HSP90 in a large cohort of melanomas and to determine
the differences in expression between benign and malignant tissue.
These authors found that HSP90 expression was significantly
higher in tumors than nevi, and was associated with disease
progression, suggesting that it might be a valuable drug target
in melanoma, as well as a useful diagnostic marker.
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Quote
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"Science has lost its virgin purity, has become dogmatic instead of seeking for enlightenment, and has gradually fallen into the hands of traders."
The poet Robert Graves diagnoses lost purity in Flawed science, damaged human life.
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- Survival outcome and cost-effectiveness with docetaxel and paclitaxel in patients with metastatic breast cancer: a population-based evaluation
- T. Vu, S. Ellard, C. H. Speers, S. C. M. Taylor, M. L. de Lemos, F. Hu, K. Kuik, and I. A. Olivotto
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Survival outcomes of taxanes...
KRAS in cetuximab-treated...