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Current
Cancer Therapy Reviews
ISSN: 1573-3947
Current Cancer Therapy Reviews
Volume 5, Number 1, February 2009
Contents
New Agents–Manifold Consequences: The Management of
Lung and Colorectal Cancer is Changing Pp.
1-19
Christine Armbruster
[Abstract] [Full
text article]
Positron Emission Tomography (PET) in
the Evaluation of Response to Therapy in Non-Small Cell Lung
Cancer Pp. 20-27
Roberto C. Delgado-Bolton and José Luis
Carreras Delgado
[Abstract] [Full
text article]
Cellular and Molecular Mechanisms of
Lymphangiogenesis and Lymphedema Pp. 28-36
Tomer Avraham, Peter J. Quartararo, Sanjay V. Daluvoy
and Babak J. Mehrara
[Abstract] [Full
text article]
Squamous Cell Carcinoma of the Skin:
Current Strategies for Treatment and Prevention Pp.
37-44
Michael A. Bachelor and David M. Owens
[Abstract] [Full
text article]
Utility of Limited Sampling Strategies
for Anticancer Agents in the Clinical Arena: A Systematic
Review Pp. 45-66
Rumi Pattar and Mary H.H. Ensom
[Abstract] [Full
text article]
Current Status of Primary Cytoreductive
Surgery for the Treatment of Advanced Epithelial Ovarian Cancer
Pp. 67-79
Kaei Nasu, Harunobu Matsumoto, Noriyuki Takai and
Hisashi Narahara
[Abstract] [Full
text article]
Abstracts
[Back to top]
New Agents – Manifold Consequences: The Management of
Lung and Colorectal Cancer is Changing
Christine Armbruster
[Full
text article]
1,444,920 new cases of cancer were projected in 2007
in the U.S., half of these patients are suffering from cancers
of the prostate, the breast, the lung, and the colon/rectum.
Colorectal and lung cancer are the most frequent solid tumors
in both women and men. However, the US cancer statistics offer
some hope. The incidence rates of colorectal and lung cancer
rose till 1985 and 1991, respectively after which they fell.
Global statistics is the one side of the coin but successful
prevention and treatment of solid tumors requires the acceptance
that these are not single diseases.
This review focuses on the following topics: 1) Tumor biology:
inflammation, growth factors (EGF, VEGF, IGF and its receptors),
and epigenetic events. 2) Management strategies in diagnosis:
Is early diagnosis feasible? a) Tumor-specific antigens. b)
Radiological methods. c) Endoscopy. d) Contributions of pathology
to diagnosis and treatment decisions. 3) Appropriate patient
selection for treatment purposes. a) Evaluation of tumor tissue.
b) Tumor staging. 4) Therapy se-quencing: drugs, beams, surgery.
5) Clinical trials a) Phase I trials. b) What are the best
inclusion criteria and endpoints? 6) The pipeline. 7) New
drugs and manifold consequences. 8.) Prevention strategies.
9.) Future directions.
[Back to top]
Positron Emission Tomography (PET) in the Evaluation of Response
to Therapy in Non-Small Cell Lung Cancer
Roberto C. Delgado-Bolton and José Luis
Carreras Delgado
[Full
text article]
In modern clinical oncology there is a growing need to diagnose
the presence of disease as soon as possible, even when symptoms
are not yet present or are minimal, to identify the response
to treatment in patients that have been treated and to detect
improvement or worsening of the disease as early as possible.
Conventional imaging methods that rely on morphologic or structural
data are very precise in the delineation of lesions, but frequently
present a limited diagnostic efficacy in the evaluation of
response to oncologic treatments. These imaging methods define
response to treatment as a reduction of tumor volume, without
considering molecular or functional aspects that appear earlier
than the structural or anatomic changes. Positron emission
tomography (PET) and PET-CT with 18F-fluorodeoxiglucose
(FDG) are very useful in monitoring response to treatment,
following chemotherapy and radiotherapy. Many studies have
demonstrated that FDG PET is an accurate method to correctly
detect response to therapy. Moreover, early therapy response
evaluation with FDG PET can predict response to treatment
and patient outcome. This allows tailoring treatments to the
individual patient depending on the chemosensitivity and radiosensitivity
of the tumor. Therefore, FDG PET is a diagnostic imaging method
that has the potential to improve the probability of cure
or improvement and reduce the adverse effects and cost of
unnecessary or ineffective treatments. In the research and
development of new therapies, the non-invasive imaging methods
used are of great importance, especially PET as it supplies
functional and molecular information. PET can be used to assess
all the processes related with the development of a new drug,
especially assessing evolution and outcome. Here we present
a review of the available evidence regarding therapy response
evaluation with PET and PET-CT in non-small cell lung cancer.
[Back to top]
Cellular and Molecular Mechanisms of Lymphangiogenesis and
Lymphedema
Tomer Avraham, Peter J. Quartararo, Sanjay V. Daluvoy
and Babak J. Mehrara
[Full
text article]
Chronic secondary lymphedema is a potentially devastating
condition affecting 90-150 million people worldwide. In the
US, lymphedema is most commonly encountered in the upper extremity
of women who have undergone axillary lymph node dissection
for staging and treatment of breast cancer, though it may
also occur following lymph node dissection for melanoma as
well as certain gynecology oncologic operations. While a great
deal has been elucidated about the biology of lymphatics,
lymphatic development, and the lymphatic system in the past
20 years, considerably less is known about impaired lymphatic
regeneration and the mechanisms that lead to secondary lymphedema.
This deficit in knowledge presents a barrier to the development
of effective treatments or prophylactic measures for chronic
secondary lymphedema. Recent advances in this arena have showed
that pathogenesis of lymphedema is complex, and that effective
treatments for this often devastating condition will likely
require the use of multiple modalities. In this review, we
will discuss the development, anatomy, and physiology of lymphatics
as means of introducing this system to the reader. Further,
the latest advances in the scientific exploration of lymphedema
and lymphatic regeneration will be presented.
[Back to top]
Squamous Cell Carcinoma of the Skin:
Current Strategies for Treatment and Prevention
Michael A. Bachelor and David M. Owens
[Full
text article]
Non-melanoma skin cancer (NMSC) is the most frequent
malignancy in the United States, with over one million new
cases reported annually. Approximately 80% of NMSC are basal
cell carcinomas (BCC), while the remaining 20% of NMSC are
squamous cell carcinomas (SCC). BCC and SCC commonly arise
in regions of the skin subjected to chronic sun exposure implicating
ultraviolet radiation (UV)-induced cellular damage as the
primary causative agent. While surgical excision is an effective
treatment of NMSC, strategies aimed at NMSC prevention have
not been exploited clinically. The application of sunscreens
has been the primary means of prevention by physically blocking
the absorption of UV radiation. However, sunscreens have had
limited success in decreasing NMSC incidence overall, necessitating
more targeted strategies against UV damage. In this review
we will discuss the relevance of recently identified UV-induced
cellular changes, including induction of reactive oxygen species,
immune modulation, and damage to mitochondrial DNA to serve
as potential targets for the chemoprevention of NMSC. Finally,
we will discuss the potential of genes required for the maintenance
of epithelial stem cells in the skin as therapeutic targets
for cutaneous cancer.
[Back to top]
Utility of Limited Sampling Strategies for Anticancer Agents
in the Clinical Arena: A Systematic Review
Rumi Pattar and Mary H.H. Ensom
[Full
text article]
Purpose: To conduct a systematic review of available
limited sampling strategies (LSSs) for all anticancer (other
than platinum) agents and to assess the clinical utility of
such models.
Design: A literature search was conducted using PubMed
and EMBASE up to November 2008. Relevant articles were then
categorized according to modified level of evidence guidelines
of the U.S. Preventive Services Task Force.
Results: Fifty-one studies have been published suggesting
LSSs for the estimation of pharmacokinetic (PK) parameters
for 16 different anticancer agents. These include [number
of studies (n) =1, unless otherwise denoted]: busulfan [levels
II-1, II-2(n=6), III], cladribine (level II-1), cyclophosphamide
(level II-1), docetaxel (level II-1, III), doxorubicin (level
II-1), epirubicin [levels II-1, III(n=2)], etoposide [levels
I(n=3), II-1(n=2), II-2, III], 5-fluorouracil [levels II-1,
II-2, III(n=2)], irinotecan [levels I(n=2), II-2(n=3), III],
melphalan (level I), methotrexate [level II-1(n=3), II-2],
temozolamide (level I), thiotepa (level III), topotecan [levels
I(n=3), II-1, II-2, III], vinblastine (level II-1) and vinorelbine
[levels I, II-2(n=2)].
Conclusion: The 12 level I studies illustrate that
when properly constructed and validated, LSSs have the ability
to estimate PK parameters in cancer patients. However, the
estimated PK parameters need to be related to clinical response
or toxicity in order to demonstrate full clinical utility.
[Back to top]
Current Status of Primary Cytoreductive Surgery for the Treatment
of Advanced Epithelial Ovarian Cancer
Kaei Nasu, Harunobu Matsumoto, Noriyuki Takai and
Hisashi Narahara
[Full
text article]
Ovarian cancer is the third-most common cancer
of the female reproductive tract, yet it has the highest case
fatality ratio of all gynecologic malignancies. Approximately
60% of women diagnosed with epithelial ovarian cancer will
die of the disease, because the majority of patients are diagnosed
with advanced disease.
Surgery followed by chemotherapy is the standard approach
to the management of advanced epithelial ovarian cancer. The
goal of the surgery is optimal cytoreduction prior to the
initiation of chemotherapy. As significant survival benefit
from optimal cytoreduction has also been shown for patients
with advanced disease. The generally accepted definition of
optimal cytoreduction today is a residual tumor diameter no
greater than 1 cm. However, the surgeon should attempt to
achieve complete cytoreduction to a level of no visible disease
or microscopic disease.
The surgical procedures required to achieve complete cytoreduction
depend on the disease distribution. The most common areas
of tumor involvement are the paracolic gutters, the small
bowel serosal and mesentery surfaces, the diaphragmatic and
pelvic peritoneum, the greater and lesser omentum with extension
to the transverse colon, and the sigmoid colon affected by
direct extension from the ovary. In cases of extensive tumor
involvement, optimal cytoreduction may involve a radical en
bloc resection of all involved pelvic viscera and associated
peritoneum, bowel resection, splenectomy, and diaphragmatic
and liver resection. The benefit of such aggressive surgery
outweighs the risk of morbidity in the vast majority of patients.
This paper is a review of the recent information concerning
the definition of optimal cytoreduction, surgical techniques
for maximum cytoreduction, and the selection criteria for
patients.
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