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Please note: This article is part of the Cancer Center's News Archive and is here for historical
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Gregory P. Kalemkerian, M.D.,
Clinical Associate Professor
Department of Internal Medicine
Co-Director, Thoracic Oncology Program
Lung cancer is the leading cause of cancer-related mortality
in the United States, with an estimated 171,600 new cases
and 158,900 deaths in 1999. Of these, 19,000 new cases and
17,600 deaths will occur in the Michigan- Ohio-Indiana tri-state
area. Non-small cell lung cancer (NSCLC) is responsible for
75 to 80% of all lung cancer cases, while small cell lung
cancer (SCLC) accounts for the remaining 20 to 25%. A variety
of innovative procedures and technologies have been developed
in the past few years that can greatly facilitate the diagnosis
and staging of lung cancer, allowing a more accurate and timely
assessment of appropriate treatment options. The recent development
of combined-modality therapy has led to significant improvements
in the survival of patients with some forms of lung cancer,
particularly locally advanced NSCLC and limited-stage SCLC.
In addition, the use of modern chemotherapeutic regimens can
have a positive impact on both the survival and quality-of-life
of patients with advanced-stage NSCLC and extensive-stage
SCLC. Many of the recent advances in the diagnosis and therapy
of lung cancer require close collaborations between cancer
specialists with differing areas of expertise, as well as
ready access to state-of-the-art technology.
Multidisciplinary Lung Cancer Clinic
In recognition of the changing nature of cancer care, the
University of Michigan Cancer Center has developed a Multidisciplinary
Lung Cancer Clinic in which patients with known or suspected
lung tumors can be evaluated by a team of specialists in a
timely manner. The major goal of this approach is to offer
patients with lung cancer the best possible comprehensive
care along with state-of-the-art standard and investigational
treatment options. In addition, the clinic serves as an educational
resource for patients and their families, as well as for community
health care providers caring for patients with lung cancer.
Each week, the clinic brings together U-M faculty from a variety
of academic disciplines, including thoracic surgery, medical
and radiation oncology, pulmonary medicine, radiology and
pathology. These specialists thoroughly review each patient's
case, including personal examination of the patient, and all
relevant radiographs and biopsy specimens in order to offer
an individualized assessment of appropriate management options.
The participating faculty offer a broad range of services
and expertise in their respective fields. Our thoracic surgeons,
led by Mark Orringer, M.D., Professor of Thoracic Surgery,
and Mark Iannettoni, M.D., Assistant Professor of Surgery,
specialize in the treatment of patients with early-stage disease
and the performance of invasive diagnostic and staging procedures.
They also provide palliative care to patients with advanced-stage
disease by offering interventions such as thoracoscopic talc
pleurodesis and endobronchial photodynamic therapy. Medical
oncologist Gregory Kalemkerian, M.D., Associate Professor
of Medicine, offers a variety of standard and investigational
systemic therapeutic options for patients with all stages
of NSCLC and SCLC, ranging from adjuvant approaches in patients
with resected early-stage NSCLC to investigational chemotherapeutic
trials for patients with relapsed SCLC or NSCLC. James Hayman,
M.D., and George Henning, M.D., Assistant Professors of Radiation
Oncology, are evaluating novel dosing schemes for patients
with locally advanced disease and routinely take advantage
of the 3-D conformational approach developed at the University
of Michigan to minimize treatment-related complications in
patients receiving definitive thoracic radiotherapy. Our pulmonary
medicine specialists, including Fernando Martinez, M.D., Associate
Professor of Medicine, and Douglas Arenberg, M.D., Assistant
Professor of Medicine, are not only experts in diagnostic
bronchoscopy and the pre-operative evaluation of patients
undergoing lung resections, but also assist in the long-term
care of patients with underlying lung disease. Thoracic radiologists
Leslie Quint, M.D., and Ella Kazerooni, M.D., Associate Professors
of Radiology, offer expertise in recommending and interpreting
appropriate diagnostic and staging studies, including transthoracic
CT-guided biopsies. Expert review of pathologic material is
available through the participation of Andrew Flint, M.D.,
Professor of Pathology. The clinic's skilled nursing staff
of Collette Hodges, M.S.N., Sharon Fox, R.N., and Lori Zaremba,
R.N., represents a unique resource - each with many years
of experience in the care of cancer patients. In addition,
the full resources of the U-M Cancer Center, from nutritional
support to social work services, are available to patients
and their families at any time.
Clinical Research
The majority of patients with both small cell and non-small
cell lung cancer present with advanced-stage disease that
is not curable with current therapeutic approaches. In addition,
most patients with locally advanced NSCLC and limited-stage
SCLC eventually relapse and die of treatment-resistant disease
despite a promising response to initial therapy. In light
of the real, but limited, benefits of standard treatment in
these patients, many investigational approaches have been
developed in an attempt to improve the outcome of patients
with lung cancer. The U-M Thoracic Oncology Program offers
eligible patients the opportunity to participate in a variety
of clinical trials, ranging from randomized national cooperative
group studies to locally administered phase I and II trials
developed by our faculty based on their clinical and/or basic
science research (Table 1). In addition to therapeutic trials,
our patients also are given the opportunity to participate
in studies evaluating the effectiveness of palliative care
approaches, such as intensive family home support, to improve
the quality-of-life of lung cancer patients. Another aspect
of the clinical research effort within the program involves
the identification of epidemiologic trends in lung cancer
and the association of these trends with clinical outcome.
These studies have included evaluations of the impact of age
and race on the clinical course of lung cancer patients in
southeastern Michigan (1).
Basic Science Research
Further advances in the treatment of lung cancer will require
a better understanding of the cellular and molecular derangements
that are involved in the development and progression of the
disease. At the U-M Cancer Center, a number of basic science
laboratories are studying the biology of lung cancer with
the goal of developing more effective diagnostic and therapeutic
modalities. Dr. Kalemkerian's interest in experimental therapeutics
resulted in the identification of several vitamin A analogues
(retinoids) and other natural compounds with potent preclinical
activity against lung cancer cells (2, 3). This work has led
to a variety of clinical investigations, including a recently
completed phase II trial of dolastatin 10, a natural marine
product, in patients with advanced NSCLC and an on-going phase
II trial of fenretinide in patients with relapsed SCLC. David
Beer, Ph.D., Associate Professor of Surgery, in collaboration
with Drs. Orringer and Iannettoni, has collected over 300
lung cancer samples from patients undergoing curative resections
at U-M. Analysis of these samples will define novel genetic
alterations that may identify patients with early-stage disease,
predict patient response to therapy or suggest innovative
therapeutic approaches (4). Drs. Arenberg and Strieter, Professors
of Internal Medicine, have done extensive research on the
role of CXC chemokines, naturally occurring mediators of inflammation,
in the regulation of angiogenesis - new blood vessel formation
that is necessary for tumor growth. They have reported that
some of these chemokines can not only block blood vessel formation
but can also inhibit lung cancer growth in mice (5). We are
currently developing a strategy that will allow us to move
this promising finding from the laboratory into the clinics
at the University of Michigan Cancer Center in the near future.
Conclusion
Through the collaborative efforts of a team of outstanding
clinicians and basic scientists, the University of Michigan
Cancer Center's Multidisciplinary Lung Cancer Program is offering
state-of-the-art comprehensive care to patients with known
or suspected lung cancer and is developing novel diagnostic
and therapeutic approaches that will hopefully benefit patients
diagnosed with lung cancer in the future.
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References
- Ramalingam S, Pawlish K, Gadgeel S, Demers R, Kalemkerian GP. Lung cancer in young patients: analysis of a SEER database. J Clin Oncol. 16:651-657, 1998.
- Kalemkerian GP, Slusher R, Ramalingam S, Gadgeel S, Mabry M. Fenretinide inhibits growth and induces apoptosis in small cell lung cancer cell lines. J Natl Cancer Inst. 87:1674-1680, 1995.
- Kalemkerian GP, Ou X, Adil MR, Rosati R, Khoulani MM, Madan SK, Pettit GR. Activity of dolastatin 10 against small cell lung cancer in vitro and in vivo: induction of apoptosis and bcl-2 modification. Cancer Chemother Pharmacol. 43:507-515, 1999.
- Nambu Y, Hughes SJ, Rehemtulla A, Hamstra D, Orringer MB, Beer DG. Lack of cell surface Fas/APO-1 expression in pulmonary adenocarcinoma. J Clin Invest. 101:1102-1110, 1998.
- Moore BB, Arenberg DA, Strieter RM. The role of CXC chemokines in the regulation of angiogenesis in association with lung cancer. Trends Cardiovasc Med. 8:51-58, 1998.
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