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Michigan Oncology Journal Fall 1999

The Multidisciplinary Lung Cancer Program

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

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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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Please note: The articles listed in the Cancer Center's News Archive are here for historical purposes. The information and links may no longer be up-to-date.