Course Authors
Robert G. Lerner, M.D.
In the past three years, Dr. Lerner has served as a consultant for RPR, and has served on the Speakers' Bureau for Pharmacia & Upjohn.
Estimated course time: 1 hour(s).
Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.
Upon completion of this Cyberounds®, you should be able to:
Understand the meaning of the term "non-small cell lung cancer" (NSCLC)
Discuss The Revised International Staging System for Lung Cancer
Discuss the therapeutic options -- surgery, radiation or chemotherapy -- and their effectiveness vis a vis this disease
List the many different chemotherapeutic agents that are effective for this group of tumors
Recognize that although palliation and prolongation of survival can be achieved, even in far advanced or recurrent cases, there is no single standard regimen and participation in trials should be considered.
Case Presentation
A 40-year-old woman, who was a life-long smoker, was in her usual state of health, when she developed a seizure and sought care in a hospital emergency room. A CT scan showed two cerebral lesions. She underwent a craniotomy and the pathologic diagnosis of the resected lesions was consistent with non-small cell carcinoma of the lung. Evaluation by chest x-ray and CT scan of the neck, chest and abdomen revealed a right lung mass. After referral to an oncologist, she was started on radiation treatment to the whole brain, as well as dexamethasone (Decadron®) and phenytoin (Dilantin®). Chemotherapy with paclitaxel (Taxol®) and carboplatin was begun. She tolerated the first cycle very well. After a brief hospitalization for an anaphylactic reaction related to paclitaxel, this treatment was stopped and the chemotherapy regimen was changed to cisplatin and gemcitabine (Gemzar®) to which she responded to four to five cycles of monthly treatment.
She then developed a right subclavian mass. Although the initial impression was of an abscess, after incision and drainage the histologic examination of the tissue was consistent with metastatic disease from her lung. At this time, her chemotherapy regimen was changed to docetaxel (Taxotere®) and topotecan (Hycamtin®). She received two monthly cycles of this combination before she was brought to the hospital and admitted because of weakness and failure to thrive. Repeat CT scan revealed progressive disease on the right side of the lung with additional small lesions throughout the pulmonary parenchyma. This situation is now being discussed with the patient and her family, with the expectation that she will probably be treated with oral VP-16 (Vepesid®) and offered home hospice care.
Discussion
This case illustrates both the good news and bad news about NSCLC. This patient presented with metastatic disease to the brain and, although about to succumb to her disease, has lived for over a year, time spent with her family.
NSCLC is a group of cancers which includes squamous or epidermoid carcinoma, adenocarcinoma and large cell carcinoma. Excellent illustrations of the various types are available on the Web at http://wwwnmob.nci.nih.gov/lungpics/lungpics.html
They are grouped because, unlike small cell carcinoma of the lung, they are all, potentially, surgically curable. Additionally, small cell (also called oat cell) carcinoma of the lung responds well to chemotherapy, while NSCLC is much more resistant. Most of the histologic subtypes respond similarly but the stage of disease is critical for prognosis and selection of therapy.
Lung cancer is staged according to characteristics of the primary tumor, nodal involvement and the presence of distant metastases both by clinical and pathologic examination. In comparing studies, those using pathologic rather than clinical staging should be given greater weight since pathologic staging is the benchmark. Clinical staging by imaging studies is frequently in error.(1) The Revised International Staging System for Lung Cancer was adopted in 1997.(2) It is available on the web site of the National Cancer Institute.
Stage I cancers have no nodal or metastatic involvement and are divided into A and B according to tumor size. Stage II cancers have nodal involvement or an extensive primary and are subdivided into A and B according to tumor size or involvement of ipsilateral peribronchial or ipsilateral hilar nodes. Stage III A cancers have metastasized to ipsilateral mediastinal or subcarinal lymph nodes or have a primary tumor invading the chest wall, diaphragm, mediastinal pleura, parietal pericardium or are within 2 cm of the carina, combined with lesser nodal involvement. Stage III B cancers have metastasized to contralateral mediastinal or contralateral hilar nodes or have a primary invading the mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina; or separate tumor nodules in the same lobe; or tumor with a malignant pleural effusion. Stage IV is the designation for distant metastatic disease.
Surgery(3),(4),(5) or, in a few cases, radiotherapy(6) can cure localized disease. Surgery is ordinarily the best option for stages I and II disease, with radiotherapy with curative intent for those individuals who can not undergo surgery. Radiotherapy can be palliative in most patients and can be used in combination with surgery. Stage III disease often calls for chemotherapy combined with other modalities. However, this patient presented in Stage IV, a situation that calls for chemotherapy with surgery or radiotherapy for palliative relief of local manifestations.
Many different regimens containing cisplatin or carboplatin produce objective responses and prolongation of survival.(7) Current practice guidelines for the treatment of unresectable non-small cell lung cancer(8) suggest a platinum-based regimen for selected patients but no one regimen is standard. There are many single agents that can be used in these regimens and a change in regimen can produce responses after failure of an earlier regimen, as in this patient. Several meta-analyses have shown a survival advantage in patients with inoperable stages III B or IV cancers.(9),(10),(11) Radiotherapy should be used for local palliation, as needed, for such manifestations as brain metastases, bone metastases, superior vena cava syndrome, etc. This case also demonstrates that when a brain metastasis presents as the initial manifestation, significant palliation can still be achieved, either with surgery or radiation.
Recurrent disease in this patient did not occur in the brain, which was irradiated as part of her initial therapy. However, recurrent disease occurs in the brain in almost half the patients treated with resection of the primary tumor and postoperative radiotherapy. If there is no extracranial tumor at the time of recurrence, surgical excision can prolong survival(12) and radiosurgery can be used for unresectable brain metastases.(13) Thus, even in recurrent disease, treatment options include chemotherapy, palliative radiotherapy, stereotactic radiosurgery and surgical resection of isolated cerebral metastasis. Laser therapy and locally implanted radiotherapy have also been added to the available options and have been valuable for treatment of symptomatic endobronchial disease.(14)
Summary
In summary, although many treatment options are available and demonstrably beneficial, treatment fails eventually in almost all cases. Therefore, participation in clinical trials should be considered when available.
Postscript
I have been asked whether I, as an oncologist, would want chemotherapy if I had non-small cell lung cancer. An informal survey of my colleagues indicated that they would all choose to have first-line chemotherapy but only some would go beyond that. A recent survey conducted at the 1997 National Comprehensive Cancer Network annual meeting indicated that 64.5% of oncologists and 67% of oncology nurses said yes, they would want chemotherapy.(15)