(Chest. 1999;116:497S-499S.)
© 1999
American College of Chest Physicians
Clinical Presentation of Stage IIIA (N2) Non-small Cell Lung Cancer*
Role of Multimodality Therapy
Joseph S. Friedberg, MD
*
Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, PA.
Correspondence to: Joseph S. Friedberg, MD, University of Pennsylvania Medical Center, 3400 Spruce St, Philadelphia, PA 19104; e-mail: josephf{at}mail.med.upenn.edu
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Abstract
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Neoadjuvant chemotherapy before surgical resection of locally
advanced non-small cell lung cancer (NSCLC) has been shown to improve
survival compared with surgery alone in several randomized clinical
trials. A case report is presented describing the use of paclitaxel and
carboplatin in a multimodality regimen for a patient with stage IIIA N2
NSCLC. Studies are ongoing to determine the optimal type and timing of
chemotherapy.
Key Words: multimodality therapy • neoadjuvant chemotherapy • non-small cell lung cancer • stage IIIA N2 disease • surgery
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Introduction
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Patients
with stage IIIA non-small cell lung cancer (NSCLC) comprise a complex
and heterogeneous group. The expected 5-year survival rate of this
group ranges from < 10 to 40% and is dependent on the extent of
mediastinal nodal involvement.1
2
Currently, the most
successful treatment strategies employ combined modalities, including
surgery.1
Because the majority of patients with stage III
disease die as a result of distant metastases,2
chemotherapy is an integral part of the multimodal approach.
Chemotherapy, administered preoperatively, with or without radiation
therapy, appears to be the most effective neoadjuvant
treatment.1
The following case presentation describes the
diagnostic procedures and the multimodality treatment approach for a
patient who presented with stage IIIA NSCLC.
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Case Report
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A 48-year-old man who had formerly been a heavy smoker presented
with acute-onset shortness of breath. The chest radiograph revealed an
acute pulmonary embolus in the right lung and an incidental solitary
pulmonary nodule in the left upper lobe (Fig 1
). The patient underwent anticoagulation therapy and subsequently had
further pulmonary emboli that required the placement of a vena caval
filter. Filter placement prevented further pulmonary emboli but
complicated the patient’s condition by causing bilateral lower
extremity swelling with documented deep venous thromboses. Pulmonary
function tests revealed an FEV1 of 2.5 L and an
FVC of 3.8 L. Three consecutive sputum cytology tests were negative. A
CT scan of the chest demonstrated a 3.5 x 2.5-cm mass in the left
upper lobe and mediastinal lymphadenopathy (Fig 2
, 3
). A thrombus and a wedge-shaped defect in the right lower lobe that was
consistent with the pulmonary embolus were also found (Fig 4
).
The patient underwent a metastatic workup that consisted of a bone scan
and a head MRI scan, which demonstrated no evidence of distant
metastases. The lower cuts of the chest CT scan revealed no renal,
adrenal, or liver lesions. A bronchoscopy revealed no endobronchial
lesions to the segmental level bilaterally. Cervical mediastinoscopy
revealed metastatic NSCLC in the left paratracheal (4L) station, with
negative nodes at the right paratracheal (4R) and subcarinal (7)
stations. The diagnosis was stage IIIA NSCLC, with positive N2 lymph
nodes.
The patient was treated with neoadjuvant chemotherapy, which consisted
of two cycles of paclitaxel, 175 mg/m2,
and carboplatin, area under the plasma concentration-time curve (AUC) 6
to 7 mg/mL/min, given 3 weeks apart. A repeat metastatic workup
after the second cycle revealed no evidence of metastases. Three weeks
after completing the neoadjuvant chemotherapy course, a left upper
lobectomy with mediastinal lymphadenectomy was performed with a
pericardial fat-pad graft placed on the bronchial stump. The final
pathology report revealed a 3.5-cm, moderately differentiated, T2N2
adenocarcinoma. The patient’s postoperative course included adjuvant
radiation therapy (cumulative dose, 50 Gy) to the mediastinum. Notably,
his leg swelling resolved. He was doing well 1 year after surgery.
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Discussion
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This clinical presentation demonstrates the role of multimodality
therapy in the treatment of locally advanced NSCLC. The use of surgery
with neoadjuvant chemotherapy and adjuvant radiation therapy
contributed to the patient’s 1-year-plus survival time.
The role of neoadjuvant chemotherapy for patients with stage IIIA
NSCLC was established by two randomized phase II trials reported in
1994.3
4
Rosell and colleagues3
compared
preoperative chemotherapy (mitomycin, ifosfamide, and cisplatin)
plus surgery to surgery alone in 60 patients. Patients treated with
neoadjuvant chemotherapy plus surgery had a median overall survival
time of 26 months and a 3-year survival rate of 25% in comparison to 8
months and 3%, respectively, for patients treated with surgery alone
(p < 0.001 for median survival time).3
Roth et
al4
compared surgery alone with perioperative
chemotherapy, which consisted of three preoperative courses of
chemotherapy (cisplatin and etoposide), followed by surgery, and then
an additional three courses of chemotherapy. The 3-year survival rate
was 56% for patients treated with perioperative chemotherapy and 15%
for patients treated with surgery alone. These trials provided support
for the use of neoadjuvant chemotherapy and suggested that decreasing
the tumor burden prior to surgery may prevent the development of
metastases and may minimize the development of drug
resistance.1
2
The development of newer chemotherapeutic agents that are active
against NSCLC has further increased enthusiasm for systemic
treatment.5
Although the previously cited neoadjuvant
trials used older chemotherapeutic agents, extensive phase II trial
experience suggests that the combination of paclitaxel and carboplatin
is effective, well tolerated, and easy to administer.5
6
In one phase II trial, patients with advanced NSCLC who were treated
with paclitaxel and carboplatin demonstrated an objective response rate
of 62% and a 1-year survival rate of 54%.7
Based on
these results, the paclitaxel/carboplatin combination is being
investigated as part of combined modality regimens, including induction
therapy for patients with earlier stage disease.6
Following administration of paclitaxel/carboplatin and a negative
metastatic workup, the presented patient was determined to be eligible
for surgical resection via lobectomy. A lobectomy is the standard
oncologic procedure because it is an anatomic resection incorporating
the removal of the regional lymph nodes.8
Radiation therapy is an integral part of lung cancer
treatment.9
The use of radiation therapy depends on both
tumor-related factors and patient-related factors. Postoperative
radiation therapy is generally reserved for patients who undergo a
complete resection but have lymph node involvement,9
specifically, the presence of stage N2 disease.8
9
Although a positive effect on survival has not been demonstrated,
adjuvant radiation therapy for stage N2 disease decreases the risk of
local recurrence.8
9
Multimodality treatments, including neoadjuvant chemotherapy, are a
feasible option for the treatment of NSCLC. The prognosis for patients
with stage IIIA N2 disease remains poor, but some of these patients are
achieving longer term survival when treated with neoadjuvant
chemotherapy. Ongoing studies are evaluating the optimal type and
timing of chemotherapy and the role of radiation therapy both before
and after surgical resection.10
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Footnotes
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Abbreviation:
NSCLC = non-small cell lung cancer
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References
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Ettinger, DS (1998) Combined-modality treatment for stage IIIa (N2) non-small cell lung cancer: a National Cancer Institute Intergroup study. Cancer Chemother Pharmacol 42(suppl),S71-S74
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Rosell, R, Font, A, Pifarré, A, et al (1996) The role of induction (neoadjuvant) chemotherapy in stage IIIA NSCLC. Chest 109(suppl),102S-106S[Abstract/Free Full Text]
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Rosell, R, Gómez-Codina, J, Camps, C, et al (1994) A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med 330,153-158[Abstract/Free Full Text]
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Roth, JAB, Fossella, F, Komaki, R, et al (1994) A randomized trial comparing perioperative chemotherapy and surgery alone in resectable stage IIIA non-small cell lung cancer. J Natl Cancer Inst 330,153-158
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Bonomi, P (1999) Review of paclitaxel/carboplatin in advanced non-small cell lung cancer. Semin Oncol 26(suppl 2),55-59
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Belani, CP (1998) Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. Oncology 12(suppl 2),74-79[Medline]
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Langer, CJ, Leighton, JC, Comis, RL, et al (1995) Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer: a phase II toxicity, response, and survival analysis. J Clin Oncol 13,1860-1870[Abstract/Free Full Text]
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Kaiser, LR, Friedberg, JS (1997) The role of surgery in the multimodality management of non-small cell lung cancer. Semin Thorac Cardiovasc Surg 9,60-79[Medline]
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Machtay, M, Friedberg, JS (1997) The role of radiation therapy in the management of non-small cell lung cancer. Semin Thorac Cardiovasc Surg 9,80-89[Medline]
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Tonato, M (1996) The role of neoadjuvant chemotherapy in NSCLC. Chest 109(suppl),93S-95S[Abstract/Free Full Text]
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Abstract
Introduction
