Small cell lung cancer requires complex therapeutic strategies

Among the most aggressive malignancies is small cell lung cancer. The field of oncology has seen a plethora of new chemotherapeutics and treatment strategies emerge in the past several years, but such developments unfortunately have not extended to the realm of small cell lung cancer. As such, this is a disease that continues to portend a poor prognosis, and most patients present with extensive-stage disease. The following case illustrates just how acute this illness can be.

A 53-year-old man presented via the ED for gradually worsening dyspnea. His past medical history was significant for chronic obstructive pulmonary disease, and he had approximately a 50-pack per year smoking history. Additionally, he had been having progressive difficulty swallowing in the past month, such that he had an almost complete inability to swallow solid foods. Examination was significant for hypoxia with an 89% oxygen saturation on room air, and the lungs had decreased air entry and occasional wheezes on the right side. Neurologic exam elicited horizontal nystagmus but no other abnormalities. In addition, his initial workup included a chest X-ray. This study revealed a large right hilar mass, and a subsequent CT scan measured this mass as 9 cm in greatest dimension. This also showed that the mass had compressed approximately 90% of the lumen of the distal esophagus.

Given the smoking history and the hilar mass, the suspicion was highest for lung cancer. A biopsy was performed by way of an endoscopic ultrasound; the histology was that of SCLC. Further staging evaluation with a PET scan showed a maximum standardized uptake value of 11.7 in the mass, as well as some activity in the neck. MRI scan of the brain demonstrated a solitary 1x1-cm left temporal solitary brain metastasis, with minimal vasogenic edema.

Course of treatment

At this point, the patient was diagnosed with extensive-stage SCLC, with metastasis to the brain. Corticosteroids were begun for the brain lesion, and urgent neurosurgery and radiation oncology consultations were requested. Unfortunately, the lesion was not in a location where it could be resected; therefore, radiation to the brain was planned.

However, given that the patient was markedly symptomatic with hypoxia and because SCLC is classically chemosensitive, it was decided to give the first cycle of cisplatin and etoposide urgently, followed by radiation therapy to the brain. Accordingly, the patient received the chemotherapy as an inpatient. He tolerated it well, and within a few days, he already perceived a difference in his symptoms. As an example, he was able to swallow foods much more easily. His respiratory symptoms were also ameliorated to some extent, and he was discharged. As an outpatient, he received stereotactic radiation therapy to the brain mass.

Amit Mehta

Just before the date of the patient’s next cycle of chemotherapy, he presented to an outside hospital with significant shortness of breath. A pleural effusion was found as the cause, and a therapeutic thoracentesis was performed. At this point, the outside hospital requested a transfer to our medical center. In transit, the patient developed atrial fibrillation and was admitted directly to the medical ICU. Fortunately, the rhythm spontaneously converted back to normal sinus overnight. Further workup in the ICU consisted of a CT angiogram to rule out a pulmonary embolus; this was negative, but Doppler studies found a lower leg deep venous thrombosis.

The next day, even after the therapeutic thoracentesis, the patient was still short of breath, and chest imaging demonstrated striking right lung opacification. The concern was raised that he may potentially need a bronchial stent because of the large mass. A subsequent bronchoscopy showed that significant mucus plugging was present, and this was suctioned aggressively, but there was no obstruction requiring a stent placement. Based on the CT scan and bronchoscopy, the assessment was made that the dyspnea was secondary to a combination of right lung volume loss and mucus plugging, along with the pleural effusion.

A multipronged approach had to be employed for this situation. The mucus plugging was already suctioned, and the patient’s condition improved. For the hilar mass, which had shrunk somewhat after the first cycle of chemotherapy, we proceeded with the second cycle of treatment, again as an inpatient. Thirdly, to prevent a recurrent pleural effusion, pleurodesis was planned.

Our patient tolerated the second cycle of cisplatin and etoposide well. He also had a chest tube placed, and once the drainage reduced to a minimum, pleurodesis was performed. From admission, the patient’s condition had improved substantially, albeit after going through multiple interventions. He was safely discharged and follows up as an outpatient for ongoing chemotherapy.

Case Discussion

SCLC, in general, is a chemosensitive malignancy. Despite this, of the more than 35,000 newly diagnosed cases per year in the United States, most will succumb to recurrent disease. Although the goal of treatment in limited-stage disease is for cure; in extensive-stage disease, the goal remains palliation. This difference in prognosis is also reflected in the median survival data, with a 2-year survival in limited-stage disease of 20% to 40% but less than 5% in extensive-stage disease. However, once patients recur, the median survival is about 4 months.

In our patient’s case, he was found to have extensive-stage disease upon presentation. In addition, he was symptomatic from the large hilar mass, including symptoms of marked dysphagia to solid foods. Prompt systemic chemotherapy led to a substantial improvement in symptoms, and the patient’s quality of life tangibly improved. Fortunately, he was not symptomatic from the brain lesion. However, despite treatment, he had to be readmitted before the second cycle of treatment. This seemed to be due largely to consequences of the lung mass. In a matter of a few weeks, the patient not only had to deal with a devastating diagnosis, but he also suffered from mucus plugging, lung volume loss, a pleural effusion and a deep vein thrombosis.

The above clinical course illustrates the complexity and acuity of the management of patients with SCLC. Although oncologists may generally prescribe a platinum-based doublet, the mere presence of a lung tumor and a brain metastasis opens the door to a spectrum of emergent pulmonary or neurologic consequences. As a result, the more difficult components of management can often involve dealing with the sequelae of the tumor rather than the treatment.

Recent reports have not uncovered a survival benefit in treatment, but one topic worth mentioning is that of prophylactic cranial irradiation. At least 18% of patients have brain metastases at diagnosis, such as our patient. Most other patients develop brain metastases during the course of the disease. With prophylactic cranial irradiation, a mortality advantage has already been known for limited-stage disease, and in The New England Journal of Medicine in 2007, an advantage was found for extensive-stage disease as well. Specifically, this trial of 286 patients demonstrated that those treated with prophylactic cranial irradiation had a statistically significant lower incidence (15% vs. 40%) of symptomatic brain metastases developing, with a 1-year survival difference of 27% vs. 13% (HR=0.68). Again, our patient was not eligible for this therapy by virtue of his brain lesion found at diagnosis.

Hopefully in the coming years, new positive data on therapeutic strategies will emerge. At ASCO meetings in the past few years, a number of chemotherapy combinations were reported for SCLC but none were found superior to a platinum-based doublet. One trial that garnered some initial excitement was a study in extensive-stage disease of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen. The rationale was that bcl-2 has been shown to be a critical factor in modulating chemoresistance in SCLC. Unfortunately, the study did not meet any of the clinical endpoints, including that for survival.

Amit Mehta, MD, is an attending physician at Regional Cancer Care in Durham, N.C., and is a member of the HemOnc Today Editorial Board.

For more information:

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