Treatment of Stage IIIB Non-small Cell Lung Cancer with Bevacizumab
I recently discovered that my dad has stage IVA non-small cell lung cancer with a malignant pleural effusion. He is scheduled to undergo chemotherapy using carboplatin and paclitaxel, and his medical oncologist is also considering adding the angiogenesis (VEGF) inhibitor called Bevacizumab. Should he receive Bevacizumab with the chemotherapy?
Charles B. Simone, II, MD, Radiation Oncologist at Penn Medicine, responds:
I am sorry to hear about your father. Although his non-small cell lung cancer has not spread outside of his chest, because of the involvement of the pleural cavity he is not a candidate for curative treatment with either surgery or radiotherapy. Chemotherapy is often recommended for the treatment of Stage IVA non-small cell lung cancer. The two drugs that he will be receiving, carboplatin and taxol, are among the more commonly used drugs in the United States in this situation. In patients who are relatively healthy and have good performance statuses, this combination of drugs is usually well tolerated, although there are significant side effects. These include hair loss, nausea (usually well controlled with antiemetics), lowering of the blood counts with an increased risk of infection, and peripheral neuropathy with numbness of the hands and feet. Bevacizumab is a monoclonal antibody to vascular endothelial growth factor. It likely acts by decreasing new blood vessel growth into tumors, thereby !0starving!1 the tumor. This drug can prolong survival in some patients when delivered with standard cytotoxic chemotherapy. In fact, the Eastern Cooperative Oncology Group demonstrated that among 878 patients with recurrent or advanced (stage IIIB or IV) non-small cell lung cancer, patients randomized assigned to bevacizumab in addition to chemotherapy with paclitaxel and carboplatin had a longer median survival (12.3 months vs. 10.3 months, p=0.003) and higher response rate (35% vs. 15%, p<0.001) [Sandler A, et al. N Engl J Med. 2006;355(24):2542-50].
Bevacizumab is generally well tolerated but also has some side effects that must be considered when adding it to standard cytotoxic chemotherapy. The main side effects of bevacizumab are hypertension and increased risk of bleeding. Bowel perforation. Less commonly, nasal septum and gastrointestinal perforation and renal thrombotic microangiopathy have been reported. Surgery or radiation therapy are not typically administered for patients with a malignant pleural effusion. However, in patients who have had an excellent response to initial chemotherapy and have no evidence of disease outside of the chest on surveillance imaging, these local therapies can be considered in select patients.
If your father's pleural effusion is large, it may cause difficulty with his breathing. If this is the case, removal of some of the fluid may relieve the shortness of breath. In order to prevent reaccumulation of the pleural fluid, a thoracic surgeon can perform a minor procedure, called a pleurodesis.
Overall, it sounds like your dad is being offered a very good treatment regimen for Stage IVA non-small cell lung cancer at the present time. I know that it can be worrisome that there is uncertainty if he will respond to treatment. Unfortunately, not all patients with non-small cell lung cancer will have a response to chemotherapy (defined as a clear cut reduction in the size of the tumor). The only way to determine whether he is going to respond to chemotherapy is to try it. Although chemotherapy for these patient is, unfortunately, not curative, many randomized trials of chemotherapy compared to "best supportive care" in stage IV non-small cell lung cancer have shown that patients who receive chemotherapy survive longer than patients who do not. If your father is clearly not responding, or if he is not tolerating the treatment, then it would not be continued, and he can be considered for other chemotherapy regimens or other therapeutic or palliative options.