When I am asked to evaluate a patient with newly diagnosed extensive-stage small cell lung cancer (SCLC), I do make sure that a baseline imaging of the brain is done, since brain metastasis is so common in patients with SCLC. I order a bone scan only in the presence of symptoms of bony involvement. I do not believe PET scans offer additional useful information in patients with extensive stage SCLC.
A quick note about pathology: Patients with large-cell carcinoma with neuroendocrine features should be treated more like non-small cell lung cancer (NSCLC).
My preferred regimen, not surprisingly, for patients with ECOG PS 0-2 ES-SCLC patients is carboplatin and etoposide. I do not feel that cisplatin, with the additional associated toxicities, offers any additional benefits here (for limited-stage SCLC, a topic of a future piece in this series, my own choice of platinum will be cisplatin when possible).
I re-evaluate after two cycles of chemotherapy and in the absence of progression, I continue up to a minimum of four cycles. For those who continue to show response after the fourth cycle of therapy, I would give perhaps two additional cycles of carboplatin and etoposide.
I have rarely, if ever, gone past six cycles of therapy. Based on what we have seen over the past few years from studies conducted in North America, I do not see any value in replacing etoposide with irinotecan in the front-line setting.
However, irinotecan and platinum combination would be reasonable in those rare patients who develop allergy to etoposide. I may consider using single-agent etoposide in the frail elderly or those with a performance status of 3 or worse.
I try my best to avoid using systemic chemotherapy concurrent with whole brain radiation. I usually wait for a week or so after the whole brain radiation has been completed. I would be watchful for tumor lysis syndrome with the first cycle of therapy when patients have large volume disease. I prefer to admit them to the hospital for the first cycle in those instances.
After their initial therapy, usually four to six cycles of platinum/etoposide therapy, I would revaluate them fully with CT of the chest and abdomen and a brain MRI. For those with a response, I arrange for a consultation with a radiation oncologist to discuss prophylactic cranial irradiation (PCI).
Thoracic Radiation Remains Controversial
Thoracic radiation remains controversial as to its impact on survival outcomes, but in my opinion is certainly a consideration in those patients who have very robust responses outside the thorax and are otherwise fit.
As this disease is not curable, at some point (typically with two to four months) the disease will progress and patients will develop recurrent disease-related symptoms. I am particularly discouraged when patient develop progressive disease during initial therapy or within two to three months of completion of therapy (so-called “resistant disease”).
I discuss the limited benefits with further therapy and encourage our patients to pursue the best supportive care/hospice care options or offer them topotecan orally or intravenously. I use either a three-day regimen of topotecan or weekly topotecan regimen in this setting.
I am little bit more optimistic in offering therapy for those who progress three months after the completion of their initial therapy. Once again my choice is to use topotecan or irinotecan. I have occasionally used taxanes, vinorelbine, gemcitabine, and doxorubicin in treating patients with SCLC.
It is unfortunate that a disease that typically responds so well to begin with becomes so refractory to therapy in such a short time. I do not ever use erlotinib, imatinib, or bevacizumab in the treatment of SCLC.
A Few Glimmers of Hope
While the past three decades of our search for a better systemic agent has drawn a blank, I do see a few glimmers of hope on the horizon—amrubicin and picoplatin, to mention a few. Let us continue to work hard and enroll patients in clinical trials.