Recurrent SCLC Treatment
Standard Treatment Options for Patients With Recurrent SCLC
Standard treatment options for patients with recurrent small-cell lung cancer (SCLC) include the following:
At the time of recurrence, many SCLC patients are potential candidates for further therapy.
Although second-line chemotherapy has been shown to produce tumor regression, responses are usually short lived; the median survival is rarely more than 12 months and usually less than 6 months after second-line therapy. Response to first-line chemotherapy predicts for subsequent response to second-line therapy.
As in other chemosensitive tumors (e.g., Hodgkin lymphoma and ovarian epithelial cancer), two main categories of patients receiving second-line chemotherapy have been described: sensitive and resistant. Sensitive patients have a first-line response that lasted more than 90 days after treatment was completed. These patients have the greatest benefit from second-line chemotherapy. Patients with sensitive disease respond to the same initial regimen in approximately 50% of cases; however, cumulative toxic effects may ensue. Resistant patients either did not respond to first-line chemotherapy or responded initially but relapsed within 90 days of completion of their primary therapy. Results from phase II studies of drugs such as topotecan, irinotecan, and gemcitabine indicate that response rates to agents vary depending on whether patients have sensitive, resistant, or refractory disease.[4-8][Level of evidence: 3iiiDii]
Topotecan is standard chemotherapy for recurrent SCLC. Patients with sensitive disease may achieve response to a number of agents including topotecan, irinotecan, taxanes, vinorelbine, paclitaxel, or gemcitabine.[4-11][Level of evidence: 3iiiDii] Response rates to combination agents are generally higher than those reported for single agents;[12,13] however, many studies do not report the patients with sensitive, resistant, or refractory disease.
- A randomized comparison of second-line treatment with either cyclophosphamide, doxorubicin, and vincristine (CAV) or topotecan in patients with sensitive disease reported no significant difference in response rates or survival, but palliation of common lung cancer symptoms was better with topotecan.[Level of evidence: 1iiC]
- A phase III trial comparing chemotherapy with best supportive care (BSC) in relapsed SCLC patients demonstrated that the addition of oral topotecan to BSC significantly increased overall survival and resulted in better symptom control compared with BSC alone.[Level of evidence: 1iiA] The study enrolled 141 patients with chemosensitive or chemoresistant relapsed SCLC who were unsuitable for further standard intravenous chemotherapy. The median survival times for patients receiving topotecan plus BSC were 25.9 weeks versus 13.9 weeks for BSC alone (P = .01).
- A randomized, phase III trial (CWRU-SKF-1598) of 304 patients assessed the use of oral topotecan (2.3 mg/m2/day for 5 days every 21 days) or intravenous topotecan (1.5 mg/m2/day for 5 days every 21 days). Confirmed response rates were 18.3% and 21.9%, respectively.[Level of evidence: 1iiDii] Secondary endpoints of median survival and 1-year survival rates were also similar (33 weeks vs. 35 weeks and 33% vs. 29%, respectively). Patients receiving oral topotecan experienced less grade 4 neutropenia (47% vs. 64.2%) but more diarrhea of all grades (35.9% vs. 19.9%) than with intravenous topotecan. Quality-of-life (QOL) analysis (using a nonvalidated QOL questionnaire) demonstrated no significant difference between the two arms.
Patients with central nervous system (CNS) recurrences can often obtain palliation of symptoms with additional chemotherapy and/or radiation therapy. A retrospective review showed that 43% of patients treated with additional chemotherapy at the time of CNS relapse responded to second-line chemotherapy. The majority of patients treated with radiation therapy obtain objective responses and improvement following radiation therapy.
Some patients with intrinsic endobronchial obstructing lesions or extrinsic compression caused by the tumor have achieved successful palliation with endobronchial laser therapy (for endobronchial lesions only) and/or brachytherapy. Expandable metal stents can be safely inserted under local anesthesia via the bronchoscope, which results in improved symptoms and pulmonary function in patients with malignant airways obstruction.
Patients with progressive intrathoracic tumor after failing initial chemotherapy can achieve significant tumor responses, palliation of symptoms, and short-term local control with external-beam radiation therapy. Only the rare patient, however, will experience long-term survival following salvage radiation therapy.
Treatment Options Under Clinical Evaluation
Treatment options under clinical evaluation for patients with recurrent SCLC include phase I and II clinical trials of new drugs.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent small cell lung cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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- Eckardt JR, von Pawel J, Pujol JL, et al.: Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol 25 (15): 2086-92, 2007. [PUBMED Abstract]
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- Furuse K, Kubota K, Kawahara M, et al.: Phase II study of vinorelbine in heavily previously treated small cell lung cancer. Japan Lung Cancer Vinorelbine Study Group. Oncology 53 (2): 169-72, 1996 Mar-Apr. [PUBMED Abstract]
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