Updated January 2014
Guideline: Appropriately selected patients with recurrent small cell lung cancer achieve a palliative benefit from second-line chemotherapy.
Level of Evidence: 2
Recurrent SCLC cannot be retreated with curative intent. Patients that have tolerated initial chemotherapy poorly are likely to have worse toxicity with re-treatment. Disease progression within three months is particularly unfavorable. Patients with longer remissions, particularly those that are free from progression for six months to one-year may be considered for combination chemotherapy. When the time to progression is long (a year or more) platinum and etoposide may be repeated. As always, performance status is a powerful prognostic factor and predictor of response plus toxicity.
A number of other drugs have been recommended for recurrent SCLC including topotecan. A randomized trial of patients that were progression-free for at least 2 months compared topotecan to CAV. The results were poor and not significantly different between the arms. Although topotecan has been approved for recurrent SCLC, the five day topotecan regimen is inconvenient and must be monitored carefully for toxicity (Protocol LUSCTOP). Topotecan has never been demonstrated superior to other salvage regimens for improved survival. Other schedules of topotecan such as a weekly regimen may have a better therapeutic index. Oral topotecan has been demonstrated superior to supportive care only in the second-line setting (O’Brien). To date, there is no trial that has shown survival superiority of one salvage regimen over another.
Because of toxicity issues associated with topotecan, irinotecan has been increasingly used by the BCCA lung systemic group. The LUSCPI protocol delivers irinotecan on days 1 and 8 on a 21 day schedule. Irinotecan may be used as a single agent if the time to progression is short. If the time to progression is long and the patient is clinically suitable, irinotecan can be combined with a platinum. This regimen is associated with more predictable myelosuppression and less diarrhea than topotecan (Zatloukal 2010)
Although monotherapy with oral etoposide has been demonstrated inferior to combination chemotherapy as first-line chemotherapy for SCLC, oral etoposide may still be useful in relapsed patients that are reluctant to receive intravenous chemotherapy but would consider oral therapy. Etoposide 50 mg po bid for seven days every three weeks (LUSCPOE) appears less toxic than higher dose regimens. Cyclophosphamide and anthracycline regimens are sometimes used in this setting (Protocol LUSCCAV).
Relapsed SCLC with carcinomatous meningitis has a very poor prognosis that is difficult to change. Improvement in neurological function with intrathecal chemotherapy for carcinomatous meningitis from SCLC is only occasionally observed and such treatment should be considered only for patients with good performance status and reasonably well controlled disease outside the central nervous system. Palliative radiotherapy to areas of symptomatic involvement may be useful in delaying neurological deterioration.
Van Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 17:658-667, 1999.
Murray N, Turrisi A. A review of first-line treatment for small-cell lung cancer. J Thorac Oncol. 1:270-278, 2006
O’Brien M, Ciuleanu T, Tsekov H, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 24:5441-5447, 2006
Zatloukal P, Cardenal F, Szczesna A, et al. A multicentre international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in small cell lung cancer with extensive disease. Ann Oncol 21:1810-1816, 2010