Chemotherapy for relapsed small cell lung cancer: A systematic review and practice guideline

Purpose: This clinical practice guideline, based on a systematic review, evaluates chemotherapy options for patients with relapsed small cell lung cancer (SCLC). Methods: Relevant randomized trials and meta-analyses were identified through a systematic search of the literature. External feedback was obtained from practitioners in Ontario, and the guideline was approved by the provincial lung cancer disease site group. Results: Six randomized trials met the eligibility criteria and were included for review. One randomized phase III trial of oral topotecan versus no treatment in patients receiving best supportive care found topotecan to have a significant benefit in terms of 6-month survival and quality of life. A randomized phase III trial compared outcomes of carboplatin in patients receiving a combination of etoposide and cisplatin (EP) and found no significant improvement associated with carboplatin, although it was associated with significantly higher grade 3/4 thrombocytopenia. Two randomized trials directly compared chemotherapy regimens (intravenous [IV] topotecan versus cyclophosphamide, doxorubicin, and vincristine (CAV); and bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide (BTOC) versus EP), but these trials found no significant differences in terms of disease response or survival. IV topotecan was associated with significantly higher toxicities (grade 4 thrombocytopenia and grade 3/4 anemia) and greater improvement in patient-reported symptoms compared with CAV. Two randomized trials of topotecan-treated patients comparing route of administration (IV versus oral) found no significant differences in terms of disease response, survival, or quality of life, although oral administration was associated with increased grade 3 or 4 diarrhea in both trials. Conclusion: Evidence on the clinical benefit of second-line therapy in SCLC is limited. Topotecan is the most studied agent in this population; it has a response and survival benefit in comparison with placebo, but it also has greater toxicity in comparison with CAV. To date, significant differences in terms of response and survival are not evident in studied chemotherapy options.