Chemotherapy

Although second-line chemotherapy has produced 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.[1] Response to first-line chemotherapy predicts 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.[2] Resistant patients either did not respond to first-line chemotherapy or responded initially but relapsed within 90 days of completion of their primary therapy.[3] 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 C2]

Topotecan is a standard chemotherapy for recurrent SCLC.[9,10] Lurbinectedin, a selective inhibitor of oncogenic transcription, is another option.[11] Patients with sensitive disease may achieve response to a number of agents including topotecan, irinotecan, taxanes, vinorelbine, paclitaxel, or gemcitabine.[4-8,12-14][Level of evidence C2] Response rates for combination agents are generally higher than those reported for single agents,[15,16] and one phase III study reported improved survival for patients with sensitive disease treated with combination cisplatin, etoposide, and irinotecan. However, higher rates of toxicity have been seen.[17]