Mature results of prospective randomized trials suggest that combined-modality therapy produces a modest but significant improvement in survival of 5% at 3 years compared with chemotherapy alone.[1,2,3][Level of evidence: 1iiA]
Clinical trials have consistently achieved median survivals of 18 to 24 months and 40% to 50% 2-year survival rates with less than a 3% treatment-related mortality.[3,4,5,6,7][Level of evidence: 1iiA]
No consistent survival benefit has resulted from the following:[8,9,10,11,12,13,14,15][Level of evidence: 1iiA]
Increased dose intensity.
Increased dose density.
Administration of additional drugs.
Altered modes of administration of various chemotherapeutic agents.
Length of treatment. The optimal duration of chemotherapy for patients with LD SCLC is not clearly defined, but no improvement exists in survival after the duration of drug administration exceeds 3 to 6 months. The preponderance of evidence available from randomized trials indicates that maintenance chemotherapy does not prolong survival for patients with LD SCLC.[8,9,10,11,12,13,14,15][Level of evidence: 1iiA]
Dose and timing. The optimal dose and timing of TRT remain controversial.
Multiple clinical trials and meta-analyses addressing the timing of TRT have been published, with the weight of evidence suggesting a small benefit to early TRT (i.e., TRT administered during the first or second cycle of chemotherapy administration).[3,4,5,6,8,9,15,16,17,18,19][Level of evidence: 1iiA]
The amount of time from start to completion of TRT in LD SCLC may also effect overall survival (OS). In an analysis of four trials, the completion of therapy in less than 30 days was associated with an improved 5-year survival rate (relative risk, 0.62; 95% confidence interval, 0.49-0.80; P = .0003).[Level of evidence: 1iiA]
Both once-daily and twice-daily chest radiation schedules have been used in regimens with etoposide and cisplatin. One randomized study showed a modest survival advantage in favor of twice-daily radiation therapy given for 3 weeks compared with once-daily radiation therapy to 45 Gy given for 5 weeks (26% vs. 16% at 5 years; P = .04).[Level of evidence: 1iiA] Esophagitis was increased with twice-daily treatment. Twice-daily radiation therapy has not been broadly adopted. Once-daily fractions to higher doses of greater than 60 Gy are feasible and commonly used; their clinical benefits are yet to be defined in phase III trials.[Level of evidence: 3iiiA]