Chemotherapy and radiation therapy

Survival. The following results have been reported in clinical trials:

Survival. The following results have been reported in clinical trials:

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.[1-3][Level of evidence A1]

Survival. The following results have been reported in clinical trials:

Clinical trials have consistently achieved median survivals of 18 to 24 months and 2-year survival rates of 40% to 50%, with a treatment-related mortality rate of less than 3%.[3-7][Level of evidence A1]

Survival. The following results have been reported in clinical trials:

No consistent survival benefit has resulted from the following treatment approaches:[8-16]

Survival. The following results have been reported in clinical trials: › No consistent survival benefit has resulted from the following treatment approaches:[8-16]

Increased dose intensity.

Survival. The following results have been reported in clinical trials: › No consistent survival benefit has resulted from the following treatment approaches:[8-16]

Increased dose density.

Survival. The following results have been reported in clinical trials: › No consistent survival benefit has resulted from the following treatment approaches:[8-16]

Administration of additional drugs or other (non–etoposide-containing) platinum-based combination regimens.

Survival. The following results have been reported in clinical trials: › No consistent survival benefit has resulted from the following treatment approaches:[8-16]

Altered modes of administration of various chemotherapeutic agents.

Survival. The following results have been reported in clinical trials: › No consistent survival benefit has resulted from the following treatment approaches:[8-16]

Maintenance chemotherapy.

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.[8-15][Level of evidence A1]

Dose and timing. The optimal dose and timing of TRT remain controversial.

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).[3-6,8,9,15,17-20][Level of evidence A1]

Dose and timing. The optimal dose and timing of TRT remain controversial.

The amount of time from start to completion of TRT in LD SCLC may also affect 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 [CI], 0.49–0.80; P = .0003).[20][Level of evidence A1]

Dose and timing. The optimal dose and timing of TRT remain controversial.

Both once-daily and twice-daily chest radiation schedules have been used in regimens with etoposide and cisplatin.

Dose and timing. The optimal dose and timing of TRT remain controversial. › 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).[17][Level of evidence A1] Esophagitis was increased with twice-daily treatment.

Dose and timing. The optimal dose and timing of TRT remain controversial. › Both once-daily and twice-daily chest radiation schedules have been used in regimens with etoposide and cisplatin.

The phase III CONVERT study (NCT00433563) randomly assigned patients to receive either 45 Gy radiation therapy in 30 twice-daily fractions of 1.5 Gy over 19 days or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups).[21] The primary end point was OS, defined as time from randomization until death from any cause, analyzed by modified intention-to-treat. A 12% higher OS at 2 years in the once-daily group versus the twice-daily group was considered clinically significant to show superiority of the once-daily regimen.

Dose and timing. The optimal dose and timing of TRT remain controversial. › Both once-daily and twice-daily chest radiation schedules have been used in regimens with etoposide and cisplatin. › The phase III CONVERT study (NCT00433563) randomly assigned patients to receive either 45 Gy radiation therapy in 30 twice-daily fractions of 1.5 Gy over 19 days or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups).[21] The primary end point was OS, defined as time from randomization until death from any cause, analyzed by modified intention-to-treat. A 12% higher OS at 2 years in the once-daily group versus the twice-daily group was considered clinically significant to show superiority of the once-daily regimen.

At a median follow-up of 45 months (interquartile range [IQR], 35–58), median OS was 30 months (95% CI, 24–34) in the twice-daily group versus 25 months (95% CI, 21–31) in the once-daily group (hazard ratio for death in the once-daily group, 1.18 [95% CI, 0.95–1.45]; P = .14).

Dose and timing. The optimal dose and timing of TRT remain controversial. › Both once-daily and twice-daily chest radiation schedules have been used in regimens with etoposide and cisplatin. › The phase III CONVERT study (NCT00433563) randomly assigned patients to receive either 45 Gy radiation therapy in 30 twice-daily fractions of 1.5 Gy over 19 days or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups).[21] The primary end point was OS, defined as time from randomization until death from any cause, analyzed by modified intention-to-treat. A 12% higher OS at 2 years in the once-daily group versus the twice-daily group was considered clinically significant to show superiority of the once-daily regimen.

The two-year OS rate was 56% (95% CI, 50%–62%) in the twice-daily group and 51% (45%–57%) in the once-daily group (absolute difference between the treatment groups, 5.3% [95% CI, -3.2% to 13.7%]).

Dose and timing. The optimal dose and timing of TRT remain controversial. › Both once-daily and twice-daily chest radiation schedules have been used in regimens with etoposide and cisplatin. › The phase III CONVERT study (NCT00433563) randomly assigned patients to receive either 45 Gy radiation therapy in 30 twice-daily fractions of 1.5 Gy over 19 days or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups).[21] The primary end point was OS, defined as time from randomization until death from any cause, analyzed by modified intention-to-treat. A 12% higher OS at 2 years in the once-daily group versus the twice-daily group was considered clinically significant to show superiority of the once-daily regimen.

Most toxicities were similar between the groups, except there was significantly more grade 4 neutropenia with twice-daily radiation therapy (129 [49%] vs. 101 [38%]; P = .05). In contrast to the earlier study, there was no difference between the groups in terms of rates of grade 3 to 4 esophagitis or pneumonitis.

Dose and timing. The optimal dose and timing of TRT remain controversial. › Both once-daily and twice-daily chest radiation schedules have been used in regimens with etoposide and cisplatin.

Twice-daily radiation therapy has not been broadly adopted. Once-daily fractions to doses higher than 60 Gy are feasible and commonly used; their clinical benefits are yet to be defined in phase III trials.[21][Level of evidence A1]