| Reference (therapy) |
Study type |
Patients |
RT schedule |
Systemic therapy |
Results |
| Le Chevalier et al. [12] |
phase III,
n=353 |
nonresectable squamous cell and large-cell lung carcinoma; WHO 0-1; stage IIIA or IIIB, |
the radiation dose was 65 Gy in each group |
radiotherapy alone (group A), combined treatment (group B) + CT included vindesine, cyclophosphamide, cisplatin, and lomustine |
2-year survival rate was 14% in group A and 21% in group B
distant metastasis rate was significantly lower in group B
local control was poor in both groups (17% and 15%) |
| Schaake-Koning et al. [14] |
phase III,
n=100 |
inoperable stage I, II, or III; no more than 70 years old; medical contraindications to operation; ECOG 0-2; creatinine clearance min. 70 ml per minute. |
radiation was administered for two weeks in a dose of 3 Gy given 10 times, followed by a rest period of three weeks; radiation was again administered for two weeks in a dose of 2.5 Gy given 10 times, |
radiotherapy alone (group A); radiotherapy combined with cisplatin in a dose of 30 mg/m2, given intravenously on day 1 of each treatment week (group B); radiotherapy with cisplatin in a dose of 6 mg/m2 daily (group C) |
Survival was significantly improved in the group C as compared with the group A;
survival in group C was 54 percent at one year, 26 percent at two years, and 16 percent at three years, as compared with 46 percent, 13 percent, and 2 percent in group A.
Survival in group B was intermediate (44 percent, 19 percent, and 13 percent) and not significantly different from survival in either of the other two groups. percent and 28 percent, respectively. |
| Trovo et al. [15] |
phase III,
n=173 |
inoperable, stage III |
RT 45 Gy/15 fractions/3 weeks |
only RT (arm A) versus RT and daily cisplatin dose 6 mg/m2 (arm B) |
median TTP was 10.6 mo for arm A and 14.2 mo for arm B.
Median survivals: 10.3 mo and 9.97 mo
no significant advantage of the combined treatment over radiation therapy only was found
|
| Aupérin et al. [16] |
meta-analysis
n=1764 |
inoperable stage I, II, III and IV; ECOG 0-3; |
RT 45GY to 69.6GY/15-58fractions/3-6weeks |
nine randomised studies
only RT (arm A) and RT with CT(arm B) (cisplatin daily, cisplatin weekly, carboplatin, cisplatin+etoposide; carboplatin+etoposide); |
the hazard ratio of death in arm B to arm A 0.89
absolute benefit of CT 4% at 2 years and 2.2% at 5 yearg,
2- and 5-year survival rates from 21.4% (arm A) to 25.4% (arm B), and from 6.0% (arm A) to 8.2% (arm B) |
| Rowell et al.[17] |
meta-analysis
n=2393 |
inoperable stage I, II, III; ECOG 0-3; |
RT 45GY to 69.6GY/15-58fractions/3-6weeks |
fourteen randomised studies
only RT (arm A) and RT with CT(arm B) (cisplatin daily, cisplatin weekly, carboplatin, cisplatin+etoposide; NR); |
reduction in risk of death at two years (relative risk (RR 0.93);
improvements in two-year locoregional progression-free survival (RR 0.84) and progression-free survival at any site (RR 0.90)
concurrent vs sequential chemoradiotherapy - significant reduction in the risk of death at two years with concurrent treatment (RR 0.86) |
| Aupérin et al. [24] |
meta-analysis
n=1205 |
inoperable stage I, II, III and IV; ECOG 0-2; |
RT 60 and 66 Gy in two trial each, and 56 and 48.5 Gy in one trial each. In one trial the radiotherapy - different in the two arms—there was a 10 days split in the concomitant arm. In the five trials in the sequential arm, patients randomly assigned to concomitant arm received radiotherapy more frequently than those randomly assigned to the sequential arm, |
eleven randomised studies
sequential -cisplatin combined with one drug in four trials, or with two drugs in two trials. Vinorelbine or gemcitabine were used in two trials.
concomitantradiochemotherapy arm, cisplatin was used in five trials, either on a daily basis as single agent (two trials) or combined with other drugs every 4 weeks (three trials). Carboplatin administered weekly was used in only one trial. |
OS: significant benefit of concomitant radiochemotherapy (HR, 0.84) with an absolute benefit of 5.7% (from 18.1% to 23.8%) at 3 years and 4.5% at 5 years.
PFS: significant benefit of concomitant radiochemotherapy HR was 0.90
Concomitant treatment decreased locoregional progression (HR, 0.77);
Concomitant radiochemotherapy increased acute esophageal toxicity (grade 3-4) from 4% to 18% |
| O'Rourke et al. [25]
RT vs RT and CT |
meta-analysis
n=2728 |
inoperable stage I, II, III; ECOG 0-3; |
RT 56 Gy/28 fractions- 70.2 Gy/39 fractions |
nineteen randomised studies
vindesine/cisplatin/mitomycin C; cisplatin/vinblastine; cisplatin/ vinorelbine; carboplatin/paclitaxel |
Chemoradiotherapy reduced overall risk of death (HR 0.71) and PFS (HR 0.69)
Incidence of acute oesophagitis, neutropenia and anaemia were significantly increased with concurrent chemoradiation. |
| O'Rourke et al. [25]
sequential RT and CT vs concomitant RT and CT |
meta-analysis
n=1024 |
inoperable stage I, II, III; ECOG 0-3; |
RT- 56 Gy/28 fractions- 70.2 Gy/39 fractions |
six randomised trials
vindesine/cisplatin/mitomycin C; cisplatin/vinblastine; cisplatin/ vinorelbine; carboplatin/paclitaxel |
OS: significant benefit of concurrent treatment (HR 0.74) with 10% absolute survival benefit at 2 years.
More treatment-related deaths (4% vs 2%) in the concurrent arm without statistical significance (RR 2.02)
increased esophagitis with concurrent treatment (RR 4.96). |
