A randomized clinical trial comparing concurrent and alternating thoracic irradiation for patients with limited small cell lung carcinoma. "Petites Cellules" Group.
BACKGROUND
Although thoracic radiotherapy is considered to be useful for the treatment of patients with small cell lung carcinoma (SCLC), its optimal administration schedule is still controversial.


METHODS
In a multicenter clinical trial, 164 patients with limited SCLC (of whom 156 were eligible for the study) were randomized to receive either concurrent thoracic irradiation, initiated immediately after the second cycle of chemotherapy (Days 30-64) at a dose of 50 grays in 20 fractions, or alternating thoracic irradiation, scheduled in 3 courses between the second, third, fourth, and fifth cycles of chemotherapy with a 7-day rest period after and before chemotherapy at a dose of 20 grays in 8 fractions (Days 36-47 and Days 64-75) and then 15 grays in 6 fractions (Days 92-101). The same chemotherapy regimen (cyclophosphamide-doxorubicin or vindesine-etoposide) was administered every 4 weeks in both groups.


RESULTS
Concurrent radiotherapy-induced lung toxicity led to early termination of this trial when a significant difference was observed (6 cases vs. 1, P = 0.05, 2-sided log rank test). Objective response rates were 89% in the 82 patients of the concurrent radiotherapy group and 95% in the 74 patients of the alternating radiotherapy group. Median survival periods were 13.5 and 14.0 months, respectively, with no significant difference between the two survival distributions (P = 0.15, 2-sided log rank test). Toxic deaths due to bone marrow hypoplasia were similar in both groups (3 vs. 2), but mortality due to lung toxicity (pulmonary fibrosis) was more frequent with concurrent radiotherapy (6 patients) than with alternating radiotherapy (1 patient) in long term analysis (P = 0.05, 2-sided log rank test).


CONCLUSIONS
Although no statistically significant overall survival difference was observed between the two radiation therapy schedules, the better tolerance of the alternating schedule justifies the choice of this schedule with this chemotherapy regimen, although it may not be applicable to other chemotherapy regimens.
Lebeau
B
B
Service de Pneumologie, Hôpital St. Antoine, AP-HP, Faculté de Médecine, St. Antoine Université Paris VI, Paris, France.
Urban
T
T
Bréchot
J M
JM
Paillotin
D
D
Vincent
J
J
Leclerc
P
P
Meekel
P
P
L'Her
P
P
Lebas
F X
FX
Chastang
C
C
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000009:adverse effects; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D011658:Pulmonary Fibrosis / Q000209:etiology; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014751:Vindesine / Q000009:adverse effects / Q000627:therapeutic use
D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D014751:Vindesine