Sequential versus alternating administration of cisplatin/etoposide and topotecan as first-line treatment in extensive-stage small-cell lung cancer: preliminary results of a Phase III Trial of the Hellenic Oncology Research Group.
BACKGROUND
This trial was designed to compare the efficacy and toxicity of sequential versus alternating administration of cisplatin/etoposide and topotecan in patients with previously untreated extensive-stage small-cell lung cancer (SCLC).


METHODS
Two hundred eighty-four chemotherapy-naive patients were randomized between the sequential therapy arm (n=142; 4 cycles of cisplatin 75 mg/m2 intravenously [I.V.] on day 1 with etoposide 100 mg/m2 per day I.V. on days 1-3 followed by 4 cycles of topotecan 1.5 mg/m2 per day I.V. on days 1-5) and the alternating arm (n=142; same doses of cisplatin/etoposide on cycles 1, 3, 5, and 7 and topotecan on cycles 2, 4, 6, and 8). Treatment cycles for both regimens were administered every 3 weeks.


RESULTS
At this preliminary analysis, no statistically significant difference in the overall response rate, duration of response, time to disease progression, or median survival was observed between the 2 arms. A total of 756 cycles of the sequential therapy and 830 cycles of the alternating therapy were administered, with a median numbers of 6 and 7 cycles per patient, respectively. Topotecan was administered in 85 patients on the sequential arm and 132 patients on the alternating arm. Dose reductions for toxicity were similar in both arms. Grade 3/4 toxicities in the sequential and alternating arms, respectively, included neutropenia (51% and 52%; P=NS), anemia (12% and 11%; P=NS), febrile neutropenia (7% and 9%; P=NS), thrombocytopenia (19% and 20%; P=NS), and asthenia (8% and 2%; P=0.02). There were 4 toxicity-related deaths in the sequential arm versus 3 in the alternating arm.


CONCLUSIONS
Our preliminary conclusion is that the sequential and alternating regimens resulted in comparable activity and tolerability in previously untreated patients with extensive-stage SCLC.
Ignatiadis
Michail
M
Department of Medical Oncology, School of Medicine, University of Crete, Greece.
Mavroudis
Dimitris
D
Veslemes
Marinos
M
Boukovinas
John
J
Syrigos
Kostas
K
Agelidou
Maria
M
Agelidou
Athina
A
Gerogianni
Aleka
A
Pavlakou
Georgia
G
Tselepatiotis
Evaggelos
E
Nikolakopoulos
John
J
Georgoulias
Vassilis
V
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
D005047:Etoposide; D019772:Topotecan; D002945:Cisplatin