Sequential administration of cisplatin-etoposide followed by topotecan in patients with extensive stage small cell lung cancer. A multicenter phase II study.
OBJECTIVE
To evaluate the activity of the sequential administration of cisplatin-etoposide (PE) followed by topotecan (TOP) in patients with extensive stage small cell lung cancer (SCLC).


METHODS
Previously untreated patients with extensive stage SCLC received 4 cycles of cisplatin 75 mg/m(2) IV on day 1 and etoposide 100 mg/m(2) IV on days 1-3 every 21 days followed by 4 cycles of TOP 1.5 mg/m(2) IV on days 1-5 every 21 days.


RESULTS
Thirty-eight patients were entered in the study. Their median age was 63 years and the performance status (WHO) was 0 for 5, 1 for 25 and 2 for 8 patients. All patients were evaluable for toxicity and 32 for response to PE and 25 to TOP. Of the 38 patients receiving PE, 1 (3%) patient achieved complete response (CR) and 17 (45%) partial responses (PR) for an overall response rate to PE of 47% (95% confidence interval: 36.7-68.5%). Four (23.5%) of the 17 patients with PR after PE, achieved CR with TOP. None of the patients with stable or progressive disease after PE responded to TOP. The response rate of the 27 patients receiving TOP following PE was 15% (95% confidence interval: 1.4-28.2%). After a median follow up of 9 months, the median duration of response was 6.5 months, the time to tumor progression 6.5 months, the median survival 8.5 months and the 1-year survival 34%. A total of 136 cycles of PE and 89 cycles of TOP have been administered with a median of 4 cycles/patient for each regimen. There were 2 toxic deaths after PE associated with grade IV febrile neutropenia. Treatment delays due to toxicity occurred in 17 (12%) cycles of PE and 20 (22%) cycles of TOP while doses were reduced in 7 (5%) and 4 (4%) cycles, respectively. Grade 3-4 neutropenia, thrombocytopenia and febrile neutropenia occurred in 24, 2 and 3% of PE cycles and 21, 12 and 1% of TOP. Non-hematologic toxicity was mild. The delivered dose intensity was 100% for PE and 93% for TOP.


CONCLUSIONS
The sequential administration of TOP after PE is associated with manageable toxicity and may increase the number of CRs in patients with chemosensitive extensive stage SCLC. However, based on this data and the lack of survival benefit in a previous phase III study, the sequential regimen should not be used outside of a clinical trial.
Mavroudis
D
D
Department of Medical Oncology, School of Medicine, University of Crete, University General Hospital of Heraklion, PO Box 1352, Heraklion, Crete 71110, Greece. mavrudis@med.uoc.gr
Pavlakou
G
G
Blazoyiannakis
G
G
Veslemes
M
M
Apostolopoulou
F
F
Kouroussis
Ch
Ch
Kakolyris
S
S
Agelaki
S
S
Androulakis
N
N
Vardakis
N
N
Magkanas
E
E
Samonis
G
G
Georgoulias
V
V
D000328:Adult; D000368:Aged; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D005047:Etoposide; D019772:Topotecan; D002945:Cisplatin