Weekly alternating therapy with irinotecan plus cisplatin and etoposide plus cisplatin in the treatment of patients with extensive small cell lung carcinoma.
BACKGROUND
Irinotecan has significant activity in small-cell lung cancer (SCLC). The authors' previous phase 1 study of alternating weekly therapy with irinotecan/cisplatin (IP), etoposide/cisplatin (EP), and granulocyte-colony-stimulating factor (G-CSF) support was well tolerated and active in patients with SCLC. A phase 2 trial was conducted to estimate the efficacy of this regimen in previously untreated patients with extensive SCLC.


METHODS
A total of 33 patients were treated between June 2002 and July 2007. Patients received 12 weeks of therapy with cisplatin (20 mg/m(2)) on Day 1 and irinotecan (100 mg/m(2)) on Day 1 and G-CSF on Days 2 to 5 (Weeks 1, 3, 5, 7, 9, and 11) followed by cisplatin (20 mg/m(2)) on Day 1 and etoposide (60 mg/m(2)) on Days 1 to 3 with G-CSF on Days 4 to 7 (Weeks 2, 4, 6, 8, 10, and 12). The primary endpoint was 1-year survival rate.


RESULTS
Grade 4 neutropenia (toxicities were determined using the National Cancer Institute Common Toxicity Criteria [version 2.0]) was noted in 5 (1.5%) of 343 courses with neutropenic fever in only 5 (1%) of 343 courses. One patient died of neutropenic sepsis. Nonhematologic toxicities grade >or=2 were observed in 15 (4%) of 343 courses and were limited to fatigue, hyponatremia, and diarrhea. The overall objective response rate was 89% in 28 assessable patients (no complete responses and 25 partial responses). The median progression-free and overall survivals were 6.0 months and 10.9 months, respectively. The 1-year survival rate was 33%.


CONCLUSIONS
Weekly therapy with IP alternating with EP and G-CSF support was well tolerated in patients with extensive SCLC, but did not demonstrate improved progression-free or overall survival when compared with historical controls at the study institution.
William
William N
WN
Department of Thoracic Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Uyeki
James
J
Johnson
Faye M
FM
Feng
Lei
L
Peeples
Beverly O
BO
Fossella
Frank V
FV
Karp
Daniel D
DD
Blumenschein
George R
GR
Stewart
David J
DJ
Glisson
Bonnie S
BS
D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin