Carboplatin and paclitaxel plus ASA404 as first-line chemotherapy for extensive-stage small-cell lung cancer: a multicenter single arm phase II trial (SAKK 15/08).
BACKGROUND
Small-cell lung cancer (SCLC) is a highly vascularized tumor. ASA404 is a tumor vascular disrupting agent. This is the first trial to report the effects of combining chemotherapy with ASA404 in SCLC.


METHODS
Patients with untreated metastatic SCLC were treated with carboplatin (area under curve, 6) plus paclitaxel (175 mg/m(2)) plus ASA404 (1800 mg/m(2)) on day 1 every 21 days for up to 6 cycles. The primary endpoint was the progression-free survival (PFS) rate at 24 weeks.


RESULTS
Median age was 61 years; 53% were women, 41% had weight loss; and 96% had a performance status of 0-1. Twelve patients completed all 6 cycles, and most adverse events were related to chemotherapy. Median PFS and time to progression were 7.0 months (95% CI, 5.7-9.4 months) and 7.5 months (95% CI, 5.7-9.4 months), respectively. The progression-free survival (PFS) rate at 24 weeks was 41% (95% CI, 18%-65%). The overall response rate was 94%. The median overall survival time was 14.2 months (95% CI, 8.2-16.0 months) and 1-year survival was 57%. The median follow-up time was 17.7 months. Due to negative results with ASA404 in non-small-cell lung cancer trials, the trial was stopped prematurely after 17 of 56 planned patients were being accrued.


CONCLUSIONS
This is the first report of a clinical trial with a vascular disrupting agent in SCLC. No unexpected toxicity was observed. PFS was not prolonged with carboplatin and paclitaxel plus ASA404.
Department of Oncology and Hematology, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland. martin.frueh@kssg.ch
Martin
M
Früh
Richard
R
Cathomas
Marco
M
Siano
Gregor
G
Tscherry
Alfred
A
Zippelius
Christoph
C
Mamot
Andreas
A
Erdmann
Fatima
F
Krasniqi
Daniel
D
Rauch
Mathew
M
Simcock
Erika
E
Küttel
Pierre
P
Fustier
Miklos
M
Pless
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary*; D016190:Carboplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000556:secondary*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000556:secondary; D016896:Treatment Outcome; D044004:Xanthones / Q000008:administration & dosage
D044004:Xanthones; C066668:vadimezan; D016190:Carboplatin; D017239:Paclitaxel