medwireNews: Researchers suggest that combined therapy with the fluoropyrimidine S-1, carboplatin, and bevacizumab followed by maintenance therapy with S-1 and bevacizumab should be first-line treatment for patients with advanced non-squamous non-small-cell lung cancer (NSCLC).
A regimen of carboplatin (area under the concentration-time curve, 5 mg/mL) and bevacizumab (15 mg/kg) on day 1 plus oral S-1 (80 mg/m2 per day) on days 1 to 14 every 21 days was successfully completed by 35 (72.9%) of the 48 patients for at least four cycles. Twenty-nine (60.4%) patients were transferred to subsequent maintenance therapy with S-1 and bevacizumab.
Of the 48 patients who were eligible for evaluation of the treatment response, 26 (54.2%) obtained a partial response, but none achieved a complete response, report Miyako Satouchi (Hyogo Cancer Center, Akashi, Japan) and colleagues.
In all, 22.9% of patients had stable disease and 22.9% experienced disease progression following treatment. The median progression-free survival was 6.8 months and the median overall survival was 22.8 months.
The researchers, writing in Cancer, say the study findings support a favorable toxicity profile for the treatment regimen: "All toxicities were manageable with symptomatic treatment and dose reduction or interruption."
A treatment delay was experienced by 70.8% of patients in the initial combination phase and by 69.0% during maintenance therapy as a result of adverse events that were mostly related to myelosuppression.
During the initial treatment phase, grade 3 and higher hematologic toxicities included neutropenia (31.3%), thrombocytopenia (16.7%), anemia (10.5%), and leukopenia (8.3%). There was no increase in the relative incidence of hematologic toxicities associated with maintenance therapy with S-1 and bevacizumab, with four patients (13.8%) showing grade 3 neutropenia.
Mild or moderate fatigue and gastrointestinal adverse events were the most frequent nonhematologic toxicities, which the authors note is in line with findings from previous studies with combined S-1 and carboplatin.
Findings from a previous phase III study have showed that combining carboplatin with S-1, an oral fuoropyrimidine agent, is as effective and less toxic than standard paclitaxel-carboplatin treatment in NSCLC. Additionally, in preclinical studies, bevacizumab has also been shown to be effective when combined with the fluoropyrimide 5-fluorouracil.
Given the encouraging findings, the researchers call for further randomized trials comparing S-1, carboplatin, and bevacizumab with the current standard of care in previously untreated patients with advanced NSCLC.
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