Background: Nanosomal docetaxel lipid suspension (NDLS) was developed to overcome toxicity issues associated with conventional docetaxel. Docetaxel, cisplatin, 5-fluorouracil (5-FU; DCF) or modified DCF (mDCF) is one of the recommended first-line regimens for patients with metastatic gastric adenocarcinoma (GAC). However, majority of the patients experienced grade 3/4 toxicities with DCF regimen using conventional docetaxel. The present study evaluated the safety and efficacy of NDLS-based mDCF/DCF regimens in patients with metastatic GAC. Methods: In this multicentric, open-label, clinical trial, patients with previously untreated metastatic GAC were enrolled. Patients received either mDCF [NDLS 40 mg/m² on day 1 (D1), C 40 mg/m² on D2 or D3, 5-FU 400 mg/m² bolus on D1, leucovorin 400 mg/m² on D1, 5-FU 1000 mg/m²/day continuous infusion D1 & 2; q2w] for 9 cycles, or DCF [NDLS 75 mg/m² on D1, C 75 mg/m² on D1, 5-FU 750 mg/m²/day for 5 days given as continuous infusion; q3w] for 6 cycles. Prophylactic GCSF (Granulocyte Colony Stimulating Factor)/Peg-GCSF support was allowed in all patients. The primary endpoint was overall response rate (ORR) at week 18. Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety outcomes. Patients were followed up to 1 year. Results: Fifty-two patients were enrolled, with mean (±SD) age of 52 (±9.6) years & male:female ratio of 32:20. Thirty-eight patients qualified for modified intent-to-treat (mITT) analysis for efficacy evaluation (mDCF: 33; DCF:5). At week 18, ORR was 57.9% & DCR was 81.6% in mITT population. In the per-protocol population (n=26), ORR was 61.5% at 18 weeks (mDCF:63.6%; DCF:50%). Safety set included all 52 patients. Any grade adverse events (AEs) were reported in 90.4% (n=47) of the patients; with 40.4% experiencing grade 3/4 AEs. All-grade AEs reported in ≥10% of the patients included anemia, neutropenia, abdominal pain, diarrhea, nausea, vomiting, fatigue, mucositis, decreased appetite, peripheral neuropathy; with majority of AEs being grade 1/2. Most common grade 3/4 AE was neutropenia; observed in 17.3% (n=9) patients (mDCF: 14%; DCF: 33.3%). Conclusions: NDLS-based regimens demonstrated efficacy & improved safety profile in the treatment of metastatic GAC. Clinical trial information: CTRI/2018/01/011450.

NE: not estimable; NR: not reached.