Early results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with 2 and 4 courses of cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) as neoadjuvant chemotherapy for locally advanced gastric cancer

Background

Neoadjuvant chemotherapy is promising to improve the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both active for metastatic gastric cancer.

Methods

Patients with M0 and either T4 or T3 in case of junctional cancer or schirrhous type received 2 or 4 courses of cisplatin (60 mg/m2 at day 8) / S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1) / cisplatin (60 mg/m2 at day 1) / S-1 (80 mg/m2 for 14 days with 2 weeks rest) as neoadjuvant chemotherapy. Then, patients underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was 3-year overall survival. The planned sample size was 120 to achieve 10% improvement of 3-year OS by four courses or by CS with >85% probability of the correct selection.

Results

Between Oct 2011 and Sep 2014, 132 patients were assigned to CS (n = 66; 33 in 2-courses and 33 in 4-courses) and DCS (n = 66; 33 in 2-courses and 33 in 4-courses). Major grade 3/4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet decreased (3.1%/1.5%). Febrile neutropenia was observed in 6.3% of CS and 4.6% of DCS. Major non-hematological toxicities (CS/DCS) were appetite loss (64.1%/76.9%), fatigue (42.2%/47.7%), nausea (31.3%/49.2%), diarrhea (28.1%/40.0%), mucositis (14.1%/32.3%), and vomiting (12.5%/18.5%). Pathological response, defined by disappearance more than one third of the primary tumor, was 42.4% in CS and 51.5% in DCS, while that was 50.0% in 2-courses and 43.9% in 4-courses. Pathological complete response was 10.6% in CS and 6.1% in DCS, while that was 9.1% in 2-courses and 7.6% in 4-courses. R0 resection rate was 72.7% in CS and 81.8% in DCS, while that was 80.3% in 2-courses and 74.2% in 4-courses. No treatment related death was observed.

Conclusions

2- and 4-courses of CS and DCS had acceptable toxicities and led high pathological response as neoadjuvant chemotherapy for gastric cancer. Primary endpoint will be opened in 2018.

Clinical trial identification

UMIN000006378

Legal entity responsible for the study

N/A

Funding

non-profit organization KSATTS

Disclosure

All authors have declared no conflicts of interest.