Treatment of neuroendocrine carcinoma of the gastrointestinal tract: cisplatin + irinotecan vs. cisplatin + etoposide

Japanese investigators report the results of a Phase 3 randomized TOPIC-NEC trial that compared two chemotherapy regimens in patients with advanced gastrointestinal high-grade NEC: etoposide + cisplatin (EP) versus irinotecan + cisplatin (IP).

Of the 170 patients, 69% were male, with the most common primary sites being the hepatobiliary ducts (41%) and stomach (32%), 94% with metastatic or recurrent disease, 46% with large cell carcinoma, and 39% with small cell carcinoma
.
Only 2.
9% of patients have grade 3 neuroendocrine tumors
.

The primary endpoint (overall survival) was similar between EP and IP groups (median, 12.
5 versus 10.
9 months; hazard ratio, 1.
04; P = 0.
80); Progression-free survival was also similar (5.
6 versus 5.
1 months; hazard ratio, 1.
06).

These outcomes were similar in subgroup analyses, including small cell carcinoma vs.
large cell carcinoma, but post-hoc analysis showed that overall survival in the EP group exceeded that of the IP group (median, 18.
6 months vs.
7.
9 months)
in the poorly differentiated pancreatic NEC subgroup.

The EP group had a higher incidence of grade 3 or 4 hematologic toxicity, including neutropenia (91.
5% vs.
53.
7%) and febrile neutropenia (26.
8% vs.
12.
2%); The investigators later revised the study protocol to recommend the prophylactic use of granulocyte colony-stimulating factor (G-CSF)
for patients in the EP group.
The incidence of grade 3 or 4 diarrhea was higher in the IP group than in the EP group (47.
6% vs.
23.
2%)
.