MINOAS: A Single-arm Translational Phase II Trial of FOLFIRI Plus Aflibercept as First-line Therapy in Unresectable, Metastatic Colorectal Cancer.

BACKGROUND: FOLFIRI/aflibercept is approved as a second-line treatment in metastatic colorectal cancer (mCRC) but there are limited data for its use as a first-line treatment. OBJECTIVE: To investigate the activity and safety of first-line FOLFIRI/aflibercept in mCRC, as well as to prospectively evaluate biomarkers of early response to treatment. PATIENTS AND METHODS: MINOAS was a phase II trial that aimed to evaluate the activity and toxicity of first-line FOLFIRI/aflibercept in mCRC. The primary endpoint was objective response rate (ORR). The secondary endpoints were toxicity, progression-free survival (PFS), overall survival (OS), and the evaluation of CEACAM-positive circulating tumor cells (CTC) and diffusion-weighted (DW)-MRI as biomarkers. RESULTS: Thirty-one patients were enrolled and 259 chemotherapy cycles were administered. At the time of the preplanned interim analysis, all patients had discontinued treatment and the ORR was 61.3%, crossing the activity threshold for trial discontinuation. Median PFS was 8.4 months (95% CI 7.8-9.0). Median OS had not been reached. There was one toxic death due to sepsis; grade 3/4 adverse events included neutropenia (n = 5), diarrhea (n = 6), hypertension (n = 4), asthenia (n = 3), proteinuria (n = 1), and bowel perforation (n = 1). Retaining CTC-negative status predicted better OS compared to continuous detection of CTCs (p = 0.015). Early decrease of the apparent diffusion coefficient (ADC) in DW-MRI was associated with an objective response. CONCLUSION: The activity and safety of first-line FOLFIRI/aflibercept merit further evaluation in randomized studies. CLINICALTRIALS. GOV REGISTRATION NUMBER: NCT02624726.

Small cell carcinoma of the stomach: A report of two cases and a review of the literature.

Primary small cell gastric carcinomas (SCGC) are rare tumors with an aggressive nature, characterized by early, widespread metastases and poor overall prognosis. SCGC shares similar clinicopathological and molecular characteristics with small cell lung carcinoma and is usually treated in a similar manner. Here, two cases of SCGC in young Caucasian male patients are presented. One patient had metastatic and the other locoregional disease. Multimodal treatment was applied in each case; the resulting survival time was 20.2 months in the patient with initially locoregional disease whereas the remains alive and disease-free 20 months after initial diagnosis. A review of the literature is also presented.

A phase II study of metronomic oral vinorelbine administered in the second line and beyond in non-small cell lung cancer (NSCLC): a phase II study of the Hellenic Oncology Research Group.

INTRODUCTION: Frequent administration of low doses of cytotoxic drugs (metronomic chemotherapy) has been suggested to suppress tumour growth possibly by inhibiting angiogenesis. We evaluated a metronomic regimen of oral vinorelbine in pre-treated patients with advanced non-small cell lung cancer (NSCLC). METHODS: Forty-six pre-treated NSCLC patients received oral vinorelbine at a fixed dose of 50 mg three times a week. RESULTS: Treatment was administered as second-line in 12 (26·1%) patients and as third- or further-line in 34 (73·9%). Grade 3-4 neutropenia was observed in 23·9% and febrile neutropenia in 10·9%. Grade 3 fatigue was the most common severe non-hematologic toxicity (10·9%). Response rate was 10·9%; 19·6% achieved disease stabilization. Median tumour progression (TTP) was 2·2 months, median overall survival 9·4 months and the 1-year survival rate was 30·1%. CONCLUSION: The administration of metronomic oral vinorelbine is feasible and results in acceptable clinical efficacy associated with manageable toxicity in a population consisting mostly of heavily pre-treated NSCLC patients.