NOVEL-1st: an observational study to assess the safety and efficacy of nilotinib in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase in Taiwan.

Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). However, the real-world evidence of nilotinib in newly diagnosed untreated Ph+ CML-CP is limited in Taiwan. The NOVEL-1st study was a non-interventional, multi-center study collecting long-term safety and effectiveness data in patients with newly diagnosed and untreated Ph+ CML-CP receiving nilotinib. We enrolled 129 patients from 11 hospitals. Overall, 1,466 adverse events (AEs) were reported; among these, 151 were serious and 524 were nilotinib-related. Common hematological AEs were thrombocytopenia (31.0%), anemia (20.9%), and leukopenia (14.0%); common nilotinib-related AEs were thrombocytopenia (29.5%), anemia (14.7%), and leukopenia (12.4%). Early molecular response, defined as BCR-ABL ≤ 10% at Month 3, was seen in 87.6% of patients. By 36 months, the cumulative rates of complete hematologic response, complete cytogenetic response, major molecular response, molecular response 4.0-log reduction, and molecular response 4.5-log reduction were 98.5, 92.5, 85.8, 65.0, and 45.0%, respectively. Nilotinib is effective and well-tolerated in patients with newly diagnosed Ph+ CML-CP in the real-world setting. Long-term holistic care and a highly tolerable AE profile may contribute to good treatment outcomes in Ph+ CML-CP under first-line treatment with nilotinib.

Metronomic Cordycepin Therapy Prolongs Survival of Oral Cancer-Bearing Mice and Inhibits Epithelial-Mesenchymal Transition.

Cordycepin (3'-deoxyadenosine) is a natural compound abundantly found in Cordyceps sinesis in natural and fermented sources. In this study, we examined the effects of cordycepin in a human oral squamous cell carcinoma (OSCC) xenograft model. Cordycepin was administered in a regular, low-dose and prolonged schedule metronomic therapy. Two doses of cordycepin (25 mg/kg, 50 mg/kg) were administrated five days a week for eight consecutive weeks. The tumor volumes were reduced and survival time was significantly prolonged from 30.3 ± 0.9 days (control group) to 56 days (50 mg/kg group, the day of tumor-bearing mice were sacrificed for welfare consideration). The weights of mice did not change and liver, renal, and hematologic functions were not compromised. Cordycepin inhibited the OSCC cell viability in vitro (IC50 122.4-125.2 µM). Furthermore, morphological characteristics of apoptosis, increased caspase-3 activity and G2/M cell cycle arrest were observed. In wound healing assay, cordycepin restrained the OSCC cell migration. Cordycepin upregulated E-cadherin and downregulated N-cadherin protein expression, implying inhibition of epithelial-mesenchymal transition (EMT). The immunohistochemical staining of xenograft tumor with E-cadherin and vimentin validated in vitro results. In conclusion, metronomic cordycepin therapy showed effective tumor control, prolonged survival and low toxicities. Cytotoxicity against cancer cells with apoptotic features and EMT inhibition were observed.

Comparison of the efficacy and toxicity of two dose levels of cisplatin/5-fluorouracil as the chemoradiotherapy regimen for the treatment of locally advanced squamous cell carcinoma of the head and neck.

CONCLUSION: The low-dose regimen brought less grade 3?4 neutropenia and mucositis with similar treatment efficacy. It should be further investigated in prospective randomized clinical trials to confirm its effectiveness and tolerability. OBJECTIVES: This nonrandomized study compared the efficacy and toxicity profiles of two dose levels of cisplatin/5-fluorouracil (5-FU) as the chemoradiotherapy regimen for the treatment of locally advanced squamous cell carcinoma of the head and neck. METHODS: Concurrent chemotherapy consisted of two dose levels: a low dose (cisplatin 12 mg/m(2) + 5-FU 600 mg/m(2) per day) or a high dose (cisplatin 15 mg/m(2) + 5-FU 750 mg/m(2) per day). Both were administered as a 5-day continuous infusion in week 1 and week 5 during radiotherapy. RESULTS: With a median follow-up of 44 months, the overall survival and disease-free survival were 35 months and 22 months (n = 67) for the low-dose group and 36 months and 33 months for the high-dose group (n = 96). The 2-year locoregional control rate was 67.2% for the low-dose and 66.8% for the high-dose group. No statistically significant differences were demonstrated in the treatment efficacy end points. The high-dose regimen resulted in significantly more grade 3?4 neutropenia (31.5% vs 10.9%, p = 0.003) and a trend towards more mucositis (62.1% vs 49.3%, p = 0.066).