RESUMO
Background: There is contradicting evidence on vitamin D levels and cancer mortality rates. In this study, we aimed to evaluate the impact of baseline vitamin D level on the outcome in patients with estimated glomerular filtration rate (EGFR)-mutant advanced non-small-cell lung cancer (NSCLC) who received either gefitinib or gefitinib with chemotherapy (pemetrexed and carboplatin) as first-line therapy in a prospective randomized study. Methods: This was a post hoc analysis of a phase III randomized trial comparing gefitinib with gefitinib with carboplatin and pemetrexed in patients with advanced NSCLC with activating EGFR mutations in the first-line setting. As a part of regular practice, baseline vitamin D levels were measured using circulating 25(OH) levels in blood. We included 334 patients who had baseline vitamin D levels in the study and evaluated the effect of the vitamin D level on oncologic outcomes. Results: There were 136 (40.7%) patients with a sufficient (>20 ng/mL) baseline vitamin D level, and 198 (59.3%) patients who were deficient in vitamin D (<20 ng/mL). The median progression-free survival (PFS) in patients with normal vitamin D levels was 17 months, whereas that in patients with deficient vitamin D levels was 15 months, with a hazard ratio of 1.45 (95% confidence interval [CI] = 1.03-2.06). The median overall survival (OS) in patients with normal vitamin D levels was 28.6 months, whereas that in patients with deficient vitamin D levels was 28.5 months, with a hazard ratio of 1.17 (95% CI = 0.81-1.68). On multivariate analysis, only 2 factors impacted the PFS, the baseline vitamin D level, and the treatment regimen; other factors like age, sex, disease stage, and performance status did not. Conclusions: Baseline vitamin D levels have a significant impact on PFS, whereas OS is not affected by the baseline vitamin D levels on patients receiving targeted therapy for EGFR-mutant lung cancer. Trial registration: The trial was prospectively registered with the Clinical Trial Registry of India, registration number CTRI/2016/08/007149. The date of the registration was 5 August 2016.
RESUMO
BACKGROUND: Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF. METHODS: In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events. RESULTS: 495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95% CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P = 0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS was 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P < 0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P < 0.0001). CONCLUSION: NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival.