Background: Over the years several pterygium surgical techniques have been developed with the aim of having the least possible recurrence rate. This has been from bare sclera excision which had an ...unacceptable recurrence rate to the current use of conjunctiva autograft with or without various adjuncts. This study was to review the current practice in a typical multi-specialist ophthalmic department. Method: The ophthalmic theatre operating register was retrospectively reviewed to obtain information on all patients who had pterygium excision at the University College Hospital, Ibadan, over a 4-year period from January 1, 2014, to December 31, 2017. Results: A total of 324 pterygium surgeries were performed and final analysis was on 249 (76.9%) surgeries which met the inclusion criteria, male to female ratio of 0.96:1. The commonest surgical technique was excision + 5-Flourouracil (5FU) + conjunctival autograft accounting for 187(75.1%) eyes. In total, postoperative recurrence was recorded in 40 (16.1%) eyes. The subgroup of excision + 5FU + autograft had the least recurrence rate of 18 (9.6%) eyes. Conclusion: A significant majority of the excision was with conjunctiva autograft with an acceptable low recurrence rate compared with most studies.
Colorectal cancer (CRC) represents a major health burden, and is the 3rd leading cause of cancer deaths in the U.S. In the past decade, the median survival among patients with metastatic CRC (mCRC) ...has increased, primarily due to the introduction of irinotecan, oxaliplatin and signal transduction modulators targeting the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways. Studies in first, second and third-line CRC patient populations have demonstrated that approximately 40-50% of all patients with CRC have mutations in the KRAS gene that predicts for non-responsiveness to EGFR-targeted agents. Unfortunately the lack of identification and utilization of this resistance marker in previous clinical trials led to the erroneous treatment of thousands of CRC patients with EGFR-targeted agents at the cost of considerable toxicity and no benefit. Although initially this resistance factor for EGFR-targeted therapy was thought to be relatively straightforward, subsequent studies using more robust analyses have revealed potentially important insights that may further refine the patient population selected for this class of agents. Furthermore, for those patients with KRAS mutations, treatment is restricted to first and second-line combinations of 5-FU/oxaliplatin/irinotecan/bevacizumab. No other options exist for this patient population, and although drug development is ongoing, preliminary results indicate that merely targeting putative resistance pathways may not be sufficient. Thus, there are numerous lessons learned and pathways forward in this disease, all of which rely upon the earlier development and integration of genomic technologies to refine patient selection and identify resistance pathways that may yield rational combination strategies.
We describe results from IMmotion150, a randomized phase 2 study of atezolizumab (anti-PD-L1) alone or combined with bevacizumab (anti-VEGF) versus sunitinib in 305 patients with treatment-naive ...metastatic renal cell carcinoma. Co-primary endpoints were progression-free survival (PFS) in intent-to-treat and PD-L1+ populations. Intent-to-treat PFS hazard ratios for atezolizumab + bevacizumab or atezolizumab monotherapy versus sunitinib were 1.0 (95% confidence interval (CI), 0.69-1.45) and 1.19 (95% CI, 0.82-1.71), respectively; PD-L1+ PFS hazard ratios were 0.64 (95% CI, 0.38-1.08) and 1.03 (95% CI, 0.63-1.67), respectively. Exploratory biomarker analyses indicated that tumor mutation and neoantigen burden were not associated with PFS. Angiogenesis, T-effector/IFN-γ response, and myeloid inflammatory gene expression signatures were strongly and differentially associated with PFS within and across the treatments. These molecular profiles suggest that prediction of outcomes with anti-VEGF and immunotherapy may be possible and offer mechanistic insights into how blocking VEGF may overcome resistance to immune checkpoint blockade.
In patients with unresectable hepatocellular carcinoma, the combination of atezolizumab and bevacizumab was associated with better progression-free and overall survival outcomes, response rate, and ...preservation of quality of life than sorafenib. Serious toxic effects were noted in 38% of patients, similar to that seen in previous studies of these agents.
IMPORTANCE: For patients with RAS wild-type metastatic colorectal cancer, adding anti–epidermal growth factor receptor (anti-EGFR) or anti–vascular endothelial growth factor (anti-VEGF) monoclonal ...antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined. OBJECTIVE: To evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) vs bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label, phase 3 clinical trial at 197 sites in Japan in May 2015–January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic colorectal cancer (final follow-up, January 14, 2022). INTERVENTIONS: Panitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days. MAIN OUTCOMES AND MEASURES: The primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resection rate. RESULTS: In the as-treated population (n = 802; median age, 66 years; 282 35.2% women), 604 (75.3%) had left-sided tumors. Median follow-up was 61 months. Median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio HR for death, 0.82; 95.798% CI, 0.68-0.99; P = .03) and 36.2 vs 31.3 months, respectively, in the overall population (HR, 0.84; 95% CI, 0.72-0.98; P = .03). Median progression-free survival for panitumumab vs bevacizumab was 13.1 vs 11.9 months, respectively, for those with left-sided tumors (HR, 1.00; 95% CI, 0.83-1.20) and 12.2 vs 11.4 months overall (HR, 1.05; 95% CI, 0.90-1.24). Response rates with panitumumab vs bevacizumab were 80.2% vs 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI, 4.4%-17.9%) and 74.9% vs 67.3% overall (difference, 7.7%; 95% CI, 1.5%-13.8%). Median duration of response with panitumumab vs bevacizumab was 13.1 vs 11.2 months for left-sided tumors (HR, 0.86; 95% CI, 0.70-1.10) and 11.9 vs 10.7 months overall (HR, 0.89; 95% CI, 0.74-1.06). Curative resection rates with panitumumab vs bevacizumab were 18.3% vs 11.6% for left-sided tumors; (difference, 6.6%; 95% CI, 1.0%-12.3%) and 16.5% vs 10.9% overall (difference, 5.6%; 95% CI, 1.0%-10.3%). Common treatment-emergent adverse events were acneiform rash (panitumumab: 74.8%; bevacizumab: 3.2%), peripheral sensory neuropathy (panitumumab: 70.8%; bevacizumab: 73.7%), and stomatitis (panitumumab: 61.6%; bevacizumab: 40.5%). CONCLUSIONS AND RELEVANCE: Among patients with RAS wild-type metastatic colorectal cancer, adding panitumumab, compared with bevacizumab, to standard first-line chemotherapy significantly improved overall survival in those with left-sided tumors and in the overall population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02394795
When used as maintenance therapy, the PARP inhibitor olaparib provided a significant progression-free survival benefit in women with ovarian cancer who had a response to primary chemotherapy, ...particularly in those whose tumors were deficient in homologous recombination (e.g.,
BRCA
-mutated tumors). Hematologic toxic effects were observed.
Metastatic colorectal cancer (mCRC) predominantly contributes to cancer-related mortalities secondary to distant metastasis. This study aimed at investigating anti-tumor activity and safety of ...mebendazole in patients with mCRC.
This prospective, randomized double blind placebo-controlled study enrolled 40 mCRC patients who were randomized into two groups; the control group (n = 20) which received 6 cycles of bevacizumab with FOLFOX4 plus placebo tablets BID and mebendazole group (n = 20) which received 6 cycles of bevacizumab with FOLFOX4 plus mebendazole 500 mg orally BID for 12 weeks. Computed tomography scanning and serum levels of carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF), liver and renal parameters were assessed at baseline and after 12 weeks. One-year overall survival and progression free survival (PFS) were also determined. Data were analyzed using paired, independent sample-t-tests, Mann-Whitney U, Chi-Square and Kaplan-Meier tests and p < 0.05 was considered statistically significant.
Mebendazole was well tolerated and its addition to bevacizumab and FOLFOX4 enhanced tumor response to treatment which was translated by significant improvement of overall response rate 12 weeks after intervention 10 % (2) versus 65% (13) for control and mebendazole groups, respectively; p = 0.000 and significant elevation of PFS (median: 3 and 9.25 months for control and mebendazole groups, respectively; p = 0.000). Furthermore, mebendazole produced significant decline in VEGF level (p = 0.006) with non-significant variation in CEA level (p = 0.063).
Mebendazole may represent an attractive candidate for drug repositioning against mCRC secondary to its safety and efficacy in enhancing tumor response to chemotherapy.
NCT03925662, retrospectively.
•Our study aimed at investigating the anti-tumor activity and safety of mebendazole in metastatic colorectal cancer patients.•Mebendazole enhanced tumor response to treatment producing significant improvement of overall response rate after 12 weeks.•Mebendazole produced significant decline of VEGF level 12 weeks after treatment and significant elevation in PFS.•Mebendazole represents an attractive and well- tolerated candidate for drug repurposing against metastatic colorectal cancer.
On Aug 14, 2014, the US Food and Drug Administration approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer on the basis of improved overall survival (OS) after the ...second interim analysis (in 2012) of 271 deaths in the Gynecologic Oncology Group (GOG) 240 trial. In this study, we report the prespecified final analysis of the primary objectives, OS and adverse events.
In this randomised, controlled, open-label, phase 3 trial, we recruited patients with metastatic, persistent, or recurrent cervical carcinoma from 81 centres in the USA, Canada, and Spain. Inclusion criteria included a GOG performance status score of 0 or 1; adequate renal, hepatic, and bone marrow function; adequately anticoagulated thromboembolism; a urine protein to creatinine ratio of less than 1; and measurable disease. Patients who had received chemotherapy for recurrence and those with non-healing wounds or active bleeding conditions were ineligible. We randomly allocated patients 1:1:1:1 (blocking used; block size of four) to intravenous chemotherapy of either cisplatin (50 mg/m2 on day 1 or 2) plus paclitaxel (135 mg/m2 or 175 mg/m2 on day 1) or topotecan (0·75 mg/m2 on days 1–3) plus paclitaxel (175 mg/m2 on day 1) with or without intravenous bevacizumab (15 mg/kg on day 1) in 21 day cycles until disease progression, unacceptable toxic effects, voluntary withdrawal by the patient, or complete response. We stratified randomisation by GOG performance status (0 vs 1), previous radiosensitising platinum-based chemotherapy, and disease status (recurrent or persistent vs metastatic). We gave treatment open label. Primary outcomes were OS (analysed in the intention-to-treat population) and adverse events (analysed in all patients who received treatment and submitted adverse event information), assessed at the second interim and final analysis by the masked Data and Safety Monitoring Board. The cutoff for final analysis was 450 patients with 346 deaths. This trial is registered with ClinicalTrials.gov, number NCT00803062.
Between April 6, 2009, and Jan 3, 2012, we enrolled 452 patients (225 50% in the two chemotherapy-alone groups and 227 50% in the two chemotherapy plus bevacizumab groups). By March 7, 2014, 348 deaths had occurred, meeting the prespecified cutoff for final analysis. The chemotherapy plus bevacizumab groups continued to show significant improvement in OS compared with the chemotherapy-alone groups: 16·8 months in the chemotherapy plus bevacizumab groups versus 13·3 months in the chemotherapy-alone groups (hazard ratio 0·77 95% CI 0·62–0·95; p=0·007). Final OS among patients not receiving previous pelvic radiotherapy was 24·5 months versus 16·8 months (0·64 0·37–1·10; p=0·11). Postprogression OS was not significantly different between the chemotherapy plus bevacizumab groups (8·4 months) and chemotherapy-alone groups (7·1 months; 0·83 0·66–1·05; p=0·06). Fistula (any grade) occurred in 32 (15%) of 220 patients in the chemotherapy plus bevacizumab groups (all previously irradiated) versus three (1%) of 220 in the chemotherapy-alone groups (all previously irradiated). Grade 3 fistula developed in 13 (6%) versus one (<1%). No fistulas resulted in surgical emergencies, sepsis, or death.
The benefit conferred by incorporation of bevacizumab is sustained with extended follow-up as evidenced by the overall survival curves remaining separated. After progression while receiving bevacizumab, we did not observe a negative rebound effect (ie, shorter survival after bevacizumab is stopped than after chemotherapy alone is stopped). These findings represent proof-of-concept of the efficacy and tolerability of antiangiogenesis therapy in advanced cervical cancer.
National Cancer Institute.
PDF
