Gilberto Lopes

Planning cancer control in Latin America and the Caribbean

Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.

How Uncommon are Isolated Lung Metastases in Colorectal Cancer? A Review from Database of 754 Patients Over 4 Years

BackgroundIt is commonly thought that colon cancer metastases to the lungs without involvement of the liver are rare.MethodsWe performed a retrospective review of all patients with colorectal cancer diagnosed between December 2003 and August 2007 in Singapore. Isolated lung metastases were determined as (1) Definite if there was confirmed histology or cytology of the lung lesion(s) in the absence of liver lesions on CT scan, and (2) Probable if there were only radiological evidence suggestive of lung metastases rather than lung primary also in the absence of liver lesions on CT scan.ResultsThere were 196 patients with rectal and 558 patients with colon cancer (369 left-sided and 189 right-sided). There were 13 definite isolated lung metastases, and the remaining 43 were probable. Twenty-three (12%) patients with rectal cancer and 33 (6%) patients with colon cancer had isolated lung metastases (OR 2.11, 95% CI 1.21–3.70). Patients with ≥pT3 lesions (OR 1.92, 95% CI 0.75–4.93) and ≥pN1 (OR 1.56, 95% CI 0.86– 2.83) were more likely to have isolated lung metastases.ConclusionThe true incidence of isolated lung without liver metastases in colorectal cancer is likely to lie between 1.7% and 7.2%. While the incidence of isolated lung metastases is twice as common in patients with rectal cancer, it is still significant in patients with colon cancer. The absence of liver involvement should not preclude a search for lung metastases.

A phase ii trial of nab-paclitaxel as second-line therapy in patients with advanced pancreatic cancer

Objective:nab-Paclitaxel has been shown to disrupt pancreatic cancer stroma and was effective in combination with gemcitabine in a phase I/II trial. This study was designed to determine the efficacy of nab-paclitaxel monotherapy in previously treated pancreatic cancer patients. Methods:In this phase II trial, patients with advanced pancreatic cancer who progressed on gemcitabine-based therapy, received nab-paclitaxel 100 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle. The primary endpoint was 6-month overall survival (OS). Secondary endpoints were response rate (by Response Evaluation Criteria In Solid Tumors), progression-free survival, safety, and toxicity profile. Results:Among 19 patients treated, the median age was 61 years, 9 (47%) were male patients and 18 (95%) had stage-IV disease. The primary endpoint of the study was reached with a 6-month OS of 58% [95% confidence interval (95% CI), 33%-76%] and an estimated median OS of 7.3 months (95% CI, 2.8-15.8 mo). The median progression-free survival was 1.7 months (95% CI, 1.5-3.5 mo). One patient had a confirmed partial response and 6 (32%) had stable disease as their best response. Nonhematological toxicities were generally mild with grades 1-2 nausea, anorexia, hypocalcemia, and vomiting occurring in 63%, 47%, 37%, and 26% of patients, respectively. Grades 3-4 neutropenia, neutropenic fever, and anemia occurred in 32%, 11%, and 11% of patients, respectively. Only 2 of 15 available tumors stained positive for secreted protein acid rich in cysteine, and neither of these patients benefited from the therapy. Conclusions:nab-Paclitaxel was well tolerated, and it demonstrated preliminary evidence of activity in a subset of patients who progressed on gemcitabine-based therapy.

Large vessel involvement in ANCA-associated vasculitides: report of a case and review of the literature.

Vasculitides are currently classified according to the size of the vessels involved and characteristic clinical and histopathologic findings. Antineutrophil cytoplasmic antibodies (ANCA) and other serologic tests have been used to further characterize small vessel vasculitides. Large vessel involvement in ANCA-associated small vessel vasculitides has been overlooked in the medical literature. Here, we report a case of fatal aortitis and aortic dissection in a patient with microscopic polyangiitis and review reported cases of large vessel involvement in ANCA-associated vasculitides since 1990. We have attempted to characterize this subgroup of patients. Large vessel disease in ANCA-associated vasculitis may present as stenosing large vessel arteritis, aneurysmal disease, aortic dissection, aortic rupture, aortic regurgitation, and death. Prominent perivascular inflammation may present as mediastinal, cervical or abdominal soft tissue masses. ANCA-associated large vessel disease should be considered in the differential diagnosis of these disorders. The epidemiologic, clinical and pathologic characteristics of these patients differ from those of the well-defined large vessel vasculitides such as giant cell (temporal) arteritis or Takayasu’s arteritis. We suggest that large vessel involvement is part of the spectrum of ANCA-associated vasculitis rather than an overlap with other large vessel vasculitides. It occurs in both myeloperoxidase- and proteinase 3-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis, but has not been reported in Churg–Strauss syndrome. Large vessel vasculitis can precede small vessel vasculitis or occur in the absence of small vessel involvement. We hope this report will contribute to the ongoing development of classification systems for the vasculitic syndromes.

Cost-effectiveness of epidermal growth factor receptor mutation testing and first-line treatment with gefitinib for patients with advanced adenocarcinoma of the lung

Epidermal growth factor receptor (EGFR) testing and first‐line therapy with gefitinib for patients with activating mutations is quickly becoming the standard option for the treatment of advanced lung adenocarcinoma. Yet, to date, little is known about the cost‐effectiveness of this approach.

Gefitinib vs. chemotherapy as first-line therapy in advanced non-small cell lung cancer: Meta-analysis of phase III trials

BACKGROUND Gefitinib is an oral tyrosine kinase inhibitor against the epidermal growth factor receptor (EGFR). It has been shown to be active in patients with advanced non-small cell lung cancer (NSCLC) whose tumors contain EGFR mutations. METHODS We performed a meta-analysis of four randomized studies that compared gefitinib with chemotherapy in the first-line treatment of patients with advanced NSCLC: IPASS, North-East Japan, West Japan and first-SIGNAL studies. Patients were selected either on the basis of known EGFR mutations or based on clinicopathologic criteria - non-smokers with adenocarcinomas - associated with increased likelihood of EGFR mutations. RESULTS Nearly 2000 patients were enrolled on these four trials. Median ages ranged from 57 to 64years. Seventy-six percent were women and 86% were non-smokers. Overall, gefitinib was associated with significantly less toxicity than chemotherapy and improved quality-of-life. Gefitinib also produced higher response rates in the EGFR mutation-positive patients (72% vs. 38%, odds ratio 4.04, p<10(-15)), as well as improved progression-free survival (PFS; hazard ratio 0.45, p<10(-16)). Overall survival (OS) was not significantly different between treatment groups (p=0.35). CONCLUSIONS This meta-analysis confirms the results of each individual study and narrows the confidence intervals of these results. In patients with known EGFR mutations or whose tumors are likely to harbor a mutation, upfront gefitinib or chemotherapy are associated with similar OS. Gefitinib is associated with less fatigue, myelosuppression and nausea than chemotherapy (but produces more skin rash, diarrhea and pneumonitis). Patients receiving gefitinib have improved quality-of-life compared to those receiving chemotherapy, making it an appropriate first-line choice.

Meta-Analysis of First-Line Therapies in Advanced Non-Small-Cell Lung Cancer Harboring EGFR-Activating Mutations

Introduction: Tyrosine kinase inhibitors gefitinib, erlotinib, and afatinib have been compared with chemotherapy as first-line therapies for patients with advanced non–small-cell lung cancer harboring epidermal growth factor receptor–activating mutations. This meta-analysis compares gefitinib, erlotinib, afatinib, and chemotherapy. Methods: Literature search was performed using relevant keywords. Direct and indirect meta-estimates were generated using log-linear mixed-effects models, with random effects for study. Study-to-study heterogeneity was summarized using I2 statistics and predictive intervals (PIs). Results: Literature search yielded eight randomized phase 3 clinical trials comparing gefitinib, erlotinib, or afatinib with chemotherapy as first-line therapy in patients with advanced non–small-cell lung cancer during the last 5 years. Hazard ratio meta-estimates for progression-free survival were for gefitinib versus chemotherapy 0.44 (95% confidence interval [CI] 0.31–0.63; 95% PI, 0.22–0.88), erlotinib versus chemotherapy 0.25 (95% CI, 0.15–0.42; 95% PI, 0.11–0.55), afatinib versus chemotherapy 0.44 (95% CI, 0.26–0.75; 95% PI, 0.20–0.98), erlotinib versus gefitinib 0.57 (95% CI, 0.30–1.08; 95% PI, 0.24–1.36), afatinib versus gefitinib 1.01 (95% CI, 0.53–1.92; 95% PI, 0.41–2.42), and erlotinib versus afatinib 0.56 (95% CI, 0.27–1.18; 95% PI, 0.22–1.46). Results for overall response rate and disease control rate were similar. There was no evidence that gefitinib, erlotinib, or afatinib improved overall survival compared with chemotherapy. Conclusion: Gefitinib, erlotinib, and afatinib out-performed chemotherapy in terms of progression-free survival, overall response rate, and disease control rate. Differences among gefitinib, erlotinib, and afatinib were not statistically significant.

Management of colon cancer: resource-stratified guidelines from the Asian Oncology Summit 2012.

Colon cancer is seen with increasing frequency in the Asia-Pacific region, and it is one of the most important causes of cancer mortality worldwide. This article reviews the available evidence for optimum management of colon cancer-in particular, with respect to screening and early detection of colon cancer, laparoscopic surgical treatment, adjuvant treatment of individuals with high-risk stage II and stage III cancer, palliative treatment of patients with metastatic disease, and management of resectable and potentially resectable metastases-and how these strategies can be applied in Asian countries with different levels of health-care resources and economic development, stratified by basic, limited, enhanced, and maximum resource levels.

Access to cancer medications in low- and middle-income countries

Major breakthroughs have been realized in controlling cancer in the past five decades. However, for patients in low- and middle-income countries (LMICs), many of these advances are nothing but an aspiration and hope for the future. Indeed, the greatest challenge we face in oncology today is how to reconcile small, incremental and significant improvements in the management of cancer with the exponentially increasing costs of new treatments. Emerging economies are attempting to address this important issue of access to cancer medications. In this Review, we examine how LMICs are using generic and biosimilar drugs, expanding participation in clinical trials, implementing universal health-care schemes to pool resources, and using compulsory licensing schemes as well as increasing multiple-stakeholder public–private partnerships to increase access to cancer medications for their citizens. Any truly effective programme will require multiple stakeholder involvement—including governments, industry and civil society—to address the issue of access to medication. Only with the creation of a global entity to fight cancer that is supported by a global fund—for example, in the mould of the GAVI alliance and the International Finance Facility for Immunization—will we truly be able to improve cancer care in LMICs and drive down the high mortality rates in these regions.

Bevacizumab in the Treatment of Metastatic Breast Cancer: Friend or Foe?

Metastatic breast cancer (MBC) is a major cause of death among women worldwide. Progress has been made in treating MBC with the advent of anti-estrogen therapies, potent cytotoxic agents, and monoclonal antibodies. Bevacizumab is a monoclonal antibody against circulating vascular endothelial growth factor (VEGF), which was approved in 2008 by the US Food and Drug Administration (FDA), for first-line treatment of HER-2 negative MBC in combination with paclitaxel. The FDA then reversed this decision in December 2010 by recommending removal of the MBC indication from bevacizumab, citing primarily safety concerns, and that these risks did not outweigh the ability of bevacizumab to significantly prolong progression-free survival. This decision was unexpected in the oncology community and remains controversial. This review looks at all available phase 3 data with bevacizumab in the MBC setting to determine whether the data support this decision by the FDA, and discusses the future of bevacizumab in breast cancer.