Angélica Nogueira-Rodrigues

Progress and remaining challenges for cancer control in Latin America and the Caribbean

Cancer is one of the leading causes of mortality worldwide, and an increasing threat in low-income and middle-income countries. Our findings in the 2013 Commission in The Lancet Oncology showed several discrepancies between the cancer landscape in Latin America and more developed countries. We reported that funding for health care was a small percentage of national gross domestic product and the percentage of health-care funds diverted to cancer care was even lower. Funds, insurance coverage, doctors, health-care workers, resources, and equipment were also very inequitably distributed between and within countries. We reported that a scarcity of cancer registries hampered the design of credible cancer plans, including initiatives for primary prevention. When we were commissioned by The Lancet Oncology to write an update to our report, we were sceptical that we would uncover much change. To our surprise and gratification much progress has been made in this short time. We are pleased to highlight structural reforms in health-care systems, new programmes for disenfranchised populations, expansion of cancer registries and cancer plans, and implementation of policies to improve primary cancer prevention.

Phase I Trial of Erlotinib Combined with Cisplatin and Radiotherapy for Patients with Locally Advanced Cervical Squamous Cell Cancer

Purpose: This phase I trial was aimed to determine the maximum tolerated dose and related toxicity of erlotinib (E) when administered concurrently with standard chemoradiation (CRT) for cervical cancer. Experimental Design: In a modified Fibonacci design, the study aimed to study three cohorts of at least three patients receiving escalating doses of erlotinib (50/100/150 mg) combined with cisplatin (40 mg/m2, weekly, 5 cycles) and radiotherapy (external beam 4,500 cGy in 25 fractions, followed by 4 fractions/600 cGy/weekly of brachytherapy) in squamous cell cervical carcinoma patients, stage IIB to IIIB. Results: Fifteen patients were enrolled, 3 at dose level (DL) 50 mg, 4 at DL 100 mg, and 8 at DL 150 mg. Patients presented median age 47 (36-59), stage IIB (46.2%) and IIIB (53.8%). Overall, E+CRT was well-tolerated. Three patients did not complete the planned schedule. One patient at DL 100 mg withdrew informed consent due to grade 2 rash; at DL 150 mg, 1 patient presented Raynauds Syndrome and had C interrupted, and another patient presented grade 4 hepatotoxicity. The latter was interpreted as dose limiting toxicity and a new cohort of 150 mg was started. No further grade 4 toxicity occurred. Grade 3 toxicity occurred in 6 cases: diarrhea in 3 patients, rash in 2 patients, and leukopenia in 1 patient. E+CRT did not lead to limiting in-field toxicity. Conclusions: E+CRT is feasible to locally advanced squamous cell cervical cancer and is well tolerated. The maximum tolerated dose has been defined as 150 mg. To the best of our knowledge, this is the first report of a combination of erlotinib, cisplatin, and pelvic radiotherapy.

Phase 2 trial of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced cervical cancer

Cisplatin‐based chemoradiation (CRT) is the standard treatment for patients with locally advanced cervical cancer. Epidermal growth factor receptor (EGFR) is frequently overexpressed in cervical cancer, and EGFR inhibition itself has antitumor effects and potentiates CRT. Results of a previous phase 1 trial of the EGFR inhibitor erlotinib combined with cisplatin‐based CRT (E + CRT) recommended a phase 2 erlotinib dose of 150 mg/day.

Cervical cancer control in Latin America: A call to action.

Cervical cancer (CC) is second most common cause of cancer in Latin America and is a leading cause of cancer mortality among women. In 2015, an estimated 74,488 women will be diagnosed with CC in Latin America and 31,303 will die of the disease. CC mortality is projected to increase by 45% by 2030 despite human papillomavirus (HPV) vaccination and screening efforts. In this setting, the goal was of the current study was to examine CC control efforts in Latin America and identify deficiencies in these efforts that could be addressed to reduce CC incidence and mortality. The authors found that HPV vaccination has been introduced in the majority of Latin American countries, and there is now a need to monitor the success (or shortcomings) of these programs and to ensure that these programs are sustainable. This topic was also reviewed in light of emerging data demonstrating that visual inspection with acetic acid and HPV DNA testing without Papanicolaou tests have efficacy from a screening perspective and are good alternatives to cytology‐based screening programs. Overall, there is a need to build capacity for CC control in Latin America and the best strategy will depend on the country/region and must be tailored to meet the needs of the population as well as available resources. Cancer 2016;122:502–514.

First-line paclitaxel and carboplatin in persistent/recurrent or advanced cervical cancer: a retrospective analysis of patients treated at Brazilian National Cancer Institute.

Objective Cervical cancer represents the third most commonly diagnosed cancer and the fourth cause of cancer death in women worldwide. In the palliative scenario, the combination of paclitaxel and cisplatin is widely used. Carboplatin is also an active agent in cervical cancer, and its association with paclitaxel could represent a well-tolerated, less toxic, and effective therapeutic option. The objective of this study was to evaluate response rate, progression-free survival, overall survival, and toxicity of carboplatin and paclitaxel in first palliative line for cervical cancer. Methods A retrospective search of database at Brazilian National Cancer Institute was performed, and all patients with persistent/recurrent and advanced cervical cancer treated with paclitaxel and carboplatin in first palliative line, between August 2008 and January 2010, were included. Results A total of 153 women were enrolled. Objective responses were documented in 34.6% (5.2% of complete responses and 29.4% of partial responses). With a median follow-up of 27.8 months, the median progression-free survival was 5.2 months, and the median overall survival was 10.63 months. The most common toxicity was myelosuppression: grades 3 and 4 anemia, neutropenia, and thrombocytopenia observed in 43.0%, 17.8%, and 9.2% of the cases, respectively. Neurotoxicity was presented by 30.7% of the patients. Renal toxicity was detected in 21.9% of the patients, but only 4.0% were grade 3, and none were grade 4. Conclusions This retrospective study has demonstrated that paclitaxel-carboplatin is an active and well-tolerated regimen for the treatment of advanced cervical cancer.

Comparison of adenocarcinoma (ACA) and squamous cell carcinoma (SCC) of the uterine cervix in a sub-optimally screened cohort: A population-based epidemiologic study of 51,842 women in Brazil

BACKGROUND Most cancers of the uterine cervix are SCC, but the relative and absolute incidence of ACA has risen in recent years, and ACA now accounts for approximately 20% of invasive cervical cancers in the screened populations worldwide. OBJECTIVE To compare the epidemiological, clinical characteristics, and treatment outcomes of ACA with those of SCC of the cervix in a sub-optimally screened population. METHODS Data from cervical cancer patients with SCC and ACA treated from 2000 through 2009 were obtained from the Brazilian Hospital Cancer Register databases. The summary odds ratios and chi-square tests were estimated. RESULTS A total of 51,842 patients including 45,540 (87.8%) cases of SCC and 6302 (12.2%) of ACA were analyzed. Compared with the ACA patients, the SCC patients were younger and more frequently black and had a higher degree of illiteracy and alcohol and tobacco consumers. The tumor stage at the time of diagnosis was also significantly different between the two groups. However, initial therapeutic response and death rate after the first course of treatment were similar in both groups. CONCLUSIONS Differences between ACA and SCC were observed for all demographic and clinical variables analyzed but not for responses to treatment and death at the end of the first course of treatment. Irrespective of the histological subtype, the quality of screening and treatment must be improved in developing countries, since initial therapeutic response of ACA and SCC is similar.

Systematic Review and Network Meta-Analysis of Bevacizumab Plus First-Line Topotecan-Paclitaxel or Cisplatin-Paclitaxel Versus Non–Bevacizumab-Containing Therapies in Persistent, Recurrent, or Metastatic Cervical Cancer

Objective Despite advances in cervical cancer prevention and diagnosis, outcomes for patients given a diagnosis of advanced and recurrent disease are poor. In the GOG240 trial, the addition of bevacizumab to paclitaxel-topotecan or paclitaxel-cisplatin has been shown to prolong survival compared with paclitaxel-topotecan or paclitaxel-cisplatin in patients with persistent, recurrent, or metastatic disease. However, standards of care vary between regions and countries. The purpose of this systematic review and network meta-analysis was to enable a comparison between bevacizumab + chemotherapy with multiple monotherapy or combination chemotherapy regimens in the treatment for women with advanced, recurrent, or persistent cervical cancer. Methods/Materials A systematic literature review was conducted to identify randomized or nonrandomized controlled trials of patients with recurrent, persistent, or metastatic cervical cancer published in English from 1999 to 2015. A feasibility study was performed to assess the heterogeneity of the trials, and a network meta-analysis was conducted. Fixed- and random-effects models were fitted to calculate the hazard ratio for overall survival (OS) for all pairwise comparisons and ranking of all interventions. Results Twenty-three studies (19 trials) met inclusion criteria and were included in the review. Sample sizes ranged from 69 to 452, and median patient age ranged from 45 to 53 years. There was a trend toward prolonged OS with cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab compared with all non–bevacizumab-containing therapies. Cisplatin-paclitaxel-bevacizumab had the highest probability of being the most efficacious compared with all regimens (68.1%), and cisplatin monotherapy had the lowest (0%). Conclusions The results of this network meta-analysis show that bevacizumab in combination with paclitaxel-topotecan or paclitaxel-cisplatin is likely to prolong OS over other non–bevacizumab-containing chemotherapies (eg, paclitaxel-carboplatin), which were not included in the GOG240 trial. In patients with advanced, persistent, and recurrent cervical cancer, cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab showed the highest efficacy in all regimens investigated in this analysis.

An alert to Latin America: Current human papillomavirus vaccination trends highlight key barriers to successful implementation

&NA; Human papillomavirus vaccine programs run the risk of repeating the problems associated with Papanicolaou testing programs in low‐income and middle‐income countries: an efficient, life‐saving tool that unfortunately is underused for cancer prevention. There is a great need for vigilance in the ongoing implementation of the human papillomavirus vaccine in Latin America.

Disparities in Breast, Lung, and Cervical Cancer Trials Worldwide

Purpose As cancer burden has risen worldwide, physicians, patients, and their advocates have become aware that the clinical cancer trial research paradigm is not ubiquitous. Furthermore, the number and characteristics of trials that are registered in low- and middle-income countries (LMICs) compared with that in high-income countries (HICs) are unknown. Methods We collected retrospective data on trials for breast, lung, and cervical cancer registered in ClinicalTrials.gov or with the WHO International Clinical Trial Registry Platform between 2010 and 2017. The data were then classified as trials within LMICs or HICs using definitions from the World Bank. Results Included in these analyses were 6,710 trials, of which 3,164 (47%) were breast cancer trials, 3,283 (49%) were lung cancer trials, and 263 (4%) were cervical cancer trials. There were 1,951 (29%) trials from LMICs and 4,759 (71%) trials from HICs (P < .001). Although the proportion of phase III trials in HICs versus LMICs was similar (18% v 17%; P = .66), the number of phase I trials in LMICs was significantly lower than that of HICs (20% v 2%; P < .001). For several LMICs with the highest mortality-to-incidence ratios for breast, lung, or cervical cancer, there were no cancer trials registered in the registration data bases searched for this work. Conclusion There are differences in access to cancer clinical trials in LMICs compared with HICs. Several factors, such as excessive cost and a lack of infrastructure and expertise, may explain these differences.

A Rare Presentation of Primary Breast Carcinoma in the Vulva: A Case Report and Literature Review.

Mammary gland carcinoma arising from ectopic mammary tissue in the vulva is an extremely rare occurrence with only 28 cases reported in the literature and carrying an uncertain prognosis.