Real-world data on adjuvant capecitabine after standard neoadjuvant chemotherapy for triple negative breast cancer.

Objective: Neoadjuvant chemotherapy (NACT) has become the standard of care for patients with triple-negative breast cancer (TNBC) with tumors > 1 cm or positive axillary nodes. Pathologic complete response (pCR) has been used as an endpoint to select patients for treatment scaling. This study aimed to examine the benefit of adding adjuvant capecitabine for TNBC patients who did not achieve pCR after standard NACT in a real-world scenario. Methods: This retrospective cohort study included all patients with TNBC who underwent NACT between 2010 and 2020. Clinicopathological data were obtained from the patient records. Univariate and multivariate analyses were conducted at the 5 years follow-up period. Results: We included 153 patients, more than half of whom had stage III (58.2%) and high-grade tumors (60.8%). The overall pCR rate was 34.6%, and 41% of the patients with residual disease received adjuvant capecitabine. Disease-specific survival (DSS) among the patients who achieved pCR was significantly higher (p<0.0001). Residual disease after NACT was associated with detrimental effects on DSS. In this cohort, we did not observe any survival benefit of adding adjuvant capecitabine for patients with TNBC subjected to NACT who did not achieve pCR (p=0.52). Conclusion: Our study failed to demonstrate a survival benefit of extended capecitabine therapy in patients with TNBC with residual disease after NACT. More studies are warranted to better understand the indication of systemic treatment escalation in this scenario.

Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer.

BACKGROUND: Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy-TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW. METHODS: This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)-TNT-arm-or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR). RESULTS: Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns). CONCLUSIONS: TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).

Pembrolizumab para personas menores de 18 años con cáncer colorrectal y metástasis sincrónica abdominoperitoneal irresecable con inestabilidad microsatelital, elegibles para terapia intensiva, quienes progresan a esquemas quimioterápicos que contienen 5-fluorouracilo (5-FU), capecitabina, oxaliplatino e irinotecán / Pembrolizumab for people under 18 years of age with colorectal cancer and irresectable synchronic abdominoperitoneal metastasis with microsatellite instability, eligible for intensive therapy, who progress to chemotherapy regimens containing 5-fluorouracil (5-FU), capecitabine, oxaliplatin and irinotecán

INTRODUCCIÓN: Cuadro clínico: El cáncer colorrectal es una neoplasia maligna del colon o del recto. Según la Organización Mundial de la Salud es la tercera neoplasia más frecuente y la segunda neoplasia con mayor mortalidad. En el año 2020, el Observatorio Global de Cáncer de la Agencia Internacional para la Investigación en Cáncer (GLOBOCAN) reportó 1 931 590 casos nuevos de cáncer colorrectal en todo el mundo y una incidencia estandarizada por edad de 19.6 por 100 000 personas-año. En cuanto a la mortalidad, en todo el mundo se reportó 935 173 muertes atribuibles a cáncer colorrectal y una incidencia de mortalidad estandarizada por edad de 9 por 100 000 personas-año. En América Latina, se reportó un total de 103 954 nuevos casos de cáncer colorrectal, una incidencia estandarizada por edad de 18.5 por 100 000 personasaño, 52 013 muertes atribuibles a cáncer colorrectal y una incidencia de mortalidad estandarizada por edad de 8.9 por 100 000 personas-año. En Perú, para el año 2019, se reporta una prevalencia de cáncer colorrectal de 2.1 por 100 000 y una incidencia de 0.3 por 100 000 entre las personas menores de 20 años. Entre los peruanos con cáncer colorrectal menores de 20 años de edad se reportó 5.04 años de vida saludable perdidos (AVISA) por 100 000 y 0.19 años vividos con discapacidad (AVD) por 100

Photobiomodulation in the treatment of palmar-plantar erythrodysesthesia: a randomised controlled clinical study protocol.

INTRODUCTION: Hand-foot syndrome, also known as palmar-plantar erythrodysesthesia (PPE), is a complication caused by chemotherapy. Clinically, it manifests as erythema and oedema on the palms of the hands and feet, dry and scaly skin, accompanied by a sensation of tightness and pain. Extreme cases have blisters and ulcerations that may require hospitalisation and/or pause in cancer treatment. It can also be accompanied by paraesthesia. Considering the characteristics, photobiomodulation (PBM) may reduce the PPE effects. The objective of this protocol will be to evaluate the efficacy of PBM in reducing PPE induced by capecitabine and 5-fluorouracil chemotherapy. METHODS AND ANALYSIS: This will be a randomised controlled, double-blind, double-centre clinical trial (Centro Asistencial del Sindicato Médico del Uruguay and Instituto Nacional del Cáncer from Uruguay). The sample population (40 individuals) will be divided into two groups: group 1 will receive moisturising cream plus PBM treatment and group 2 moisturising cream plus PBM sham treatment, at the ratio of 1:1. PBM will be performed at 630 nm two times per week in palmoplantar areas of the hands and feet (4 J/cm2), for 4 weeks. The PPE degree and the data referring to the chemotherapy treatment plan will be measured, prior to the start of treatment in the middle and at the end of it. Quality of life questionnaires will be applied at the beginning of the trial and at the end of treatment. The data will be analysed based on the intention-to-treat analysis and α<0.05 will be considered statistically significant. ETHICS AND DISSEMINATION: The protocol was approved by the Research Ethics Committee of Universidad Católica del Uruguay (220316b), of Centro Asistencial del Sindicato Médico del Uruguay (221989) and of Instituto Nacional del Cáncer (2023-04). The recruitment has already started (March 2023). PROTOCOL VERSION: V.2, 27 October 2023. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05337423).

Is there a preferred platinum and fluoropyrimidine regimen for advanced HER2-negative esophagogastric adenocarcinoma? Insights from 1293 patients in AGAMENON-SEOM registry.

BACKGROUND: The optimal chemotherapy backbone for HER2-negative advanced esophagogastric cancer, either in combination with targeted therapies or as a comparator in clinical trials, is uncertain. The subtle yet crucial differences in platinum-based regimens' safety and synergy with combination treatments need consideration. METHODS: We analyzed cases from the AGAMENON-SEOM Spanish registry of HER2-negative advanced esophagogastric adenocarcinoma treated with platinum and fluoropyrimidine from 2008 to 2021. This study focused exclusively on patients receiving one of the four regimens: FOLFOX (5-FU and oxaliplatin), CAPOX (capecitabine and oxaliplatin), CP (capecitabine and cisplatin) and FP (5-FU and cisplatin). The aim was to determine the most effective and tolerable platinum and fluoropyrimidine-based chemotherapy regimen and to identify any prognostic factors. RESULTS: Among 1293 patients, 36% received either FOLFOX (n = 468) or CAPOX (n = 466), 20% CP (n = 252), and 8% FP (n = 107). FOLFOX significantly increased PFS (progression free survival) compared to CP, with a hazard ratio of 0.73 (95% CI 0.58-0.92, p = 0.009). The duration of treatment was similar across all groups. Survival outcomes among regimens were similar, but analysis revealed worse ECOG-PS (Eastern Cooperative Oncology Group-Performance Status), > 2 metastatic sites, bone metastases, hypoalbuminemia, higher NLR (neutrophil-to-lymphocyte ratio), and CP regimen as predictors of poor PFS. Fatigue was common in all treatments, with the highest incidence in FOLFOX (77%), followed by FP (72%), CAPOX (68%), and CP (60%). Other notable toxicities included neuropathy (FOLFOX 69%, CAPOX 62%), neutropenia (FOLFOX 52%, FP 55%), hand-foot syndrome in CP (46%), and thromboembolic events (FP 12%, CP 11%). CONCLUSIONS: FOLFOX shown better PFS than CP. Adverse effects varied: neuropathy was more common with oxaliplatin, while thromboembolism was more frequent with cisplatin.

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma.

PURPOSE: To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). METHOD AND MATERIALS: All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8 years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. RESULTS: ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5 days, P = 0.042) than in the MF group. CONCLUSION: The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC.

Capecitabine Plus Aromatase Inhibitor as First Line Therapy for Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer.

(1) Background: recent evidence suggests that long low-dose capecitabine regimens have a synergistic effect with endocrine therapy as aromatase inhibitors (AIs), and might increase overall survival for hormone-receptor-positive, HER2-negative, metastatic breast cancer compared to both treatments. We performed a retrospective study to confirm the efficacy and expand the safety data for capecitabine plus AI (a combination henceforth named XELIA) for this indication. (2) We conducted a single-center retrospective cohort study of 163 hormone receptor-positive metastatic breast cancer patients who received either the XELIA regimen, capecitabine, or an aromatase inhibitor (AI) as single agents in first-line treatment. The primary endpoint was progression-free survival, and the secondary endpoints were overall survival, best objective response, and toxicity incidence. (3) Results: the median progression-free survival for patients receiving XELIA, AI, and capecitabine was 29.37 months (20.91 to 37.84; 95% CI), 20.04 months (7.29 to 32.80; 95% CI) and 10.48 (8.69 to 12.28; 95% CI), respectively. The overall response rate was higher in the XELIA group (29.5%) than in the AI (14.3%) and capecitabine (9.1%) groups. However, the differences in overall survival were not statistically significant. Apart from hand-foot syndrome, there were no statistically significant differences in adverse events between the groups. (4) Conclusions: this retrospective study suggests that progression-free survival and overall response rates improved with the XELIA regimen compared to use of aromatase inhibitors and capecitabine alone. Combined use demonstrated an adequate safety profile and might represent an advantageous treatment in places where CDK 4/6 is not available. Larger studies and randomized clinical trials are required to confirm the effects shown in our study.

Epothilones as Natural Compounds for Novel Anticancer Drugs Development.

Epothilone is a natural 16-membered macrolide cytotoxic compound produced by the metabolism of the cellulose-degrading myxobacterium Sorangium cellulosum. This review summarizes results in the study of epothilones against cancer with preclinical results and clinical studies from 2010-2022. Epothilone have mechanisms of action similar to paclitaxel by inducing tubulin polymerization and apoptosis with low susceptibility to tumor resistance mechanisms. It is active against refractory tumors, being superior to paclitaxel in many respects. Since the discovery of epothilones, several derivatives have been synthesized, and most of them have failed in Phases II and III in clinical trials; however, ixabepilone and utidelone are currently used in clinical practice. There is robust evidence that triple-negative breast cancer (TNBC) treatment improves using ixabepilone plus capecitabine or utidelone in combination with capecitabine. In recent years innovative synthetic strategies resulted in the synthesis of new epothilone derivatives with improved activity against refractory tumors with better activities when compared to ixabepilone or taxol. These compounds together with specific delivery mechanisms could be developed in anti-cancer drugs.

Capecitabine-induced oral mucosal hyperpigmentation associated with hand-foot syndrome - A literature review.

BACKGROUND: Capecitabine (Xeloda®) is a cytotoxic, antimetabolite chemotherapeutic agent. Its most common adverse events are diarrhea, hand-foot syndrome (HFS), hyperbilirubinemia, hyperpigmentation, fatigue, abdominal pain, and other gastrointestinal effects. HFS or palmar-plantar erythrodysesthesia (PPE) is an adverse reaction resulting from therapy with chemotherapeutic agents, classified into three degrees. Hyperpigmentation, as an adverse effect of capecitabine, can occur in different locations and with different patterns. The skin, nails and oral mucosal membrane can be affected. OBJECTIVE: The objective of this study was to report and discuss oral hyperpigmentation associated with HFS caused by the use of capecitabine, which is still poorly described in the literature. METHODOLOGY: A literature review was carried out using the online databases PubMed, Scielo, BVS, Lilacs, Medline, BBO and Google Scholar, associating the descriptors "Capecitabine", "Pigmentation Disorders", "Oral mucosa", "Cancer" and "Hand-Foot Syndrome", which were related and used to exemplify, discuss and report the exposed clinical case. RESULTS: This case report corroborates the literature regarding the incidence in females and black skin persons like this patient who was affected by HFS when undergoing antineoplastic therapy with capecitabine and presented hyperpigmentation of the hands, feet and oral mucosa. On the oral mucosa, the hyperpigmented spots were diffuse, showing a blackish color and irregular edges. Their pathophysiology remains unknown. STUDY LIMITATIONS: Few articles citing capecitabine-associated pigmentation. CONCLUSIONS: It is hoped that this study may contribute to the identification and correct diagnosis of hyperpigmentation in the oral cavity, as well as call attention to the adverse effects related to capecitabine.

Management of early-stage triple-negative breast cancer: recommendations of a panel of experts from the Brazilian Society of Mastology.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogenous subtype involving different patterns of behavior and clinical course, demanding a complex, individualized sequence of treatment. The knowledge and attitudes of the affiliated members of the Brazilian Society of Mastology regarding TNBC were evaluated and a consensus regarding management and treatment was reached. METHODS: Affiliates completed a survey involving 44 objective questions. In addition, a specialist meeting was held with 27 experts and 3 ad hoc consultants. The panelists completed the survey before and after brainstorming. Answers achieving 70% of agreement were considered consensual. The chi-square test was used to compare answers between panelists and affiliates and the Kappa coefficient to calculate agreement. RESULTS: Consensus among the panelists increased from 26 (59.1%) to 32 questions (72.7%) following brainstorming (p = 0.17), including 7/10 questions on systemic treatment. Among the affiliates, consensus was achieved for 24 questions (54.5%), resulting in moderate agreement (κ = 0.445). Neoadjuvant chemotherapy should be indicated for almost all cases (except cT1a-b N0) and should include platinum agents. When indicated, immunotherapy is part of the standard of care. The panel reaffirmed the concept of no ink on tumor as indicative of adequate margins and the possibility of sentinel lymph node biopsy for cN1 patients who become cN0 following neoadjuvant therapy. Controversies remain on combining immunotherapy with capecitabine/olaparib in pertinent cases. CONCLUSION: Expert consensus was achieved for > 70% of the questions, with moderate agreement between panelists and affiliates. Educational interventions on systemic breast cancer treatment affected decision-making in 60% of the questions.

Management of patients with early-stage triple-negative breast cancer following pembrolizumab-based neoadjuvant therapy: What are the evidences?

New therapy options have changed the treatment landscape of early-stage triple-negative breast cancer (TNBC) in recent years. Most patients are candidates for neoadjuvant chemotherapy, which helps to downstage the tumor and tailor adjuvant systemic therapy based on pathologic response. Capecitabine, pembrolizumab, and olaparib have been incorporated into the armamentarium of adjuvant treatment for selected patients. The KEYNOTE-522 trial, that demonstrated the benefit of pembrolizumab, given in addition to neoadjuvant chemotherapy and adjuvantly after surgery, represented a paradigm shift for early-stage TNBC treatment. Pembrolizumab was continued in the adjuvant setting irrespective of response to neoadjuvant therapy, and other adjuvant therapies were not administered in the trial. Many questions were then raised on the selection of adjuvant therapy regimens for patients with residual disease (RD). Prior to the routine use of immune-checkpoint inhibitors (ICI), the value of adjuvant capecitabine for patients with RD after neoadjuvant polychemotherapy was demonstrated. Given the poor prognosis of some patients with RD after neoadjuvant chemo-immunotherapy, while the survival advantage of adding capecitabine during the adjuvant phase of pembrolizumab is unknown, it does appear safe and can be considered. Regarding patients harboring germline BRCA mutations with RD after neoadjuvant ICI-containing regimens, the combination of olaparib with pembrolizumab can be an option based on existing safety data.

Oral hyperpigmentation as an initial clinical aspect of hand foot syndrome.

Hand-foot syndrome (HFS) is a common adverse effect of anticancer therapy. It is known to cause dermatological symptoms including acral erythema and dysesthesia of the palms and soles of the feet, swelling, pain, itching, and scaling. Some drugs, like capecitabine, are known to trigger this condition. However, pigmentation of the oral mucosa is a rare adverse effect. This study aims to report a case of oral mucosa hyperpigmentation caused by capecitabine therapy before the clinical diagnosis of HFS. A 58-year-old female, diagnosed with invasive breast duct carcinoma, had the central nervous system, liver, skin, and lung metastasis, using capecitabine every day for 14 cycles. Oral examination revealed multifocal black macules on the hard palate, bilateral buccal mucosa, gingival mucosa, and dorsum of the tongue. The clinical hypothesis was oral mucosa hyperpigmentation by capecitabine use and only periodic follow-up was necessary. Hyperpigmentation of oral mucosa by capecitabine is a rare consequence of neoplastic therapy and your association with HFS is unclear, and poorly reported. The report of these events is important to alert oncology health teams about the individual tolerance to capecitabine therapy.

Eficacia y seguridad de bevacizumab más capecitabina para el tratamiento de pacientes adultos mayores con cáncer colorrectal metastásico, ECOG 0-2, sin tratamiento previo, no tributario a quimioterapia basada en platino (oxaliplatino) ni irinotecán / Efficacy and safety of bevacizumab plus capecitabine for the treatment of older adult patients with metastatic colorectal cancer, ECOG 0-2, treatment-naïve, not amenable to platinum-based chemotherapy (oxaliplatin) or irinotecan

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Institución de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen que expone la evaluación de la eficacia y seguridad de bevacizumab más capecitabina para el tratamiento de pacientes adultos mayores con cáncer colorrectal metastásico, ECOG 0-2, sin tratamiento previo, no tributario a quimioterapia basada en platino (oxaliplatino) ni irinotecán. Así, el médico Nelson Cuevas Muñoz, especialista en oncología médica del Hospital Nacional Edgardo Rebagliati Martins, siguiendo la Directiva N° 003-IETSIESSALUD-2016, envió al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de uso por fuera del Petitorio Farmacológico de EsSalud el producto farmacéutico producto bevacizumab más capecitabina. ASPECTOS GENERALES: En el Dictamen Preliminar N° 002-SDEPFYOTS-DETS-IETSI-2017 se detallan los aspectos generales del cáncer colorrectal metastásico (CCRM). Brevemente, en Perú, en el 2020, el CCR fue la quinta causa de muerte por cáncer en pacientes mayores de 65 años, con una tasa de muerte estandarizada por edad de 52 muertes por cada 100000 habitantes, y una incidencia ajustada por edad de 95 casos por cada 100000 habitantes (GLOBOCAN, 2020). En Estados Unidos, se ha estimado que el 20 % de los pacientes con CCR presentan enfermedad metastásica (Siegel et al., 2022), y que la sobrevida de cinco años en pacientes con CCRM es del 15 %, siendo la más baja comparada con el CCR localizado o regional (NIH, 2022). METODOLOGÍA: La búsqueda bibliográfica exhaustiva se llevó a cabo con el objetivo de identificar la mejor evidencia disponible sobre la eficacia y seguridad de bevacizumab más capecitabina para el tratamiento de pacientes adultos mayores con cáncer colorrectal metastásico, ECOG 0-2, sin tratamiento previo, no tributario a quimioterapia basada en platino (oxaliplatino) ni irinotecán. La búsqueda bibliográfica se realizó en las bases de datos PubMed, The Cochrane Library y LiLACS. Adicionalmente, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas, evaluaciones de tecnologías sanitarias y guías de práctica clínica, tales como: The National Institute for Health and Care Excellence (NICE), The National Comprehensive Cancer Network (NCCN), The European Society for Medical Oncology (ESMO), The American Society of Clinical Oncology (ASCO), The Canadian Agency for Drugs and Technologies in Health (CADTH), Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), Scottish Intercollegiate Guidelines Network (SIGN), Institute for Quality and Efficiency in Health Care (IQWiG), Scottish Medicines Consortium (SMC), Haute Autorité de Santé (HAS), lnstitute for Clinical and Economic Review (ICER), Agency for Healthcare Research and Quality's (AHRQ), National Health and Medical Research Council (NHMRC), New Zealand Guidelines Group (NZGG), Canadian Medical Association (CMA), American College of Physicians Clinical Practice Guidelines, Registered Nurses Association of Ontario (RNAO), y Comissáo nacional de incorporagáo de tecnologías no sus (CONITEC). Adicionalmente, se realizó una búsqueda manual en las bases The Guidelines International Network (G-I-N), el portal de la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), y el repositorio institucional de la Dirección General de .... V Medicamentos, Insumos y Drogas (DIGEMID). Finalmente, se realizó una búsqueda ... A manual en el portal ClinicalTrials.govdel National Institutes of Health (NIH) para identificar ensayos clínicos en desarrollo o que aún no hayan sido publicados. RESULTADOS: Luego de la búsqueda bibliográfica, se incluyeron seis GPC elaboradas por The Cancer Council Australia Colorectal Cancer Guidelines Working Party (CCACCGWP) (Nott et al., 2017), ASCO (Chiorean et al., 2020), The Japanese Society for Cancer of the Colon and Rectum (JSCCR) (Hashiguchi et al., 2020), SIGN (SIGN, 2016), y la NCCN, que elaboró dos GPC, una para pacientes con cáncer de colon (NCCN, 2022a) y otra para pacientes con cáncer rectal (NCCN, 2022b). Además, se incluyó una ETS elaborada por CADTH (CADTH, 2015), y el ECA de fase III, denominado AVEX (Cunningham et al., 2013). CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación no aprueba el uso de bevacizumab más capecitabina para el tratamiento de pacientes adultos mayores con cáncer colorrectal metastásico, ECOG 0-2, sin tratamiento previo, no tributario a quimioterapia basada en platino (oxaliplatino) ni irinotecán.

Quality of life in a randomized trial comparing two neoadjuvant regimens for locally advanced rectal cancer-INCAGI004.

BACKGROUND: Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC), but the emergence of different drug regimens may result in different response rates. Good clinical response translates into greater sphincter preservation, but quality of life (QOL) may be impaired after treatment due to chemoradiotherapy and surgical side effects. OBJECTIVE: To prospectively evaluate the impact of clinical response and surgical resection on QOL in a randomized trial comparing two different neoCRT regimens. METHODS: Stage II and III rectal cancer patients were randomized to receive neoCRT with either capecitabine (group 1) or 5-Fu and leucovorin (group 2) concomitant to long-course radiotherapy. Clinical downstaging was accessed using MRI 6-8 weeks after treatment. EORTCs QLQ-C30 and CR38 were applied before treatment (T0), after neoCRT (T1), after rectal resection (T2), early after adjuvant chemotherapy (T3), and 1 year after the end of treatment or stoma closure (T4). The Wexner scale was used for fecal incontinence evaluation at T4. A C30SummaryScore (Geisinger and cols.) was calculated to compare QOL results. RESULTS: Thirty-two patients were assigned to group 1 and 31 to group 2. Clinical downstaging occurred in 70.0% of group 1 and 53.3% of group 2 (p = 0.288), and sphincter preservation was 83.3% in group 1 and 80.0% in group 2 (p = 0.111). No significant difference in QOL was detected when comparing the two treatment groups after neoCRT using QLQ-C30. However, the CR38 module detected differences in micturition problems (15.3 points), gastrointestinal problems (15.3 points), defecation problems (11.8 points), and sexual satisfaction (13.3 points) favoring the capecitabine group. C30SummaryScore detected significant improvement comparing T0 to T1 and deterioration comparing T1 to T2 (p = 0.025). The mean Wexner scale score was 9.2, and a high score correlated with symptoms of diarrhea and defecation problems at T4. CONCLUSIONS: QOL was equivalent between groups after neoCRT except for micturition problems, gastrointestinal problems, defecation problems, and sexual satisfaction favoring the capecitabine arm after. The overall QOL using the C30SummaryScore was improved after neoCRT, but decreased following rectal resection, returning to basal levels at late evaluation. Fecal incontinence was high after sphincter preservation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03428529.

Adverse reactions and adherence to capecitabine: A prospective study in patients with gastrointestinal cancer.

INTRODUCTION: Capecitabine is an oral anticancer drug which can cause some adverse reactions and the great challenge for its use is to ensure the medication adherence. The aim of this study was to analyze adverse reactions and adherence to capecitabine in patients with gastrointestinal cancer. METHODS: A prospective study was performed in a tertiary teaching hospital in Brazil. Outpatients undergoing capecitabine treatment for colorectal or gastric cancer were followed for three cycles of treatment. Patient demographic and clinical characteristics data were collected. Adverse reactions were analyzed using Common Terminology Criteria for Adverse Events (CTCAE) v.4. Adherence to capecitabine were evaluated using Morisky-Green and MedTake tests. Statistical analysis was conducted using Chi-square, Fisher's exact and McNemer tests. RESULTS: One hundred and four patients were enrolled in this study, with a mean age was 58.5 ± 10.9 years; 51.0% were men and 51.0% Caucasian. Nausea and diarrhea were the most frequently reported adverse reactions (82.7% and 62.5%, respectively), followed by vomiting (54.8%), fatigue (54.8%), and hand-foot syndrome (53.9%). Nausea and diarrhea were also the most severe adverse reactions. Most patients were adherent to capecitabine in all cycles of treatment using the Morisky-Green test. Adherence increased significantly between cycle 1 and cycle 2 by MedTake test (p < 0.001). Some demographic and clinical characteristics were associated with adverse reactions (e.g., age and nausea, gender and nausea and vomiting) and capecitabine adherence (e.g., marital status and educational level) as well as some adverse reactions were associated with capecitabine adherence (hand-foot syndrome and nausea). CONCLUSIONS: Clinical oncology pharmacists must provide patient information on the correct use of capecitabine, manage adverse reactions, and monitor adherence to treatment. Strategies to prevent non-adherence to capecitabine must be adopted to ensure the success of pharmacotherapy.

Capecitabine induced fingerprint loss: Case report and review of the literature.

INTRODUCTION: Adermatoglyphia is defined as the medical condition clinically diagnosed to those who have a congenital or acquired loss of the epidermal ridges on the fingertips, commonly known as fingerprints. Capecitabine, a fluoropyrimidine, is the treatment of choice in a myriad of tumors and has occasionally been reported to cause adermatoglyphia as a secondary effect upon its use. CASE REPORT: A 52-year-old female patient, diagnosed with stage IV metastatic left breast cancer with extension to bone in late 2011 reported upon biopsy a hormone receptor positive Her2 negative ductal carcinoma. After initial treatment with a combined radiotherapy and chemotherapy palliative treatment, hepatic and lung metastasis progression obliged capecitabine oral intake. In 2018, after two years on the fluoropyrimidine (capecitabine), the patient reported adermatoglyphia. MANAGEMENT & OUTCOME: The patient opted to continue taking the medication, since such treatment was working with no other meaningful side effects. Her last work-up studies continue to show complete lung and liver response with stable bone disease. DISCUSSION: Capecitabine is a common drug in the therapy against metastatic breast cancer due to its manageable safety profile. Hand-foot syndrome is a frequent side effect caused by this drug, with dosage adjustment recommended with progression of symptoms. Recent publications have reported adermatoglyphia as a rare side effect of capecitabine use. Upon further examination through dermatoscopy and biopsy, the patient was evidenced to have lost the epidermal ridges that form fingerprints. A score of 9 on the Naranjo scale confirmed to be a consequence of the administration of capecitabine.