Safety and efficacy of P2Et extract from Caesalpinia spinosa in breast cancer patients: study protocol for a randomized double blind phase II clinical trial (CS003-BC).

BACKGROUND: Chemotherapy in breast cancer is effective but can generate significant toxicity and lead to tumor resistance. Joint treatment with standardized plant extracts can be an alternative to improve the response and allow an effective activation of the antitumor immune response that favors recovery in the short and long term. The P2Et extract of Caesalpinia spinosa presents antitumor activity in cells and animal models of breast cancer, improves the tumor microenvironment, and induces activation of the specific immune response against the tumor and is synergistic when used together with anthracyclines, which makes it a good candidate for evaluation in patients. METHODS: Conducted at a single center, this phase II study is a randomized, double-blind, placebo-controlled trial aimed at assessing the safety and efficacy of P2Et extract in patients diagnosed with stage II and III breast cancer, who are eligible for neoadjuvant treatment. The study aims to determine the safety profile at the previously established optimal biological dose from phase I trial while investigating various efficacy outcomes. These outcomes include improvements in quality of life, immunomodulation, metabolic profile, microbiome, as well as clinical indicators such as tumor reduction, disease-free survival, and pathological response, assessed at different stages of the treatment regimen. DISCUSSION: Treatment with the P2Et extract in breast cancer patients is hypothesized to enhance overall well-being, positively influencing their quality of life, while also triggering an antitumor immune response and enhancing immune infiltration. These combined effects have the potential to contribute to improved long-term survival outcomes for patients receiving the phytomedicine alongside neoadjuvant chemotherapy treatment. TRIAL REGISTRATION: This trial was registered in the US National Library of Medicine with identifier NCT05007444. First Registered August 16th, 2021. Last Updated: August 9th, 2022.

Safety Evaluation in Healthy Colombian Volunteers of P2Et Extract Obtained from Caesalpinia spinosa: Design 3+3 Phase I Clinical Trial.

The polyphenol-enriched extract called P2Et derived from Caesalpinia spinosa (C. spinosa) had antitumor and immunomodulatory activities reported in breast cancer, leukemia, and melanoma. The aim of this study was to evaluate the safety and maximum tolerated dose of P2Et extract in Colombian healthy volunteers in a phase 1 clinical trial, open labelled, single-arm, dose-escalation design 3 + 3. Seven healthy volunteers were included; P2Et was administrated in capsules of 600 mg/d for 28 days. Analysis by intention to treat was performed. 4 volunteers showed adverse events and discontinued the intervention. 94.6% of AE were grade 1, and most of AE had a reasonable possibility of a relationship with the P2Et (83.8%). We found that the oral administration of P2Et is safe in healthy humans with a maximum tolerated dose of 600 mg/d. There was no severe toxicity; most of the adverse events were mild, without significant changes in the safety parameters evaluated.

Evaluation of chemotherapy and P2Et extract combination in ex-vivo derived tumor mammospheres from breast cancer patients.

The main cause of death by cancer is metastasis rather than local complications of primary tumors. Recent studies suggest that breast cancer stem cells (BCSCs), retains the ability to self-renew and differentiate to repopulate the entire tumor, also, they have been associated with resistance to chemotherapy and tumor recurrence, even after tumor resection. Chemotherapy has been implicated in the induction of resistant phenotypes with highly metastatic potential. Naturally occurring compounds, especially phytochemicals such as P2Et, can target different populations of cancer cells as well as BCSC, favoring the activation of immune response via immunogenic tumor death. Here, we evaluated the presence of BCSC as well as markers related to drug resistance in tumors obtained from 78 patients who had received (or not) chemotherapy before surgery. We evaluated the ex vivo response of patient tumor-derived organoids (or mammospheres) to chemotherapy alone or in combination with P2Et. A xenotransplant model engrafted with MDA-MB-468 was used to evaluate in vivo the activity of P2Et, in this model P2Et delay tumor growth. We show that patients with luminal and TNBC, and those who received neoadjuvant therapy before surgery have a higher frequency of BCSC. Further, the treatment with P2Et in mammospheres and human breast cancer cell lines improve the in vitro tumor death and decrease its viability and proliferation together with the release of immunogenic signals. P2Et could be a good co-adjuvant in antitumor therapy in patients, retarding the tumor growth by enabling the activation of the immune response.

Plant-based Complementary and alternative medicine used by breast cancerpatients at the Hospital Universitario San Ignacio in Bogotá, Colombia / Uso de medicina alternativa y complementaria basada en plantas, por pacientes con cáncer de seno en el Hospital Universitario San Ignacio en Bogotá, Colombia

Durante este estudio se buscó determinar la frecuencia de uso demedicina alternativa y complementaria (CAM) basada en plantas, enpacientes con cáncer de seno. Se realizó por medio de encuestas enpacientes con cáncer de seno que asistieron a consulta externa al CentroJaveriano de Oncología del Hospital San Ignacio en Bogotá en losmeses de Junio a Diciembre del 2011. De las 404 encuestas aplicadasen mujeres con cáncer de seno, el 57% consumieron algún tipo deCAM para el cáncer de seno y de estos el 76% consumieron plantasmedicinales como el anamú, la sábila, los frutos rojos y la guanábana,entre otros. El 65% de los pacientes tuvieron una percepción positivafrente al consumo de las plantas medicinales y el 57% de los usuariosde terapias basada en plantas, la uso simultáneamente al tratamientoalopático recomendado por el médico oncólogo. Concluimos quela frecuencia de uso de CAM en pacientes con cáncer de seno delCentro Javeriano de Oncología en Bogotá, esta dentro del rangode prevalencia reportado mundialmente, aunque existen diferenciasmarcadas en los tipos y frecuencias de CAM consumidas. La altaproporción de pacientes que usan CAM basada en plantas sindiscutirlo con el médico oncólogo, tiene como consecuencia la faltade evaluación con respecto a los efectos sinérgicos o antagónicos deestas terapias frente al tratamiento alopático del cáncer de mama; asícomo el potencial antitumoral y inmunomodulador real de las plantasusadas de manera tradicional por lo pacientes oncológicos...

The present study estimates the frequencyof the use of plant-based Complementary andAlternative Medicine (CAM) by breast cancer patients.From June to December of 2011, a self-administeredquestionnaire was given to 404 breast cancer patientsreceiving outpatient therapy at the Javeriana OncologyCenter of the Hospital Universitario San Ignacio inBogotá. The prevalence of patient CAM use was 57%,out of which 76% was based on plants like anamú,aloe, red fruits and soursop. Sixty-five percent of thepatients had a positive perception of using medicinalplants and 57% used them simultaneously with theoncologist recommended allopathic treatment. Weconcluded that the frequency of CAM use in breastcancer patients at the Javeriana Oncology Centeris within the prevalence range reported worldwide,despite differences in CAM types and frequencies. Thehigh rates of plant-based CAM use without physicianconsent, brings about the lack of assessment of thesynergic or antagonistic effects of CAM therapieson the allopathic treatment of breast cancer andevaluation of the antitumor and immunomodulatorypotential of the traditionally used plants...

O presente estudo se propôs a avaliar a frequência dautilização de Medicina Alternativa e Complementar (CAM) baseadaem plantas por pacientes com câncer de mama. Um questionário autoadministradofoi dado a 404 pacientes com câncer que frequentarama terapia ambulatória no Centro Javeriano de Oncologia do HospitalUniversitário San Ignacio, em Bogotá entre junho e dezembro de2011. O consumo de algum tipo de CAM por parte dos pacientesfoi de 56%. 76% selecionaram plantas como anamú, aloé , frutosvermelhos e graviola. Os resultados foram que 65% dos pacientestiveram uma percepção positiva de usar plantas medicinais. 57%dos pacientes utilizaram o tratamento alopático simultaneamente.Conclui-se que a freqüência do uso de CAM em pacientes com câncerde mama no Centro Javeriano de Oncologia está dentro da faixade prevalência registrada no mundo, embora com diferenças nostipos de CAM e freqüências. A elevada taxa de pacientes que usamCAM baseada em plantas sem consentimento médico é o resultadoda falta de respeito ou avaliação dos efeitos sinérgicos o antagônicosde terapias CAM contra o câncer da mama, bem como o potencialtratamento alopático antitumoral e imunomoduladora das plantasreais utilizados tradicionalmente...

Cirugia de cancer de seno: pasado y presente y futuro / Surgery for breast cancer

La cirugía constituye uno de los pilares fundamentales del tratamiento del cáncer de seno; las resecciones radicales han disminuido cada vez más y, paralelamente, las alternativas de tratamiento complementario han tomado mucha más fuerza. El siguiente artículo ilustra la evolución en el tiempo de conceptos básicos en la terapia del cáncer mamario y la influencia que estos nuevos conceptos han tenido sobre el tratamiento de las pacientes del Hospital Universitario San Ignacio