Чувствительность первично-множественного синхронного двустороннего рака молочных желез к неоадъювантной химиотерапии

Objective — to evaluate the sensitivity of multiple primary bilateral synchronous breast cancer (BC) to neoadjuvant drug therapy. Subject and methods. The investigation enrolled 14 patients with multiple primary synchronous BC who received drug treatment at the first stage of combined treatment. Eleven patients underwent 6 to 8 cycles of neoadjuvant polychemotherapy (NAPCT); targeted therapy drugs were simultaneously added to taxane-containing regimens in 2 patients with HER2-positive tumors. Results. The mean age of the patients was 44.3±13.8 years, which was substantially younger than that of the total population of BC patients. The histological pattern of tumor nodules in both mammary glands was the same in 11 patients and the tumors in the mammary glands were different in 3 patients. Therapeutic pathomorphism (TP) was absent in 2 (8.3%) cases; it was poorly expressed (grade 1) in 4 (12.5%) cases, grades 2, 3, and 4 were seen in 7 (29.2%), 6 (16.7%), and 9 (33.3%), respectively. None of the 7 patients with the edematous-infiltrative form of BC achieved grade 4 TP despite its different biological types. The immunohistochemical study showed that edematous infiltrative BC was presented as a luminal type in 5 cases, as a triple-negative one in 1 case, and as a luminal type B, HER2-positive in 1 case. Nine of the 28 cases achieved complete TP in the primary tumor, but only one patient had it in both tumors with different biological types. Conclusion. In most cases, the reaction of synchronous tumors to NAPCT did not coincide in the same patient. A complete pathomorphism was most common in the triple negative type (33.3±16.6%), which corresponds to the current ideas on the behavior of this aggressive biological type of BC. The authors consider it necessary to further study the reaction of synchronous tumors to neoadjuvant therapy and to accumulate clinical materials for the reliable confirmation of the findings, which is important for the development of an adequate treatment policy and theoretical knowledge of the pathogenesis of drug sensitivity/resistance of breast tumors.Цель исследования — оценить чувствительность первично-множественного двустороннего синхронного рака молочных желез (РМЖ) к неоадъювантной лекарственной терапии. Материал и методы. В исследование включили 14 пациенток с первично-множественным синхронным РМЖ, которые на I этапе комбинированного лечения получили лекарственное лечение. У 11 больных проведено от 6 до 8 курсов неоадъювантной полихимиотерапии (НАПХТ), у 2 с НER2-позитивными опухолями одновременно к таксансодержащим режимам добавляли препараты таргетной терапии. Результаты. Средний возраст больных составил 44,3±13,8 года, что существенно меньше по сравнению с общей популяцией больных РМЖ. Гистологическая форма опухолевых узлов у 11 пациенток была одинаковой в обеих молочных железах, у 3 опухоли в молочных железах отличались. Лечебный патоморфоз (ЛП) отсутствовал в 2 (8,3%) случаях, был слабо выражен (I степень) в 4 (12,5%), II степень была в 7 (29,2%), III степень — в 6 (16,7%), IV степень — в 9 (33,3%) случаях. Из 7 пациенток с отечно-инфильтративной формой РМЖ ни у одной не был достигнут ЛП IV степени, несмотря на его различные биологические типы. По данным ИГХ-исследования отечно-инфильтративный РМЖ в 5 случаях был представлен люминальным типом, в 1 случае — тройным негативным и в 1 — люминальным типом В, HER2-позитивным. Полный ЛП в первичной опухоли был достигнут в 9 из 28 случаев, но лишь у одной пациентки в обеих опухолях с различными биологическими типами. Заключение. Реакция синхронных опухолей у одной и той же больной на НАПХТ в большинстве случаев не совпадала. Наиболее часто полный патоморфоз отмечен при тройном негативном типе (33,3±16,6%), что соответствует современным представлениям о поведении этого агрессивного биологического типа РМЖ. Мы полагаем, что необходимо дальнейшее изучение особенностей реакции синхронных опухолей на неоадъювантное воздействие, накопление клинического материала для достоверного подтверждения полученных данных, что важно для выработки адекватной тактики лечения и наработки теоретических знаний патогенеза лекарственной чувствительности/резистентности опухолей молочной железы

Адъювантная и неоадъювантная химиогормонотерапия у больных с наличием метастазов в лимфатических узлах и олигометастазов в костях скелета при раке предстательной железы высокого риска прогрессирования. Собственный опыт

Prostate cancer is one of the leading in the structure of oncological morbidity in men. Currently in the treatment of prostate cancer with the presence of metastases in the lymph nodes and oligometastases in the bones of the skeleton chemo-hormonotherapy is used. The tolerability of this therapy has not yet been fully studied. In our work we showed that this method of treatment in this category of patients is low-toxic. The main manifestations of toxicity were hematologic and gastrointestinal toxicity, but they did not exceed of the III degree.Рак предстательной железы (РПЖ) является одним из ведущих в структуре онкологической заболеваемости у мужчин. В настоящее время при лечении РПЖ с наличием метастазов в лимфатических узлах и олигометастазов в костях скелета используют химиогормонотерапию, переносимость которой еще не до конца изучена. В нашей работе показано, что этот метод лечения у данной категории больных является малотоксичным. Основными проявлениями токсичности явились гематологическая и гастроинтестинальная, однако они не превышали степень I-II

Rational sequence of monoclonal antibodies in the treatment of non-resectable head and neck squamous cell carcinoma [Рациональная последовательность моноклональных антител в лечении нерезектабельного плоскоклеточного рака головы и шеи]

This article discusses current approaches to first-line chemotherapy for non-resectable head and neck squamous cell carcinoma and describes factors affecting the choice of treatment regimen according to the results of randomized clinical trials. we provide a rationale for creating a long-term strategy of chemotherapy in different clinical situations. we also report two cases of concomitant administration of cetuximab and platinum-based therapy as an example of high efficacy of monoclonal antibodies. © 2022 Farmatsiya i Farmakologiya. All rights reserved

Neoadjuvant chemohormonal therapy and radical prostatectomy in a patient with lymphogenic metastatic prostate cancer

Prostate cancer (PC) is now one of the most common malignancies among men. Radical prostatectomy is the most commonly used therapy option for patients with localized PC. The appropriateness of surgical treatment for locally advanced and lymphogenic metastatic PC remains controversial, as the probability of non-radical intervention increases significantly and the risk for disease progression becomes higher. At the same time, interest in surgical treatment in patients with PC at high risk of progression, including those with lymphogenic metastases has recently increased greatly. There are more and more studies demonstrating improved survival rates in patients with high-risk PC, including those with distant metastases, who have undergone radical prostatectomy and lymphadenectomy compared with a cohort of patients who have received only drug therapy In addition to the studies evaluating the efficiency of neoadjuvant therapy before surgery in patients with localized or locally advanced high-risk PC, there are also investigations considering this option in PC patients with lymphogenic metastases. The paper gives the results of a clinical observation that shows the high efficiency of a multimodal approach with neoadjuvant chemohormonal therapy, followed by surgical treatment in a patient with lymphogenic metastatic PC

Neoadjuvant and adjuvant chemohormonal therapy in patients with high-risk and very high-risk prostate cancer: Our experience

Background. The approach to the management of prostate cancer with lymph node metastases has recently moved towards aggressive multi-modal treatment with the use of the most rational combinations that are currently available. Objective: to assess the efficacy and tolerability of chemohormonal therapy (CHT) in patients with high-risk and very high-risk prostate cancer. Materials and methods. An open prospective clinical trial evaluating the efficacy and tolerability of neoadjuvant and adjuvant CHT in patients with high-risk and very high-risk prostate cancer was initiated in 2016 at the P.A. Herzen Moscow Oncology Research Institute. Patient recruitment is still ongoing. A total of 64 patients with high-risk and very high-risk prostate cancer (сT3N0-T3N+М0, prostate specific antigen (PSA) ≥20 ng/mL, and Gleason score of 8-10) were recruited since July 2016. All patients were examined prior to treatment initiation and after 3 and 6 courses of therapy. The examination included pelvic magnetic resonance imaging, ultrasound imaging of the abdominal cavity and retroperitoneal space, transrectal ultrasound imaging, and chest radiography or computed tomography. Serum PSA level was evaluated before each course of therapy. Bone scintigraphy was performed before treatment and after its completion. Study participants were divided into two groups. Group A included patients that initially underwent surgical treatment and then 6 courses of CHT no later than 6 weeks after surgery: docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle and oral prednisolone 10 mg/day. Patients also received hormonal therapy with luteinizing hormone-releasing hormone analogue (aLHRH) given in depot injections every 28 days. Group B included patients that initially received 6 courses of CHT: docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle and oral prednisolone 10 mg/day. After that, patients underwent radical prostatectomy with pelvic lymphadenectomy no later than 4 weeks after the completion of chemotherapy. Patients also received hormonal therapy with aLHRH given in depot injections every 28 days. The total treatment duration was 6 months. Results. The group of adjuvant CHT included 24 patients with high-risk prostate cancer (T3b-4N+М0 with at least 5 regional lymph node metastases detected by morphological examination of surgical specimens). All patients had Gleason score 8-10 tumors. Mean age of patients was 63.0 ± 7.7 years (range: 46-72 years). In total, all patients received 142 courses of CHT. By the time of publishing this article, 23 (96 %) of patients completed their treatment. The group of neoadjuvant CHT included 40 patients with very high-risk prostate cancer (T3b-4N+М0 with metastases to pelvic and retroperitoneal lymph nodes detected by instrumental examination). All patients had Gleason score 8-10 tumors. Mean age of patients was 61.0 ± 6.4 years (range: 43-69 years). In total, all patients received 236 courses of CHT. By the time of publishing this article, 36 (90 %) of patients completed their treatment. Thirty-five patients (87 %) underwent radical prostatectomy with extensive pelvic and paraaortic lymphadenectomy. Routine pathological examination demonstrated that all patients had signs of tumor destruction. Thirty-three participants (94 %) had grade II therapeutic pathomorphosis, whereas 2 patients (6 %) had grade III therapeutic pathomorphosis. Median PSA relapse-free survival (PSA-RFS) rate in the neoadjuvant CHT group was 10 months. Serum PSA of 0.1 ng/mL 1 month postop-eratively correlated with longer RFS (р = 0.04). Biochemical relapse (PSA level >0.2 ng/mL) was observed in 6 patients (15 %) from this group. Later these patients received hormonal therapy with aLHRH. Median PSA-RFS in the adjuvant CHT group was 11 months. The main adverse events in the two groups were hematological toxicity, observed in 24 patients (34.29 %), and gastrointestinal toxicity, observed in 9 patients (12.86 %) (diarrhea (n = 6) and stomatitis (n = 3)). Only grade I-II toxicity was registered so far. Two patients (3.1 %) had febrile neutropenia, which required cytostatic dose reduction by 20 %. Relatively good tolerability and acceptable quality of life allowed the vast majority of patients to be treated on an outpatient basis. Conclusion. So far, we can make only a preliminary conclusion that adjuvant and neoadjuvant CHT is a promising treatment strategy for high-risk and very high-risk prostate cancer. © ABC-press Publishing House. All rights reserved

Neoadjuvant chemohormonal therapy and radical prostatectomy in a patient with lymphogenic metastatic prostate cancer

Prostate cancer (PC) is now one of the most common malignancies among men. Radical prostatectomy is the most commonly used therapy option for patients with localized PC. The appropriateness of surgical treatment for locally advanced and lymphogenic metastatic PC remains controversial, as the probability of non-radical intervention increases significantly and the risk for disease progression becomes higher. At the same time, interest in surgical treatment in patients with PC at high risk of progression, including those with lymphogenic metastases has recently increased greatly. There are more and more studies demonstrating improved survival rates in patients with high-risk PC, including those with distant metastases, who have undergone radical prostatectomy and lymphadenectomy compared with a cohort of patients who have received only drug therapy In addition to the studies evaluating the efficiency of neoadjuvant therapy before surgery in patients with localized or locally advanced high-risk PC, there are also investigations considering this option in PC patients with lymphogenic metastases. The paper gives the results of a clinical observation that shows the high efficiency of a multimodal approach with neoadjuvant chemohormonal therapy, followed by surgical treatment in a patient with lymphogenic metastatic PC

Неоадъювантная и адъювантная химиогормонотерапия у пациентов с раком предстательной железы высокого риска прогрессирования

Prostate cancer (PC) is an actual disease and a frequent oncological pathology in men. The detection rate of locally advanced and lymphogenic disseminated forms of prostate cancer in Russia remains high. Therapeutic tactics in PC patients is determined by the prevalence of the tumor process, the stage of the disease, and belonging to a risk group. In patients with a high and extremely high risk of disease progression, a multimodal approach can be considered. To date, there are many studies on neoadjuvant therapy, and there are also a number of works on adjuvant drug treatment. Neoadjuvant chemohormonotherapy at the first stage as part of a conditionally combined treatment demonstrates the advantage of this approach. Regarding the use of adjuvant chemotherapy, the data are contradictory. Further research is required to understand the appropriateness of this treatment approach. In the near future, probably, a multimodal approach to the treatment of patients of this cohort will be included in the standards of antitumor therapy.Рак предстательной железы (РПЖ) является актуальным заболеванием и частой онкологической патологией у мужчин. Выявление местнораспространенных и лимфогенно-диссеминированных форм РПЖ в России остается высоким. Лечебная тактика у больных РПЖ определяется распространенностью опухолевого процесса, стадией заболевания и принадлежностью к группе риска. У пациентов с высоким и крайне высоким риском прогрессирования заболевания может рассматриваться применение мультимодального подхода. На сегодняшний день имеется много исследований, посвященных неоадъювантной терапии, также есть ряд работ, посвященных адъювантному лекарственному лечению. Проведение на первом этапе неоадъювантной химиогормонотерапии в рамках условно-комбинированного лечения демонстрирует преимущество данного подхода. В отношении использования адъювантной химиотерапии данные противоречивы. Необходимо проведение дальнейших исследований для понимания целесообразности данного лечебного подхода. Возможно, в ближайшем будущем применение мультимодального подхода к лечению пациентов указанной когорты войдет в стандарты противоопухолевой терапии

Eribulin-trastuzumab combination in HER2-positive metastatic breast cancer: updated results from a Russian observational study

Introduction. The standard of 1st line treatment of HER2+ metastatic breast cancer (mBC) is double blockade with trastuzumab and pertuzumab + taxane, 2nd line – Trastuzumab-emtazine. There are no standards for further treatment, as well as the optimal drug sequence. Expansion of the arsenal of therapeutic possibilities and the use of new combinations will certainly improve the results of treatment of this category of patients and increase their life expectancy. Aim. We sought to describe treatment patterns of eribulin and clinical outcomes of metastatic HER2-positive breast cancer treated with eribulin plus trastuzumab combination in academic institutions and community oncology practices across the Russian Federation. Materials and methods. Patients treated with eribulin anytime between Jan, 2014 and Sep, 2019 with a diagnosis of MBC were identified by 23 providers from Russia. Providers retrospectively reviewed the health records and abstracted selected data points into an electronic case report form for each eligible patient. Results. 100 HER2-positive pts received eribulin in combination with trastuzumab. Median age was 55 (31–80) yrs and ECOG status 0–3. 67% pts had visceral metastases. Eribulin was administered as 1st and 2nd line to 23 (23%) pts, 3rd line to 31 (31%) pts, 4th line and later to 46 (46%). Median number of cycles was 5 (2–27). ORR was 12%, SD – 72%, SD > 6 months – 23%, PD – 16%. Clinical efficacy rate achieved in 35%. Median PFS was 5.07 months (95% CI 4.021–6.119). According to the ER-status the response to eribulin and trastuzumab was different. ORR was 18.8%, SD 72.9% in pts with ER-positive MBC (n = 48) and 5.8% and 71.2% respectively in ER-negative MBC (n = 52). Median PFS was 6.97 months (95% CI 3.924–10.016) in pts with ER-positive MBC and 4.67 months (95% CI 3.841–5.499) in ER-negative MBC (р = 0.3). The combination was well tolerated: dose reductions were required in 12% pts, withdrawal due to toxicity in 4% pts. The most common type of toxicity was hematological with neutropenia Gr III-IV in 14 (14%) pts. Peripheral neuropathy Gr III was observed in 5 (5%) pts. No cardiotoxicity was detected. Conclusions. This is the real-life data of clinical outcomes for patients receiving eribulin plus trastuzumab for HER2-positive MBC throughout the Russian Federation. Our experience with eribulin plus trastuzumab demonstrates that this combination may be a potential effective treatment option for HER-2 positive MBC patients