Personalised treatment of non-small-cell lung cancer patients — review of current evidence

The increasing number of scientific reports on the new-generation tyrosine kinase inhibitors and immunological checkpoint inhibitors in the management of patients with non-small-cell lung cancer (NSCLC) results in the necessity of frequent guidelines updating and constant preparing of treatment algorithms by scientific societies. This is accompanied by the continuous search for molecular predictive factors that could allow more personalised treatment and increased therapeutic benefits achieved by patients. Based on current recommendations, patients with mutated EGFR or rearranged ALK genes in advanced NSCLC should begin their treatment with tyrosine kinase inhibitors. The use of these agents within first- and second-line treatment may produce significant improvement of prognosis in selected patients. The improvement of survival may be achieved in patients with central nervous system metastases, who have poor prognosis. The role of immunotherapy increases as well, but negative results of some trials (e.g. MYSTIC or CheckMate 026) indicate difficulties in precise defining of groups of patients with the highest chances of benefit from immunotherapy. In view of the results from some trials (e.g. CheckMate 017, KEYNOTE 021, or PACIFIC), PD-L1 expression is not an optimal biomarker for immunotherapy. Initial results of some studies and retrospective analyses suggest the predictive value of other genetic or molecular abnormalities (e.g. high mutation load in tumour genome, microsatellite instability, or repair mechanism abnormalities). Precise definition of new biomarkers and ensuring the availability of genetic testing appears to be mandatory before widespread use of immunotherapy in clinical practice. Recently published positive results of studies testing new targeted agents, which have high value predictive factors, will probably influence the updates of scientific societies’ guidelines and management algorithms. The aim of this review was to assess possibilities of personalised treatment in patients with advanced NSCLC with the use of new generation tyrosine kinase inhibitors and immune checkpoint inhibitors, in view of new scientific reports.The increasing number of scientific reports on the new-generation tyrosine kinase inhibitors and immunological  checkpoint inhibitors in the management of patients with non-small-cell lung cancer (NSCLC) results in the necessity  of frequent guidelines updating and constant preparing of treatment algorithms by scientific societies. This  is accompanied by the continuous search for molecular predictive factors that could allow more personalised  treatment and increased therapeutic benefits achieved by patients. Based on current recommendations, patients  with mutated EGFR or rearranged ALK genes in advanced NSCLC should begin their treatment with tyrosine kinase  inhibitors. The use of these agents within first- and second-line treatment may produce significant improvement  of prognosis in selected patients. The improvement of survival may be achieved in patients with central nervous  system metastases, who have poor prognosis. The role of immunotherapy increases as well, but negative results  of some trials (e.g. MYSTIC or CheckMate 026) indicate difficulties in precise defining of groups of patients with  the highest chances of benefit from immunotherapy. In view of the results from some trials (e.g. CheckMate 017,  KEYNOTE 021, or PACIFIC), PD-L1 expression is not an optimal biomarker for immunotherapy. Initial results of  some studies and retrospective analyses suggest the predictive value of other genetic or molecular abnormalities  (e.g. high mutation load in tumour genome, microsatellite instability, or repair mechanism abnormalities). Precise  definition of new biomarkers and ensuring the availability of genetic testing appears to be mandatory before  widespread use of immunotherapy in clinical practice. Recently published positive results of studies testing new  targeted agents, which have high value predictive factors, will probably influence the updates of scientific societies’  guidelines and management algorithms. The aim of this review was to assess possibilities of personalised  treatment in patients with advanced NSCLC with the use of new generation tyrosine kinase inhibitors and immune  checkpoint inhibitors, in view of new scientific reports.

Metronomic chemotherapy in non-small-cell lung cancer — current status

Chemotherapy remains a standard treatment of advanced non-small-cell lung cancer. Metronomic chemotherapy – frequent administration of low-dose cytotoxic agents – may be a new option with minimal toxicity. This method may have complex mechanisms of action — the antiangiogenic effects and modulation of the immune system are crucial. Vinorelbine could be an option for non-small-cell lung cancer patients because of it has favourable safety profile and the oral form of the drug is easy to administer. There are some studies documenting the clinical activity of oral vinorelbine in advanced non-small-cell lung cancer patients. However, further prospective studies are necessary to assess the place of metronomic chemotherapy in clinical practice

Advanced solitary fibrous tumour of the pleura — a case report and literature review

The solitary fibrous tumour (SFT) is a rare tumour, which usually occurs in the pleura. Patients with an advanced SFT have a poor prognosis. The treatment options for recurrent disease are especially limited. We present the case of a 55-year-old female patient with a malignant SFT of the pleura, who received conventional chemotherapy and targeted therapy. This paper focuses on systemic therapy in the treatment of metastatic SFT. The solitary fibrous tumour (SFT) is a rare tumour, which usually occurs in the pleura. Patients with an advanced SFT have a poor prognosis. The treatment options for recurrent disease are especially limited. We present the case of a 55-year-old female patient with a malignant SFT of the pleura, who received conventional chemotherapy and targeted therapy. This paper focuses on systemic therapy in the treatment of metastatic SFT.

ALK, ROS1 and EGFR next-generation tyrosine kinase inhibitors in advanced non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is the most common cancer in men and the second most common in fe- males. In previous years the significance of some molecular disorders in pathogenesis NSCLC was proven and the value of targeted therapies in the treatment of patients was documented. In subjects with abnormalities of EGFR, ALK and ROS1 genes, appropriate tyrosine kinase inhibitors (TKIs) may be used. The use of these drugs in the first and second treatment lines has affected a significant improvement in the prognosis in this subgroup of patients. The article presents mechanisms of action and data on the clinical value of lorlatinib, brigatinib and dacomitinib in the treatment of patients with advanced lung of lung cancer.Non-small-cell lung cancer (NSCLC) is the most common cancer in men and the second most common in fe- males. In previous years the significance of some molecular disorders in pathogenesis NSCLC was proven and the value of targeted therapies in the treatment of patients was documented. In subjects with abnormalities of EGFR, ALK and ROS1 genes, appropriate tyrosine kinase inhibitors (TKIs) may be used. The use of these drugs in the first and second treatment lines has affected a significant improvement in the prognosis in this subgroup of patients. The article presents mechanisms of action and data on the clinical value of lorlatinib, brigatinib and dacomitinib in the treatment of patients with advanced lung of lung cancer

Metronomic chemotherapy in breast cancer

New effective therapies are under development in breast cancer; at the same time attempts are being made to modify the dosage of already available drugs. The major challenge is to treat patients with multiple comorbidities who are not candidates for standard chemotherapy. An alternative for these patients may be a metronomic chemotherapy, which is based on continuous administration of drugs at very low doses every day or in short intervals. This also cause antiangiogenic and immune-modulating effects. The tolerance of the metronomic therapy is better, which improves the patients’ quality of life. More and more data indicate the use of multidrug metronomic regimens in a broader group of breast cancer patients.This article discusses the use of metronomic chemotherapy in patients with metastatic breast cancer, highlighting the most well—established regimens, which should be considered first of all in elderly patients with comorbidities, who do not need a rapid response to therapy. Published data support also the consideration of the use of multi-drug metronomic chemotherapy in wider group of breast cancer patients. The course of research in this approach has been outlined in patients undergoing adjuvant therapy and receiving maintenance treatment in patients with triple negative breast cancer.New effective therapies are under development in breast cancer; at the same time attempts are being madeto modify the schedules of administration and doses of already available drugs. The major challenge is to treatpatients with multiple comorbidities, who are not candidates for standard chemotherapy. An alternative for thesepatients may be a metronomic chemotherapy, which is based on continuous administration of drugs at very lowdoses every day or in short intervals. This also causes antiangiogenic and immune-modulating effects. The toleranceof the metronomic therapy is better, which improves the patients’ quality of life. More and more data indicatethe use of multidrug metronomic regimens in a broader group of breast cancer patients.This article discusses the use of metronomic chemotherapy in patients with metastatic breast cancer and focuseson the best established regimens of potential use as first-line therapy in elderly patients with comorbidities, whodo not need a rapid response to therapy. Published data support also the consideration of the use of multi-drugmetronomic chemotherapy in wider group of breast cancer patients. The course of research in this approachhas been outlined in patients undergoing adjuvant therapy and receiving maintenance treatment in patients withtriple-negative breast cancer

Second-line treatment in non-small cell lung cancer

U około 50% chorych z rozpoznaniem niedrobnokomórkowego raka płuca (NDRP) w stadium zaawansowanym można uzyskać kliniczne korzyści ze stosowania chemioterapii pierwszej linii z udziałem pochodnych platyny, ale u niemal wszystkich chorych ostatecznie dochodzi do progresji choroby. W tym okresie choroby u części chorych może nadal występować zadowalający stan sprawności i możliwe jest rozważenie stosowania aktywnego leczenia. Monoterapia drugiej linii z wykorzystaniem docetakselu lub pemetreksedu stanowi jedną z możliwości leczenia i u starannie dobranych chorych prowadzi do uzyskania okresowego ustąpienia dolegliwości oraz wydłużenia życia w porównaniu z przeżyciem osiąganym w następstwie stosowania wyłącznie aktywnego leczenia objawowego. Erlotynib - drobnocząsteczkowy inhibitor tyrozynowej kinazy - jest również skuteczny u chorych na zaawansowanego NDRP poprzednio poddawanych chemioterapii. Można go stosować w ramach leczenia drugiej linii w przypadkach, w których nie ma możliwości stosowania chemioterapii lub występuje jej nietolerancja, oraz w ramach leczenia trzeciej linii po niepowodzeniu wcześniejszych dwóch linii chemioterapii. Najlepsze leczenie objawowe jest nadal wartościową metodą postępowania u chorych z upośledzoną sprawnością. Wiele zagadnień związanych z leczeniem drugiej linii u chorych na zaawansowanego NDRP wymaga wyjaśnienia (np. optymalny czas leczenia, ponowne stosowanie leków użytych w ramach wcześniejszej chemioterapii, najlepsze wykorzystanie leków celowanych) i konieczne jest przeprowadzenie dalszych badań klinicznych w celu uzyskania poprawy rokowania chorych.Approximately 50% of patients with advanced non-small-cell lung cancer (NSCLC) may achieve clinical benefit with first-line platinum-based chemotherapy, but nearly all of them develop progressive disease. At this stage, some patients may still have an adequate performance status and they are considered for active treatment. Second-line monotherapy with docetaxel or pemetrexed is a therapeutic option and in carefully selected patients it may produce temporary symptom relief as well as modest life prolongation compared to survival time achieved with active symptomatic care alone. Erlotinib - small-molecule tyrosine kinase inhibitor - is also effective in chemotherapy-pretreated patients with advanced NSCLC and may be used as second-line therapy in patients not suitable or intolerant to cytoxic agents or as third-line therapy after failure of second-line chemotherapy. Best supportive care is still a valid option for patients with poor performance status. A number of questions concerning second-line therapy in patients with advanced NSCLC remain to be answered (eg, optimal duration, rechallenge with agents used in first-line, optimal use of targeted therapies) and further clinical research is mandatory to improve outcome of patients

Surgical therapy in cancer in Poland today and tomorrow — commentary

Opracowanie Chirurgiczne leczenie nowotworów w Polsce: dziś i jutro, przygotowane przez prof. dr hab. med. Krzysztofa Hermana — Krajowego Konsultanta w dziedzinie onkologicznej chirurgii — stanowi ważnąwypowiedź na temat systemu organizacji ochrony zdrowia w onkologii oraz realizacji podyplomowego kształcenia. Wypowiedź lekarza chirurga o wieloletnim doświadczeniu w rozpoznawaniu i leczeniu oraz znaczącychosiągnięciach naukowych skłania do przekazania kilku uwag.Opracowanie Chirurgiczne leczenie nowotworów w Polsce: dziś i jutro, przygotowane przez prof. dr hab. med. Krzysztofa Hermana — Krajowego Konsultanta w dziedzinie onkologicznej chirurgii — stanowi ważnąwypowiedź na temat systemu organizacji ochrony zdrowia w onkologii oraz realizacji podyplomowego kształcenia. Wypowiedź lekarza chirurga o wieloletnim doświadczeniu w rozpoznawaniu i leczeniu oraz znaczącychosiągnięciach naukowych skłania do przekazania kilku uwag

Postępy w leczeniu złośliwego międzybłoniaka opłucnej

The incidence of malignant pleural mesothelioma is likely to increase over the next 10-20 years. Although relatively uncommon, it represents a challenge due to still unsatisfatory prognosis. Once diagnosis is made, many years after asbestos exposure, malignant pleural mesothelioma usually tends to remain confined to the hemithorax. However, the locoregional extent of disease is wide and curative resection is feasible very seldom. Moreover, the role of both local treatment modalities (surgery and radiotherapy) is unsettled definitely. Chemotherapy has been disappointing for years. However, very recently it has shown promising activity with the use of new generation antimetabolities. Although each single therapeutic modality has limited value, a combined approach may improve survival and quality of life. This overview is aiming to present current views on the use of different modalities in the treatment of malignant pleural mesothelioma, in particular their integration within combined management.W ciągu następnych 10-20 lat istnieje prawdopodobieństwo wzrostu zachorowalności na złośliwego międzybłoniaka opłucnej. Chociaż nowotwór ten występuje rzadko, stanowi wyzwanie dla lekarzy ze względu na wciąż niezadowalające wyniki leczenia. W chwili ustalenia rozpoznania, po wielu latach ekspozycji na działanie azbestu, złośliwy międzybłoniak opłucnej jest ograniczony do połowy klatki piersiowej. Jednak rozległość nowotworu sprawia, że rzadko jest możliwe całkowite wycięcie zmian. Ponadto rola obydwu metod leczenia miejscowego (chirurgicznego i promieniami) nie jest ostatecznie ustalona. Stosowanie chemioterapii nie przynosiło przez wiele lat zadowalających wyników. Ostatnio uzyskano zachęcające wyniki dotyczące stosowania antymetabolitów nowej generacji. Niezależnie od ograniczonej skuteczności każdej z wymienionych metod stosowanych pojedynczo, terapia skojarzona może wpłynąć na poprawę przeżycia i jakości życia chorych. Celem artykułu jest przedstawienie obecnych poglądów na temat możliwości wykorzystania różnych metod leczenia złośliwego międzybłoniaka opłucnej, szczególnie ich współdziałania w ramach leczenia skojarzonego