Chemotherapy of advanced non small cell lung cancer: effect on survival and symptoms affecting quality of life

Wstęp: W pracy przedstawiono wyniki leczenia 168 chorych z potwierdzonym histologicznie rozpoznaniem niedrobnokomórkowego raka płuca w stopniu IIIB i IV, leczonych w latach 2002–2006 w Klinice Nowotworów Układowych i Uogólnionych Centrum Onkologii, Oddział w Krakowie. Materiał i metody: Stosowano 4 schematy chemioterapii: EP (cysplatyna, etoposid), MVP (mitomycyna C, winblastyna, cysplatyna), PN (cysplatyna, winorelbina) oraz PG (cysplatyna, gemcytabina). Wyniki: Średnie przeżycie chorych leczonych schematem MVP wynosiło 7,8 miesiąca (mediana 4,3 miesiąca), PG - 7,1 miesiąca (mediana 7,3 miesiąca), EP - 10,2 miesiąca (mediana 7,5 miesiąca), a schematem PN - 14,1 miesiąca (mediana 9,8 miesiąca). Różnice mediany przeżyć pozostają na granicy znamienności statystycznej (p = 0,0679). Średni czas do progresji u chorych leczonych schematem MVP wynosił 3,5 miesiąca (mediana 2,6 miesiąca), schematem PG - 5,2 miesiąca (mediana 5,8 miesiąca), EP - 6,6 miesiąca (mediana 5,2 miesiąca) i schematem PN - 6,7 miesiąca (mediana 5,6 miesiąca). Najkrótszy czas do progresji uzyskano u chorych leczonych schematem MVP (p = 0,0039). Zmniejszenie duszności obserwowano u 60% chorych, bólu u 38,7% chorych, a kaszlu u 60% chorych. Poprawy w zakresie krwioplucia nie oceniono ze względu na zbyt małą liczbę chorych, u których ten objaw występował. Nie stwierdzono istotnych statystycznie różnic w zakresie poprawy objawów związanych z chorobą nowotworową w zależności od zastosowanego schematu leczenia. Wnioski: Ze względu na uzyskane wyniki jako standard leczenia w tej grupie chorych można polecić schemat cysplatyna + winorelbina.Introduction: The study presents treatment results of 168 patients with non small cell lung cancer in stage IIIB and IV treated since year 2002 to 2006 in Oncological Center in Cracow. Material and methods: Four regimens of chemotherapy: EP (cisplatin, vepesid), MVP (mitomycin C, vinblastin, cisplatin), PN (cisplatin,vinorelbin) and PG (cisplatin, gemcytabin) were used. Results: Average survival time in group treated with MVP regimen was 7,8 months (median 4,3 months), PG 7,1 months (median 7,3 months), EP 10,2 months (median 7,5 months), PN 14,1 months (median 9,8 months). Differences in median survival time were not significant. Average time to progression in group treated with MVP regimen was 3,5 months (median 2,6 months), PG 5,2 months (median 5,8 months): EP 6,6 months (median 5,2 months), PN 6,7 months (median 5,6 months). Improvement in control of symptoms regarding dyspnea, pain and cough was reached in 60%, 38,7% and 60% of patients respectively. There were no significant differences between chemotherapy regimens regarding improvement in symptoms control. Conclusions: Cisplatin + vinorelbin regimen can be recommended as standard method because of the best treatment results

Immunotherapy or targeted therapy as first-line treatment of patients with advanced/metastatic melanoma with the BRAF mutation — a single-center analysis

Introduction. One of the most important achievements of contemporary oncology is the discovery of new therapeutic possibilities: targeted therapy and immunotherapy associated with checkpoint inhibitors. It has not been unequivocally determined so far which therapy should be used as first-line treatment in patients with advanced/metastatic melanoma with the BRAF mutation. Material and methods. 137 patients with advanced/metastatic melanoma with the BRAF mutation were analyzed. They received anti-PD1-1 therapy (IT) or molecularly targeted therapy iBRAF ± iMEK (TT) as first-line treatment in the scope of the national drug program. IT and TT therapies used as first-line treatment were compared. Results. Median OS and PFS in the group were 14.0 and 7.3 months. Unfavorable prognostic factors for OS and PFS were metastases to the central nervous system, increased LDH levels and performance status > 1. Metastatic sites in > 2 locations were only unfavorable prognostic factors for OS. A statistically significant difference was found between TT and IT for OS (p = 0.0011; median for TT was 12.6 months and was not reached for IT). It should be noted that the group treated with TT was characterized by a worse prognostic factors. No differences in PFS were observed (p = 0.292, medians 7.2 and 9.0 months, respectively). Conclusion. In patients with advanced/metastatic melanoma with a BRAF mutation without rapid progression, IT should be considered as first-line therapy.Introduction. One of the most important achievements of contemporary oncology is the discovery of new therapeutic possibilities: targeted therapy and immunotherapy associated with checkpoint inhibitors. It has not been unequivocally determined so far which therapy should be used as first-line treatment in patients with advanced/metastatic melanoma with the BRAF mutation. Material and methods. 137 patients with advanced/metastatic melanoma with the BRAF mutation were analyzed. They received anti-PD1-1 therapy (IT) or molecularly targeted therapy iBRAF ± iMEK (TT) as first-line treatment in the scope of the national drug program. IT and TT therapies used as first-line treatment were compared. Results. Median OS and PFS in the group were 14.0 and 7.3 months. Unfavorable prognostic factors for OS and PFS were metastases to the central nervous system, increased LDH levels and performance status > 1. Metastatic sites in > 2 locations were only unfavorable prognostic factors for OS. A statistically significant difference was found between TT and IT for OS (p = 0.0011; median for TT was 12.6 months and was not reached for IT). It should be noted that the group treated with TT was characterized by a worse prognostic factors. No differences in PFS were observed (p = 0.292, medians 7.2 and 9.0 months, respectively). Conclusion. In patients with advanced/metastatic melanoma with a BRAF mutation without rapid progression, IT should be considered as first-line therapy

Immunoterapia czy terapia celowana w pierwszej linii leczenia chorych na zaawansowane/rozsiane czerniaki z obecnością mutacji BRAF — analiza jednoośrodkowa

Wstęp. Jednym z najważniejszych osiągnięć współczesnej onkologii jest odkrycie nowych możliwości terapeutycznych: terapii celowanej oraz immunoterapii związanej z inhibitorami punktów kontrolnych. Dotychczas nie ustalono jednoznacznie, która terapia powinna być zastosowana jako leczenie pierwszej linii u chorych na zaawansowane/rozsiane czerniaki z obecnością mutacji BRAF.Materiał i metody. Analizą objęto 137 chorych na zaawansowane/przerzutowe czerniaki z obecną mutacją BRAF, otrzymujących w ramach programów lekowych immunoterapię anty-PD-1 (IT) lub terapię ukierunkowaną molekularnie iBRAF ± iMEK (TT) jako leczenie pierwszej linii. Porównano terapie IT i TT stosowane jako leczenie pierwszej linii.Wyniki. Mediany czasu przeżycia całkowitego (OS) i czasu wolnego od progresji choroby (PFS) w całej badanej grupie wyniosły odpowiednio 14,0 i 7,3 miesiąca. Niekorzystnymi czynnikami rokowniczymi w zakresie OS i PFS były przerzuty do ośrodkowego układu nerwowego, podwyższona aktywność dehydrogenazy mleczanowej oraz stan sprawności > 1. Obecność przerzutów w > 2 lokalizacjach była niekorzystnym czynnikiem rokowniczym tylko w zakresie OS. Wykazano znamiennie statystyczną różnicę pomiędzy terapiami TT i IT w zakresie OS (p = 0,0011; mediana dla TT wyniosła 12,6 miesiąca, nie osiągnięto mediany dla IT). Należy jednak zaznaczyć, że grupa leczona TT charakteryzowała się gorszymi czynnikami prognostycznymi. Nie wykazano różnicy w zakresie PFS (p = 0,292; mediana dla TT 7,2 miesiąca, mediana dla IT 9,0 miesięcy).Wnioski. U chorych na zaawansowane/przerzutowe czerniaki z obecną mutacją BRAF bez gwałtownej progresji IT powinna być rozważana jako leczenie pierwszej linii

Biomarkers of trastuzumab-induced cardiac toxicity in HER2- positive breast cancer patient population

SIMPLE SUMMARY: Trastuzumab administered as a (neo)adjuvant therapy in radically treated Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer patients improves overall survival. This study aimed to assess if factors commonly thought to play a role as biomarkers of trastuzumab-induced cardiotoxicity (TIC) are pathognomonic for this injury. Data obtained for 130 HER2-positive breast cancer patients do not support an influence of N-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), or myoglobin on the frequency of TIC. Suggestions for trastuzumab therapy include: close cooperation between cardiologists and oncologists; not using NT-proBNP, CK-MB, or myoglobin as standard TIC predictive markers; organizing prospective studies assessing the role of these parameters as TIC predictive markers in the case of HER2 blockage in conjunction with doublet immunotherapy or other anti-HER2 agents. ABSTRACT: Trastuzumab-induced cardiotoxicity (TIC) can lead to early treatment discontinuation. The aim of this study was to evaluate: N-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), myoglobin, and selected biochemical and clinical factors as predictors of TIC. One hundred and thirty patients with HER2-positive BC receiving adjuvant trastuzumab therapy (TT) were enrolled. Measurement of cardiac markers and biochemical tests as well as echocardiography were performed prior to TT initiation and every three months thereafter. Cardiotoxicity leading to treatment interruption occurred in 24 patients (18.5%). While cardiotoxicity caused early treatment discontinuation in 14 patients (10.8%), the TIC resolved in 10 (7.7%) and TT was resumed. The most common complication was a decrease in left ventricular ejection fraction of more than 10% from baseline or below 50% (7.7%). In patients with TIC, there was no increase in the levels of NT-proBNP, myoglobin, and CK-MB. BMI, hypertension, ischemic heart disease, diabetes, age, cancer stage, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were shown to not have an effect on TIC occurrence. NT-proBNP, myoglobin, and CK-MB are not predictors of TIC. There is an ongoing need to identify biomarkers for TIC

Development of immunity-related adverse events correlates with baseline clinical factors, survival and response to anti-PD-1 treatment in patients with inoperable or metastatic melanoma

Background The relationship between immune related adverse events (irAEs) and efficacy is not definitively proven, and data on the relationship between irAE and treatment efficacy are contradictory. Material and methods Five hundred ninety-three consecutive patients with unresectable or metastatic melanoma treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) between January 2016 and December 2019 were enrolled in the study. Results Statistically significant differences were demonstrated between the group of patients without and with irAE in median OS and PFS (p < .0001 both) and also in OS between the group of patients without irAE and patients with irAE within 3, 6, and 9 months from the start of anti-PD-1 therapy (p = .0121, p = .0014, p < .0001; respectively) and PFS (p = .0369, p = .0052, p = .0001; respectively). A statistically significant relationship was demonstrated between the occurrence of irAE and the location of the primary tumor (skin vs. mucosa vs. unknown; p = .0183), brain metastasis (present vs. absent; p = .0032), other locations (present vs. absent, p = .0032), LDH (normal vs. elevated; p = .0046) and stage according to TNM (p = .0093). Conclusion The occurrence of irAE was associated with longer OS, PFS, and more frequent response to treatment. IrAE occurred statistically significantly more often in patients with mucosa primary tumor, with normal LDH levels, without brain metastases, stages III, M1a, and M1b