Single-agent metronomic versus weekly oral vinorelbine as first-line chemotherapy in patients with HR-positive/HER2-negative advanced breast cancer: The randomized Tempo Breast study.

INTRODUCTION: Single-agent oral vinorelbine is a standard of care for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) that has progressed on endocrine therapy. Metronomic administration may offer a better balance of efficacy and safety than standard regimens, but data from previous trials are scarce. METHODS: In this open-label, multicenter, phase II trial, patients were randomized to oral vinorelbine administered on a metronomic (50 mg three times weekly) or weekly (60 mg/m2 in cycle 1, increasing to 80 mg/m2 if well tolerated) schedule. Treatment was continued until disease progression or intolerance. The primary endpoint was disease control rate (DCR, the proportion of patients with a best overall confirmed response of CR, PR, or stable disease lasting 6 months or more). RESULTS: One-hundred sixty-three patients were randomized and treated. The DCR was 63.4% (95% confidence interval [CI]: 52.0-73.8) with metronomic vinorelbine and 72.8% (95% CI: 61.8-82.1) with weekly vinorelbine. Weekly vinorelbine was also associated with longer progression-free survival (5.6 vs 4.0 months) and overall survival (26.7 vs 22.3 months) than metronomic vinorelbine, but was associated with more adverse events. CONCLUSIONS: In this randomized phase II trial, single-agent metronomic oral vinorelbine was effective and well tolerated as first-line chemotherapy for patients with HR-positive/HER2-negative ABC. Formal comparisons are not done in this phase II study and one can simply observe that confidence intervals of all endpoints overlap. When deciding for a chemotherapy after failure of endocrine therapy and CDK 4/6 inhibitors, oral vinorelbine might be an option to be given with either schedule. CLINICAL TRIAL REGISTRATION NUMBER: EudraCT 2014-003860-19.

Get reliable laboratory findings - how to recognize the deceptive effects of angiotensin-converting enzyme inhibitor therapy in the laboratory diagnostics of sarcoidosis?

OBJECTIVES: Serum angiotensin-converting enzyme (ACE) is the only biomarker routinely used in the laboratory diagnostics of sarcoidosis, and ACE inhibitor (ACEi) drugs are among the most prescribed drugs worldwide. Taking ACEi can mislead medical teams by lowering ACE activity, delaying diagnosis and giving a false impression of disease activity of sarcoidosis. We aimed to develop a simple method to detect the presence of ACEi drugs in samples, to investigate the ACEi medication-caused interference and consequences in a retrospective study. METHODS: ACE activity and the level of ACE inhibition were determined for 1823 patients with suspected sarcoidosis. These values were compared with the therapeutic information at the first and follow-up visits. RESULTS: A total of 302 patients had biochemical evidence of an ACEi drug effect during diagnostic ACE activity testing. In their case, ACE activity was significantly lower (median(IQR): 4.41 U/L(2.93-6.72)) than in patients not taking ACEi (11.32 U/L(8.79-13.92), p<0.01). In 62 sarcoidosis patients, the ACEi reduced ACE activity to the reference range or below. Only in 40 % of the cases was the medication list recorded in the outpatient chart and only in 3 cases was low ACE activity associated with ACEi use. 67 % of the repeated ACE activity measurements were also performed during ACEi therapy. CONCLUSIONS: Our study revealed that the use of ACEi is common in patients with suspected sarcoidosis. The ACE activity lowering effect of ACEi drugs may escape the attention of medical teams which can lead to diagnostic errors and unnecessary tests. Nevertheless, these pitfalls can be avoided by using a method suggested by our team.

[Fertility preservation in female cancer patients.] / Daganatos nobetegek termékenységének megorzése.

In Hungary, an average of 2066 women under the age of 40 are diagnosed with cancer each year according to data from the National Cancer Registry. Approximately two-thirds of these patients require gonadotoxic treatment for their disease, which could potentially reduce their chances of future conception and childbirth. Currently, there are no professional guidelines on fertility preservation in Hungary, however, it is important to inform patients about their options. In our previous paper, we presented the gonadotoxic effects of oncotherapies and the currently available fertility preservation techniques. This second paper provides current treatment methods and recommends fertility preservation techniques in different cancer types. The success of an oncofertility program relies heavily on the effective communication and collaboration between oncologists and reproductive specialists involved in fertility preservation. This paper may be the first step in elaborating a guideline towards improving access to oncofertility services and ultimately improving the quality of life for young cancer survivors in Hungary. Orv Hetil. 2023; 164(29): 1134-1145.

Hazai tapasztalatok metasztatikus kolorektális karcinóma bevacizumabbal kiegészített indukciós kemoterápiás kezelésével (AVACONT vizsgálat).

The primary aim of AVACONT was to collect data in the course of routine oncological care from patients with metastatic colorectal cancer (mCRC) treated with bevacizumab supplemented fluoropyrimidine-based chemotherapy doublet in an open, multicentre, observational study in Hungary. Primary endpoint of the study was to determine progression-free survival (PFS). The Full Analysis Set (FAS) comprised 280 patients. Median PFS calculated from enrolment was 270 days in the FAS population. The metastatic involvement of the liver or more than one organ significantly decreased (250 and 245 days), while a clinical response achieved significantly increased (partial response: 404, complete response: 623 days) the mPFS calculated from enrolment. PFS calculated from the start of the first-line treatment was significantly decreased by the presence of mutant RAS gene (481 vs. 395 days). The results confirm the efficacy, known prognostic factors and safety profile of bevacizumab in combination with chemotherapy dosed during standard oncology care in Hungarian centres.

Correlation between Tissue Cellularity and Metabolism Represented by Diffusion-Weighted Imaging (DWI) and 18F-FDG PET/MRI in Head and Neck Cancer (HNC).

BACKGROUND: This study aimed to assess the association of 18F-Fluorodeoxyglucose positron-emission-tomography (18F-FDG/PET) and DWI imaging parameters from a primary tumor and their correlations with clinicopathological factors. METHODS: We retrospectively analyzed primary tumors in 71 patients with proven HNC. Primary tumor radiological parameters: DWI and FDG, as well as pathological characteristics were analyzed. Spearman correlation coefficient was used to assess the correlation between DWI and FDG parameters, ANOVA or Kruskal-Wallis, independent sample t-test, Mann-Whitney test, and multiple regression were performed on the clinicopathological features that may affect the 18F- FDG and apparent-diffusion coefficient (ADC) of the tumor. RESULTS: No significant correlations were observed between DWI and any of the 18F-FDG parameters (p > 0.05). SUVmax correlated with N-stages (p = 0.023), TLG and MTV correlated with T-stages (p = 0.006 and p = 0.001), and ADC correlated with tumor grades (p = 0.05). SUVmax was able to differentiate between N+ and N- groups (p = 0.004). CONCLUSIONS: Our results revealed a non-significant correlation between the FDG-PET and ADC-MR parameters. FDG-PET-based glucose metabolic and DWI-MR-derived cellularity data may represent different biological aspects of HNC.

Pre-treatment PET/MRI based FDG and DWI imaging parameters for predicting HPV status and tumor response to chemoradiotherapy in primary oropharyngeal squamous cell carcinoma (OPSCC).

OBJECTIVES: To determine the feasibility of pre-treatment primary tumor FDG-PET and DWI-MR imaging parameters in predicting HPV status and the second aim was to assess the feasibility of those imaging parameters to predict response to therapy. MATERIAL AND METHODS: We retrospectively analyzed primary tumors in 33 patients with proven OPSCC. PET/MRI was performed before and 6 months after chemo-radiotherapy for assessing treatment response. PET Standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and apparent diffusion coefficient (ADC) from pre-treatment measurements were assessed and compared to the clinicopathological characteristics (T stages, N stages, tumor grades, HPV and post-treatment follow up). HPV was correlated to the clinicopathological characteristics. RESULTS: ADCmean was significantly lower in patients with HPV+ve than HPV-ev, (P = 0.001), cut off value of (800 ± 0.44*10-3mm2/s) with 76.9% sensitivity, and 72.2% specificity is able to differentiate between the two groups. No significant differences were found between FDG parameters (SUVmax, TLG, and MTV), and HPV status, (P = 0.873, P = 0.958, and P = 0.817), respectively. Comparison between CR and NCR groups; ADCmean, TLG, and MTV were predictive parameters of treatment response, (P = 0.017, P = 0.013, and P = 0.014), respectively. HPV+ve group shows a higher probability of lymph nodes involvement, (P = 0.006) CONCLUSION: Our study found that pretreatment ADC of the primary tumor can predict HPV status and treatment response. On the other hand, metabolic PET parameters (TLG, and MTV) were able to predict primary tumor response to therapy.

Diffusion-Weighted Imaging (DWI) derived from PET/MRI for lymph node assessment in patients with Head and Neck Squamous Cell Carcinoma (HNSCC).

BACKGROUND: To determine the usefulness of Diffusion Weighted Imaging (DWI) derived from PET/MRI in discriminating normal from metastatic lymph nodes and the correlation between the metastatic lymph nodes with the grade and the localization of the primary tumor. METHODS: Retrospective study of 90 lymph nodes from 90 subjects; 65 patients who had proven histopathological metastatic lymph nodes from (HNSCC) who had undergone 18F- PET/MRI for clinical staging and assessment and twenty-five lymph nodes were chosen from 25 healthy subjects. Apparent Diffusion Coefficient (ADC) map was generated from DWI with b values (0 and 800 s/mm2). ADC values of the metastatic lymph nodes were calculated and compared to the normal lymph nodes ADC values, ROC was used to determine the best cut-off values to differentiate between the two group. Metastatic lymph nodes ADC mean values were compared to primary tumor grade and localization. RESULTS: ADCmean value of the metastatic lymph nodes in the overall sample (0.899 ± 0.98*10- 3 mm2/sec) was significantly lower than the normal lymph nodes' ADCmean value (1.267 ± 0.88*10- 3 mm2/sec); (P = 0.001). The area under the curve (AUC) was 98.3%, sensitivity and specificity were 92.3 and 98.6%, respectively, when using a threshold value of (1.138 ± 0.75*10- 3 mm2/sec) to differentiate between both groups. Significant difference was found between metastatic lymph nodes (short-axis diameter < 10 mm), ADCmean (0.898 ± 0.72*10- 3 mm2/sec), and the benign lymph nodes ADCmean, (P = 0.001). No significant difference was found between ADCmean of the metastatic lymph nodes < 10 mm and the metastatic lymph nodes > 10 mm, ADCmean (0.899 ± 0.89*10- 3 mm2/sec), (P = 0.967). No significant differences were found between metastatic lymph nodes ADCmean values and different primary tumor grades or different primary tumor localization, (P > 0.05). CONCLUSION: DWI-ADC is an effective and efficient imaging technique in differentiating between normal and malignant lymph nodes, and might be helpful to discriminate sub-centimeters lymph nodes. TRIAL REGISTRATION: The trial is registered in clinical trials under ID: NCT04360993 , registration date: 17/04/2020.

Overall survival results from the randomized phase 2 study of palbociclib in combination with letrozole versus letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (PALOMA-1, TRIO-18).

PURPOSE: Palbociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, approved in combination with endocrine therapy for the treatment of women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC). In the phase 2, open-label, PALOMA-1 trial, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) versus letrozole alone (hazard ratio, 0.488; 95% CI 0.319‒0.748; P = 0.0004; median PFS, 20.2 vs 10.2 months, respectively) in postmenopausal women with estrogen receptor-positive (ER+)/HER2- ABC. Here, we present the final overall survival (OS) and updated safety results. METHODS: Postmenopausal women with ER+/HER2- ABC were randomized 1:1 to receive either palbociclib (125 mg/day, 3/1 schedule) plus letrozole (2.5 mg/day, continuous) or letrozole alone (2.5 mg/day, continuous). The primary endpoint was investigator-assessed PFS; secondary endpoints included OS and safety. RESULTS: A total of 165 patients were randomized. At the data cutoff date of December 30, 2016 (median duration of follow-up, 64.7 months), the stratified hazard ratio for OS was 0.897 (95% CI 0.623-1.294; P = 0.281); median OS in the palbociclib plus letrozole and letrozole alone arms was 37.5 and 34.5 months, respectively. The median time from randomization to first subsequent chemotherapy use was longer with palbociclib plus letrozole than letrozole alone (26.7 and 17.7 months, respectively). The most frequently reported adverse event in the palbociclib plus letrozole arm was neutropenia (any grade, 75%; grade 3 or 4, 59%). CONCLUSIONS: Palbociclib plus letrozole treatment led to a numerical but not statistically significant improvement in median OS. Pfizer Inc (NCT00721409).

[Paclitaxel containing chemotherapeutic regimens in first line and reintroduced palliative treatment of metastatic cervical cancer]. / Paklitaxeltartalmú kemoterápiás kombináció metasztatikus cervixtumor elso vonali és reindukciós palliatív kezelésében.

INTRODUCTION: The paclitaxel-carboplatin doublet is an alternative choice in the first line treatment of metastatic or recurrent cervical cancer according to international guidelines. METHOD: The history of seven patients treated with paclitaxel-platinum in the last three years in the Petz Aladár Hospital is reported. A case report, supporting the efficacy of the combination in emergency and in reintroduced settings is presented as well. RESULTS: The average progression-free survival was 10 months. All patients were alive at the time of the submission of the article. CONCLUSION: The results confirm the efficacy of the paclitaxel-carboplatin AUC 5 and the paclitaxel-cisplatin combinations in the treatment of metastatic cervical cancer. Orv Hetil. 2018; 159(24): 974-977.

[Stereotactic body radiotherapy of liver metastasis: early experience]. / Májáttétes betegek sztereotaxiás ablatív sugárkezelésével (SABRT) elért elsõ eredményeink.

Recently the prevalence of oligometastatic patients is increasing. A common site of distant spread is the liver. The standard of care is curative surgical resection, however, the resecability rate is only 10-20%. Alternatively, radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) may be used. Stereotactic ablative body radiotherapy (SABRT) makes it possible to deliver curative radiation dose without radiation injury to the healthy liver tissue. We delivered SABRT to three patients with inoperable hepatic metastases. The primary tumors were rectal (2) and lung (1). The dose was 3x20 Gy every other day. We observed one grade 1 side effect. All the metastases showed complete remission and no local recurrence or late side effect occurred during the one year of follow-up. One patient is tumor-free, one has stable disease, in one patient two new hepatic metastases appeared and receives chemo-biological therapy. SABRT of liver metastases is safe and highly effective. It can be expected that in the near future it will become one of the standard treatments of hepatic tumors.

Predictive Value of Early Skin Rash in Cetuximab-Based Therapy of Advanced Biliary Tract Cancer.

Randomized trials in advanced biliary tract cancer (BTC) did not show benefit of cetuximab addition over chemotherapy. This is probably due to the lack of predictive biomarkers. The aim of this study was to explore possible predictive factors. Between 2009 and 2014, 57 patients were treated in 3-week cycles with cetuximab (250 mg/m2/week, loading dose: 400 mg/m2), gemcitabine (1000 mg/m2 on day 1 and 8), and capecitabine (1300 mg/m2/day on days 1-14). The objective response rate (ORR), progression-free (PFS) and overall survival (OS) and the adverse events (AEs) were evaluated. An exploratory analysis was performed to find possible predictive factors on clinicopathological characteristics, routine laboratory parameters and early AEs, which occurred within 2 months from the beginning of treatment. The ORR was 21%. The median PFS and OS were 34 (95% CI: 24-40) and 54 (43-67) weeks, respectively. The most frequent AEs were skin toxicities. In univariate analysis performance status, previous stent implantation, thrombocyte count at the start of therapy, early neutropenia and skin rash statistically significantly influenced the ORR, PFS and/or OS. In multivariate Cox regression analysis only normal thrombocyte count at treatment start and early acneiform rash were independent markers of longer survival. In patients showing early skin rash compared to the others the median PFS was 39 vs. 13 weeks and the median OS was 67 vs. 26 weeks, respectively. It is suggested that early skin rash can be used as a biomarker to select patients who would benefit from the treatment with cetuximab plus chemotherapy.

[Does the sidedness determine the first line treatment of irresectable metastatic colorectal cancer?] / Meghatározza-e az oldaliság az irreszekábilis metasztatikus colorectalis carcinoma elso vonalbeli kezelését?

INTRODUCTION AND AIM: Median life expectancy of non-resectable metastatic colorectal cancer may surpass three years. However, several points of the treatment strategy are subject of ongoing debate. Optimal sequence of targeted agents is not elucidated either. Based on retrospective analyses of six clinical studies and a metaanalysis, the superiority of anti-EGFR agents such as cetuximab and panitumumab over anti-VEGF bevacizumab has been proposed in the treatment of left sided tumours. METHOD: The results of the six major clinical trials were analysed. Insufficiencies of the meta-analysis are pointed: the lack of homogeneity among control groups, the omission of later lines of therapy, the inconsistency between progression free and overall survival benefit and the high proportion of excluded patients. RESULTS: The trials confirm the worse prognosis of right sided versus left sided colorectal cancers. CONCLUSION: To date the data are not strong enough to support the preference of any of the available targeted agents at the first line setting in the treatment of left sided metastatic RAS and BRAF wild type colorectal cancers. Several trials suggest that anti-EGFR treatment has no additional benefit as compared to chemotherapy alone in the treatment of right-sided tumours. Orv. Hetil., 2017, 158(9), 340-344.

A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pegfilgrastim in Patients Receiving First-Line FOLFOX/Bevacizumab or FOLFIRI/Bevacizumab for Locally Advanced or Metastatic Colorectal Cancer: Final Results of the Pegfilgrastim and Anti-VEGF Evaluation Study (PAVES).

BACKGROUND: Pegfilgrastim's role in reducing the risk of febrile neutropenia (FN) in patients with colorectal cancer (CRC) receiving chemotherapy plus bevacizumab was not previously evaluated in a prospective study. The present phase III, double-blind trial evaluated the efficacy of pegfilgrastim versus placebo in reducing the incidence of grade 3/4 FN in patients with advanced CRC receiving bevacizumab combined with first-line chemotherapy (FOLFOX [leucovorin, 5-fluorouracil, oxaliplatin] or FOLFIRI [leucovorin, 5-fluorouracil, irinotecan]). PATIENTS AND METHODS: Patients aged ≥ 18 years with locally advanced or metastatic CRC were randomized 1:1 to placebo or 6 mg of pegfilgrastim ∼24 hours after receiving chemotherapy plus bevacizumab every 14 days. The study treatment period included 4 cycles, but patients could continue treatment for ≤ 60 months. The primary endpoint was incidence of grade 3/4 FN in the first 4 cycles. The secondary endpoints included the objective response rate (ORR), overall survival, and progression-free survival, analyzed at the end of the long-term follow-up period. RESULTS: A total of 845 patients were randomized from November 2009 to January 2012 (422, pegfilgrastim; 423, placebo). Pegfilgrastim significantly reduced the incidence of grade 3/4 FN in the first 4 treatment cycles (pegfilgrastim, 2.4%; 95% confidence interval [CI], 1.1%-4.3%; placebo, 5.7%; 95% CI, 3.7%-8.3%; odds ratio [OR], 0.41; P = .014). No significant differences were observed between the 2 arms in ORR (OR, 1.15; P = .330), overall survival (hazard ratio, 0.94; P = .440), and progression-free survival (hazard ratio, 0.93; P = .300). CONCLUSION: Pegfilgrastim reduced the FN incidence in patients with advanced CRC receiving chemotherapy and bevacizumab. Administration of pegfilgrastim was tolerable and did not negatively affect the tumor response or survival in this patient population.

[Effective systemic palliative chemotherapy for intracranial metastases of breast cancer]. / Emlotumor intracranialis metasztázisainak eredményes szisztémás palliatív kemoterápiája.

The authors present the history of two patients. The first patient, a 69-year-old woman was diagnosed with locally invasive triple negative breast cancer with pulmonary and cerebral metastases. Complete radiological remission of the clinically asymptomatic cerebral metastases was detected under systemic chemotherapy with carboplatin-docetaxel (75 mg/m2). Later, the patient received whole brain radiotherapy and a second line of chemotherapy. The overall survival was 20 months from the diagnosis of cerebral metastases with conservation of partial autonomy. The second patient, a 57-year-old woman was diagnosed as having hormone sensitive lobular breast cancer with leptomeningeal, lymphonodular and multiple osseal metastases. Before the appearance of the lymphonodular metastasis the patient received intrathecal methotrexate chemotherapy for the leptomeningeal carcinomatosis. Her neurological symptoms completely disappeared. At the onset of the lymphonodular metastasis systemic chemotherapy with ifosfamide (1000 mg/m2, D1-3) - etoposide (100 mg/m2, D1-3) was started allowing complete clinical remission of the lymphadenomegaly and stability of the asymptomatic neurological status. The overall survival was 13 months from the diagnosis of leptomeningeal carcinomatosis with conservation of autonomy. The two cases support potential efficacy of systemic chemotherapy for intracranial metastases of breast cancer. Orv. Hetil., 2016, 157(45), 1809-1813.

Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18.

BACKGROUND: Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6. In the randomized, open-label, phase II PALOMA-1/TRIO-18 trial, palbociclib in combination with letrozole improved progression-free survival (PFS) compared with letrozole alone as first-line treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer (20.2 months versus 10.2 months; hazard ratio (HR) = 0.488, 95 % confidence interval (CI) 0.319-0.748; one-sided p = 0.0004). Grade 3-4 neutropenia was the most common adverse event (AE) in the palbociclib + letrozole arm. We now present efficacy and safety analyses based on several specific patient and tumor characteristics, and present in detail the clinical patterns of neutropenia observed in the palbociclib + letrozole arm of the overall safety population. METHODS: Postmenopausal women (n = 165) with ER+, HER2-negative, advanced breast cancer who had not received any systemic treatment for their advanced disease were randomized 1:1 to receive either palbociclib in combination with letrozole or letrozole alone. Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, or death. The primary endpoint was PFS. We now analyze the difference in PFS for the treatment populations by subgroups, including age, histological type, history of prior neoadjuvant/adjuvant systemic treatment, and sites of distant metastasis, using the Kaplan-Meier method. HR and 95 % CI are derived from a Cox proportional hazards regression model. RESULTS: A clinically meaningful improvement in median PFS and clinical benefit response (CBR) rate was seen with palbociclib + letrozole in every subgroup evaluated. Grade 3-4 neutropenia was the most common AE with palbociclib + letrozole in all subgroups. Analysis of the frequency of neutropenia by grade during the first six cycles of treatment showed that there was a downward trend in Grade 3-4 neutropenia over time. Among those who experienced Grade 3-4 neutropenia, 71.7 % had no overlapping infections of any grade and none had overlapping Grade 3-4 infections. CONCLUSION: The magnitude of clinical benefit seen with the addition of palbociclib to letrozole in improving both median PFS and CBR rate is consistent in nearly all subgroups analyzed, and consistent with that seen in the overall study population. The safety profile of the combination treatment in all subgroups was also comparable to that in the overall safety population of the study.

[Effective palliative chemotherapy in a patient with collecting duct carcinoma of a unilateral kidney associated with anuria. Case report]. / Féloldali vese gyujtocsatornás daganatának eredményes palliatív kemoterápiás kezelése anuria mellett.

The case of a 54-year-old woman is presented. She underwent right sided unilateral nephrectomy for metastatic bilateral renal tumour of the Bellini collecting ducts. Progression of the contralateral tumour resulted in acute complete anuric renal failure. Haemodialysis was started along with palliative gemcitabine (1000 mg/m(2))-cisplatine (70 mg/m(2)) chemotherapy. In parallel, renal function was improving and dialysis could be stopped at the end of the chemotherapy line comprising 6 cycles. Half a year later the patient was lost of uncontrolled local and pulmonary progression. The potentially nephrotoxic cisplatine chemotherapy associated to complex supportive treatment improved the renal function by controlling diffusely infiltrative tumour growth and allowed a survival benefit over one year with active household keeping capacity.

[New option in the management of cancer pain in Hungary: short acting oral opioid therapy]. / Új lehetoség a daganatos fájdalom csillapításában Magyarországon: rövid hatású major analgetikumok.

Short acting oral morphine has recently been registered again in Hungary. Short acting oral morphine has two essential indications: dose titration at initiation of major analgesic therapy and treatment of breakthrough pain appearing beside round the clock major analgesic therapy. The clinical management of short acting oral morphine is summarised in this article.

The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.

BACKGROUND: Palbociclib (PD-0332991) is an oral, small-molecule inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 with preclinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens. We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer. METHODS: In this open-label, randomised phase 2 study, postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate. Patients were enrolled in two separate cohorts that accrued sequentially: in cohort 1, patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone, whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both. In both cohorts, patients were randomly assigned 1:1 via an interactive web-based randomisation system, stratified by disease site and disease-free interval, to receive continuous oral letrozole 2.5 mg daily or continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 (instead of cohort 2 alone). The study is ongoing but closed to accrual; these are the results of the final analysis of progression-free survival. The study is registered with the ClinicalTrials.gov, number NCT00721409. FINDINGS: Between Dec 22, 2009, and May 12, 2012, we randomly assigned 165 patients, 84 to palbociclib plus letrozole and 81 to letrozole alone. At the time of the final analysis for progression-free survival (median follow-up 29.6 months [95% CI 27.9-36.0] for the palbociclib plus letrozole group and 27.9 months [25.5-31.1] for the letrozole group), 41 progression-free survival events had occurred in the palbociclib plus letrozole group and 59 in the letrozole group. Median progression-free survival was 10.2 months (95% CI 5.7-12.6) for the letrozole group and 20.2 months (13.8-27.5) for the palbociclib plus letrozole group (HR 0.488, 95% CI 0.319-0.748; one-sided p=0.0004). In cohort 1 (n=66), median progression-free survival was 5.7 months (2.6-10.5) for the letrozole group and 26.1 months (11.2-not estimable) for the palbociclib plus letrozole group (HR 0.299, 0.156-0.572; one-sided p<0.0001); in cohort 2 (n=99), median progression-free survival was 11.1 months (7.1-16.4) for the letrozole group and 18.1 months (13.1-27.5) for the palbociclib plus letrozole group (HR 0.508, 0.303-0.853; one-sided p=0.0046). Grade 3-4 neutropenia was reported in 45 (54%) of 83 patients in the palbociclib plus letrozole group versus one (1%) of 77 patients in the letrozole group, leucopenia in 16 (19%) versus none, and fatigue in four (4%) versus one (1%). Serious adverse events that occurred in more than one patient in the palbociclib plus letrozole group were pulmonary embolism (three [4%] patients), back pain (two [2%]), and diarrhoea (two [2%]). No cases of febrile neutropenia or neutropenia-related infections were reported during the study. 11 (13%) patients in the palbociclib plus letrozole group and two (2%) in the letrozole group discontinued the study because of adverse events. INTERPRETATION: The addition of palbociclib to letrozole in this phase 2 study significantly improved progression-free survival in women with advanced oestrogen receptor-positive and HER2-negative breast cancer. A phase 3 trial is currently underway. FUNDING: Pfizer.

Health-related quality of life with adjuvant docetaxel- and trastuzumab-based regimens in patients with node-positive and high-risk node-negative, HER2-positive early breast cancer: results from the BCIRG 006 Study.

BACKGROUND: This study aims to describe and compare health-related quality of life (HRQL) in patients with node-positive and high-risk node-negative HER2-positive early breast cancer receiving adjuvant docetaxel and trastuzumab-based or docetaxel-based regimens alone. METHODS: Eligible patients (n = 3,222) were randomly assigned to either four cycles of adjuvant doxorubicin and cyclophosphamide followed by four cycles of docetaxel (AC→T) or one of two trastuzumab-containing regimens: adjuvant doxorubicin and cyclophosphamide followed by docetaxel plus trastuzumab administered for 1 year (AC→TH) or six cycles of docetaxel plus carboplatin combined with trastuzumab administered for 1 year (TCH). The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and BR-23 were administered at baseline, the start of cycle 4 (mid), and the end of chemotherapy (EOC), as well as at 6, 12, and 24 months after chemotherapy. RESULTS: Compliance rates for the EORTC questionnaires were acceptable at 72%-93% of eligible patients out to the 12-month assessment. Systemic side effect (SE) change scores were significantly improved for TCH-treated patients compared with AC→TH and AC→T at EOC, suggesting improved tolerability. Physical functioning (PF) was only slightly worse at midpoint for those receiving TCH, compared with patients who were just starting on taxane in an AC→TH regimen, but was otherwise similar between arms. All treatment arms recovered from the deterioration in SE, PF, and Global Health Scale scores by 1 year and median future perspective change scores continued to improve throughout treatment and follow-up. CONCLUSION: HRQL outcomes for adjuvant docetaxel and trastuzumab-based regimens are favorable and support TCH as a more tolerable treatment option.

Abagovomab as maintenance therapy in patients with epithelial ovarian cancer: a phase III trial of the AGO OVAR, COGI, GINECO, and GEICO--the MIMOSA study.

PURPOSE: To determine whether abagovomab maintenance therapy prolongs recurrence-free (RFS) and overall survival (OS) in patients with ovarian cancer in first clinical remission. PATIENTS AND METHODS: Patients with International Federation of Gynecology and Obstetrics stage III to IV ovarian cancer in complete clinical remission after primary surgery and platinum- and taxane-based chemotherapy were randomly assigned at a ratio of 2:1 in a phase III, double-blind, placebo-controlled, multicenter study. Abagovomab 2 mg or placebo was administered as 1-mL suspension once every 2 weeks for 6 weeks (induction phase) and then once every 4 weeks (maintenance phase) until recurrence or up to 21 months after random assignment of the last patient. The primary end point was RFS; secondary end points were OS and immunologic response. RESULTS: Characteristics of the 888 patients included: mean age, 56.3 years; Eastern Cooperative Oncology Group performance status, ≤ 1 in > 99% of patients; serous papillary subtype, 81.5%; stage III, 85.9%; and cancer antigen 125 ≤ 35 U/mL after third cycle, 80.9%. Mean exposure to study treatment (± standard deviation) was 449.7 ± 333.08 days. Hazard ratio (HR) of RFS for the treatment group using tumor size categorization (≤ 1 cm, > 1 cm) was 1.099 (95% CI, 0.919 to 1.315; P = .301). HR of OS using tumor size categorization (≤ 1 cm, > 1 cm) was 1.150 (95% CI, 0.872 to 1.518; P = .322). The most frequently reported type of adverse event was an injection site reaction in 445 patients (50.2%), followed by injection site erythema and fatigue in 227 (25.6%) and 212 patients (23.9%), respectively. By the final visit, median anti-anti-idiotypic antibody level was 493,000.0 ng/mL, indicating a robust response. CONCLUSION: Abagovomab administered as repeated monthly injections is safe and induces a measurable immune response. Administration as maintenance therapy for patients with ovarian cancer in first remission does not prolong RFS or OS.