Time filter

Source Type

PubMed | Queen's University of Belfast, Chelyabinsk Regional Clinical Oncology Dispensary, University of Michigan, Taipei Veterans General Hospital and 6 more.
Type: Journal Article | Journal: Molecular cancer therapeutics | Year: 2016

An exploratory phase II biomarker-embedded trial (LPT109747; NCT00526669) designed to determine the association of lapatinib-induced fluoropyrimidine gene changes with efficacy of lapatinib plus capecitabine as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma independent of tumor HER2 status. Tumor biopsies obtained before and after 7-day lapatinib (1,250 mg) to analyze changes in gene expression, followed by a 14-day course of capecitabine (1,000 mg/m(2) twice daily, 14/21 days) plus lapatinib 1,250 mg daily. Blood samples were acquired for pharmacokinetic analysis. Primary clinical objectives were response rate (RR) and 5-month progression-free survival (PFS). Secondary objectives were overall survival (OS), PFS, time to response, duration of response, toxicity, and identification of associations between lapatinib pharmacokinetics and biomarker endpoints. Primary biomarker objectives were modulation of 5-FU-pathway genes by lapatinib, effects of germline SNPs on treatment outcome, and trough steady-state plasma lapatinib concentrations. Sixty-eight patients were enrolled; (75% gastric cancer, 25% gastroesophageal junction). Twelve patients (17.9%) had confirmed partial response, 31 (46.3%) had stable disease, and 16 (23.9%) had progressive disease. Median PFS and OS were 3.3 and 6.3 months, respectively. Frequent adverse events included diarrhea (45%), decreased appetite (39%), nausea (36%), and fatigue (36%). Lapatinib induced no changes in gene expression from baseline and no significant associations were found for SNPs analyzed. Elevated baseline HER3 mRNA expression was associated with a higher RR (33% vs. 0%; P = 0.008). Lapatinib plus capecitabine was well tolerated, demonstrating modest antitumor activity in patients with advanced gastric cancer. The association of elevated HER3 and RR warrants further investigation as an important player for HER-targeted regimens in combination with capecitabine. Mol Cancer Ther; 15(9); 2251-8. 2016 AACR.


PubMed | Public Clinical Treatment and Prophylaxis Institution, Republic Oncology Dispensary, Royal Marsden Hospital NHS Trust, Chelyabinsk Regional Clinical Oncology Dispensary and 10 more.
Type: Journal Article | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2016

To prospectively determine the efficacy of naptumomab estafenatox (Nap) + IFN versus IFN in metastatic renal cell carcinoma (RCC).In a randomized, open-label, multicenter, phase II/III study, 513 patients with RCC received Nap (15 g/kg i. v. in three cycles of four once-daily injections) + IFN (9 MU s.c. three times weekly), or the same regimen of IFN monotherapy. The primary endpoint was overall survival (OS).This phase II/III study did not meet its primary endpoint. Median OS/PFS for Nap + IFN patients was 17.1/5.8 months versus 17.5/5.8 months for the patients receiving IFN alone (P = 0.56; HR, 1.08/P = 0.41; HR, 0.92). Post hoc exploratory subgroup and trend analysis revealed that the baseline plasma concentrations of anti-SEA/E-120 (anti-Nap antibodies) for drug exposure and IL6 for immune status could be used as predictive biomarkers. A subgroup of patients (SG; n = 130) having concentrations below median of anti-SEA/E-120 and IL6 benefitted greatly from the addition of Nap. In SG, median OS/PFS for the patients treated with Nap + IFN was 63.3/13.7 months versus 31.1/5.8 months for the patients receiving IFN alone (P = 0.02; HR, 0.59/P = 0.02; HR, 0.62). Addition of Nap to IFN showed predicted and transient immune related AEs and the treatment had an acceptable safety profile.The study did not meet its primary endpoint. Nap + IFN has an acceptable safety profile, and results from post hoc subgroup analyses showed that the treatment might improve OS/PFS in a baseline biomarker-defined RCC patient subgroup. The results warrant further studies with Nap in this subgroup. Clin Cancer Res; 22(13); 3172-81. 2016 AACR.


Gladkov O.,Chelyabinsk Regional Clinical Oncology Dispensary | Moiseyenko V.,Nn Petrov Research Institute Of Oncology | Bondarenko I.N.,Dnipropetrovsk State Medical Academy | Shparyk Y.,Lviv Cancer Center | And 3 more authors.
Oncologist | Year: 2015

Objectives. This study aimed to evaluate the efficacy and safety of once-per-cycle balugrastim versus pegfilgrastim for neutrophil support in breast cancer patients receiving myelosuppressive chemotherapy. Methods. Breast cancer patients (n=256) were randomized to 40 or 50 mg of subcutaneous balugrastim or 6 mg of pegfilgrastim ≈24 hours after chemotherapy (60 mg/m2 doxorubicin and 75 mg/m2 docetaxel, every 21 days for up to 4 cycles).The primary efficacy parameter was the duration of severe neutropenia (DSN) in cycle 1. Secondary parameters included DSN (cycles 2–4), absolute neutrophil count (ANC) nadir, febrile neutropenia rates, and time to ANC recovery (cycles 1–4). Safety, pharmacokinetics, and immunogenicity were assessed. Results. Mean cycle 1 DSN was 1.0 day with 40mg of balugrastim, 1.3 with 50mg of balugrastim, and 1.2 with pegfilgrastim (upperlimit of 95% confidence intervals for between-group DSN differences was,1.0 day for both balugrastim doses versus pegfilgrastim). Between-group efficacy parameters were comparable except for time to ANC recovery in cycle 1 (40 mg of balugrastim, 2.0 days; 50mg of balugrastim, 2.1; pegfilgrastim, 2.6).Median terminal elimination half-life was ≈37 hours for 40 mg of balugrastim, ≈36 for 50mgof balugrastim, and ≈45 for pegfilgrastim.Antibody response to balugrastimwas low and transient, with no neutralizing effect. Conclusion. Once-per-cycle balugrastim is not inferior to pegfilgrastim in reducing cycle 1 DSN in breast cancer patients receiving chemotherapy; both drugs have comparable safety profiles. © AlphaMed Press 2016.


PubMed | Lviv Cancer Center, Chelyabinsk Regional Clinical Oncology Dispensary, Teva Pharmaceuticals Inc., Teva Biopharmaceuticals and 2 more.
Type: Clinical Trial, Phase III | Journal: The oncologist | Year: 2016

This study aimed to evaluate the efficacy and safety of once-per-cycle balugrastim versus pegfilgrastim for neutrophil support in breast cancer patients receiving myelosuppressive chemotherapy.Breast cancer patients (n = 256) were randomized to 40 or 50 mg of subcutaneous balugrastim or 6 mg of pegfilgrastim 24 hours after chemotherapy (60 mg/m(2) doxorubicin and 75 mg/m(2) docetaxel, every 21 days for up to 4 cycles). The primary efficacy parameter was the duration of severe neutropenia (DSN) in cycle 1. Secondary parameters included DSN (cycles 2-4), absolute neutrophil count (ANC) nadir, febrile neutropenia rates, and time to ANC recovery (cycles 1-4). Safety, pharmacokinetics, and immunogenicity were assessed.Mean cycle 1 DSN was 1.0 day with 40 mg of balugrastim, 1.3 with 50 mg of balugrastim, and 1.2 with pegfilgrastim (upper limit of 95% confidence intervals for between-group DSN differences was <1.0 day for both balugrastim doses versus pegfilgrastim). Between-group efficacy parameters were comparable except for time to ANC recovery in cycle 1 (40 mg of balugrastim, 2.0 days; 50 mg of balugrastim, 2.1; pegfilgrastim, 2.6). Median terminal elimination half-life was 37 hours for 40 mg of balugrastim, 36 for 50 mg of balugrastim, and 45 for pegfilgrastim. Antibody response to balugrastim was low and transient, with no neutralizing effect.Once-per-cycle balugrastim is not inferior to pegfilgrastim in reducing cycle 1 DSN in breast cancer patients receiving chemotherapy; both drugs have comparable safety profiles.This paper provides efficacy and safety data for a new, once-per-cycle granulocyte colony-stimulating factor, balugrastim, for the prevention of chemotherapy-induced neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy. In this phase III trial, balugrastim was shown to be not inferior to pegfilgrastim in the duration of severe neutropenia in cycle 1 of doxorubicin/docetaxel chemotherapy, and the safety profiles of the two agents were similar. Once-per-cycle balugrastim is a safe and effective alternative to pegfilgrastim for hematopoietic support in patients with breast cancer receiving myelosuppressive chemotherapy associated with a greater than 20% risk of developing febrile neutropenia.


PubMed | Centrul de Oncologie Medicala, Merckle GmbH, Dnipropetrovsk State Medical Academy and Chelyabinsk Regional Clinical Oncology Dispensary
Type: Journal Article | Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer | Year: 2016

Lipegfilgrastim, a glycoPEGylated recombinant granulocyte colony-stimulating factor (G-CSF), reduces neutropenia duration and febrile neutropenia (FN) incidence in patients with cancer receiving myelosuppressive chemotherapy. A phase 3 trial of lipegfilgrastim was conducted in patients with advanced non-small cell lung cancer (NSCLC) receiving cisplatin/etoposide (which produces mild-to-moderate myelosuppression). Because patients aged >65years are at higher risk for FN versus younger patients, this post hoc analysis compared outcomes in elderly (>65years) versus younger participants in this trial.Patients were randomized 2:1 to receive a once-per-cycle single subcutaneous injection of lipegfilgrastim 6mg or placebo, with up to 4 cycles of every-3-week cisplatin (day 1) and etoposide (days 1-3). The primary end point was FN incidence during cycle 1. Outcomes were compared across treatment groups and by age groups (65 and >65years).For patients aged 65years, FN incidence during cycle 1 was similar in the lipegfilgrastim and placebo groups (3.0 vs 3.2%, respectively), whereas for elderly patients, there was a reduction in FN incidence with lipegfilgrastim (0 vs 13.3%, respectively). In both age subgroups, lipegfilgrastim showed a propensity to reduce the incidence and duration of severe neutropenia, time to absolute neutrophil count (ANC) recovery, and depth of ANC nadir. Adverse events were generally similar between groups.This analysis suggests that in patients with a higher FN risk, such as the elderly patients of this study, lipegfilgrastim reduces not only the duration of severe neutropenia but also the incidence of FN.


Butts C.,Cross Cancer Institute | Socinski M.A.,UPMC Cancer Pavilion | Mitchell P.L.,Austin Hospital | Thatcher N.,Christie Hospital NHS Trust | And 18 more authors.
The Lancet Oncology | Year: 2014

Background: Effective maintenance therapies after chemoradiotherapy for lung cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific cancer immunotherapy tecemotide improves survival in patients with stage III unresectable non-small-cell lung cancer when given as maintenance therapy after chemoradiation. Methods: The phase 3 START trial was an international, randomised, double-blind trial that recruited patients with unresectable stage III non-small-cell lung cancer who had completed chemoradiotherapy within the 4-12 week window before randomisation and received confirmation of stable disease or objective response. Patients were stratified by stage (IIIA vs IIIB), response to chemoradiotherapy (stable disease vs objective response), delivery of chemoradiotherapy (concurrent vs sequential), and region using block randomisation, and were randomly assigned (2:1, double-blind) by a central interactive voice randomisation system to either tecemotide or placebo. Injections of tecemotide (806 μg lipopeptide) or placebo were given every week for 8 weeks, and then every 6 weeks until disease progression or withdrawal. Cyclophosphamide 300 mg/m2 (before tecemotide) or saline (before placebo) was given once before the first study drug administration. The primary endpoint was overall survival in a modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00409188. Findings: From Feb 22, 2007, to Nov 15, 2011, 1513 patients were randomly assigned (1006 to tecemotide and 507 to placebo). 274 patients were excluded from the primary analysis population as a result of a clinical hold, resulting in analysis of 829 patients in the tecemotide group and 410 in the placebo group in the modified intention-to-treat population. Median overall survival was 25·6 months (95% CI 22·5-29·2) with tecemotide versus 22·3 months (19·6-25·5) with placebo (adjusted HR 0·88, 0·75-1·03; p=0·123). In the patients who received previous concurrent chemoradiotherapy, median overall survival for the 538 (65%) of 829 patients assigned to tecemotide was 30·8 months (95% CI 25·6-36·8) compared with 20·6 months (17·4-23·9) for the 268 (65%) of 410 patients assigned to placebo (adjusted HR 0·78, 0·64-0·95; p=0·016). In patients who received previous sequential chemoradiotherapy, overall survival did not differ between the 291 (35%) patients in the tecemotide group and the 142 (35%) patients in the placebo group (19·4 months [95% CI 17·6-23·1] vs 24·6 months [18·8-33·0], respectively; adjusted HR 1·12, 0·87-1·44; p=0·38). Grade 3-4 adverse events seen with a greater than 2% frequency with tecemotide were dyspnoea (49 [5%] of 1024 patients in the tecemotide group vs 21 [4%] of 477 patients in the placebo group), metastases to central nervous system (29 [3%] vs 6 [1%]), and pneumonia (23 [2%] vs 12 [3%]). Serious adverse events with a greater than 2% frequency with tecemotide were pneumonia (30 [3%] in the tecemotide group vs 14 [3%] in the placebo group), dyspnoea (29 [3%] vs 13 [3%]), and metastases to central nervous system (32 [3%] vs 9 [2%]). Serious immune-related adverse events did not differ between groups. Interpretation: We found no significant difference in overall survival with the administration of tecemotide after chemoradiotherapy compared with placebo for all patients with unresectable stage III non-small-cell lung cancer. However, tecemotide might have a role for patients who initially receive concurrent chemoradiotherapy, and further study in this population is warranted. Funding: Merck KGaA (Darmstadt, Germany). © 2014 Elsevier Ltd.


PubMed | University of Warmia and Mazury, University of Medicine and Pharmacy, Cluj-Napoca, Maria Curie Sklodowska University, University of Duisburg - Essen and 16 more.
Type: Clinical Trial, Phase III | Journal: The Lancet. Oncology | Year: 2014

Effective maintenance therapies after chemoradiotherapy for lung cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific cancer immunotherapy tecemotide improves survival in patients with stage III unresectable non-small-cell lung cancer when given as maintenance therapy after chemoradiation.The phase 3 START trial was an international, randomised, double-blind trial that recruited patients with unresectable stage III non-small-cell lung cancer who had completed chemoradiotherapy within the 4-12 week window before randomisation and received confirmation of stable disease or objective response. Patients were stratified by stage (IIIA vs IIIB), response to chemoradiotherapy (stable disease vs objective response), delivery of chemoradiotherapy (concurrent vs sequential), and region using block randomisation, and were randomly assigned (2:1, double-blind) by a central interactive voice randomisation system to either tecemotide or placebo. Injections of tecemotide (806 g lipopeptide) or placebo were given every week for 8 weeks, and then every 6 weeks until disease progression or withdrawal. Cyclophosphamide 300 mg/m(2) (before tecemotide) or saline (before placebo) was given once before the first study drug administration. The primary endpoint was overall survival in a modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00409188.From Feb 22, 2007, to Nov 15, 2011, 1513 patients were randomly assigned (1006 to tecemotide and 507 to placebo). 274 patients were excluded from the primary analysis population as a result of a clinical hold, resulting in analysis of 829 patients in the tecemotide group and 410 in the placebo group in the modified intention-to-treat population. Median overall survival was 25.6 months (95% CI 22.5-29.2) with tecemotide versus 22.3 months (19.6-25.5) with placebo (adjusted HR 0.88, 0.75-1.03; p=0.123). In the patients who received previous concurrent chemoradiotherapy, median overall survival for the 538 (65%) of 829 patients assigned to tecemotide was 30.8 months (95% CI 25.6-36.8) compared with 20.6 months (17.4-23.9) for the 268 (65%) of 410 patients assigned to placebo (adjusted HR 0.78, 0.64-0.95; p=0.016). In patients who received previous sequential chemoradiotherapy, overall survival did not differ between the 291 (35%) patients in the tecemotide group and the 142 (35%) patients in the placebo group (19.4 months [95% CI 17.6-23.1] vs 24.6 months [18.8-33.0], respectively; adjusted HR 1.12, 0.87-1.44; p=0.38). Grade 3-4 adverse events seen with a greater than 2% frequency with tecemotide were dyspnoea (49 [5%] of 1024 patients in the tecemotide group vs 21 [4%] of 477 patients in the placebo group), metastases to central nervous system (29 [3%] vs 6 [1%]), and pneumonia (23 [2%] vs 12 [3%]). Serious adverse events with a greater than 2% frequency with tecemotide were pneumonia (30 [3%] in the tecemotide group vs 14 [3%] in the placebo group), dyspnoea (29 [3%] vs 13 [3%]), and metastases to central nervous system (32 [3%] vs 9 [2%]). Serious immune-related adverse events did not differ between groups.We found no significant difference in overall survival with the administration of tecemotide after chemoradiotherapy compared with placebo for all patients with unresectable stage III non-small-cell lung cancer. However, tecemotide might have a role for patients who initially receive concurrent chemoradiotherapy, and further study in this population is warranted.Merck KGaA (Darmstadt, Germany).


Clemens M.R.,Klinikum Mutterhaus de Borromaerinnen GmbH | Gladkov O.A.,Chelyabinsk Regional Clinical Oncology Dispensary | Gartner E.,Barbara Ann Karmanos Cancer Institute | Vladimirov V.,Pyatigorsk Oncology Dispensary | And 4 more authors.
Breast Cancer Research and Treatment | Year: 2015

The objective of this study was to assess the efficacy and tolerability of YM155, a survivin suppressor, in combination with docetaxel, compared with docetaxel alone in patients with HER2-negative metastatic breast cancer. This phase II, multicenter, open-label, 2-arm study randomized patients (≥18 years) with histologically or cytologically confirmed stage IV HER2-negative metastatic breast cancer and ≥1 measurable lesion, to receive docetaxel alone or docetaxel plus YM155. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), duration of response (DOR), clinical benefit rate (CBR), time to response (TTR), biomarker assessment, and analysis of circulating tumor cells. Patients were women diagnosed with HER2-negative breast cancer; most had received prior drug therapies. The median PFS was 8.4 months with YM155 plus docetaxel (n = 50) and 10.5 months with docetaxel alone (n = 51; HR 1.53; 95 % CI 0.83, 2.83; P = 0.176). No statistically significant differences were observed for secondary endpoints, although slightly greater OS (630 vs 601 days; P = 0.768), CBR (84.3 vs 82.0 %; P = 0.855), DOR, and TTR were observed with docetaxel alone compared with YM155 plus docetaxel, whereas ORR was similar (25.5 vs 26.0). The most common TEAEs observed with YM155 plus docetaxel compared with docetaxel alone were neutropenia (83.3 vs 84.3 %), alopecia (62.5 vs 52.9 %), fatigue (50 vs 41.2 %), and nausea (37.5 vs 41.2 %). Although YM155 is a novel drug that suppresses survivin, YM155 plus docetaxel exhibited no statistically significant differences in endpoints compared with docetaxel alone. The combination regimen was well tolerated. © 2014, The Author(s).


Gladkov O.A.,Chelyabinsk Regional Clinical Oncology Dispensary | Buchner A.,Merckle GmbH | Bias P.,Teva Ratiopharm | Muller U.,Teva Ratiopharm | Elsasser R.,Teva Ratiopharm
Supportive Care in Cancer | Year: 2016

Purpose: Lipegfilgrastim is a once-per-cycle glycoPEGylated granulocyte colony-stimulating factor (G-CSF). Noninferiority of lipegfilgrastim versus pegfilgrastim was demonstrated in a phase III trial in chemotherapy (CTx)-naïve breast cancer patients. Secondary outcomes relating to treatment burden are reported here. Methods: Patients with high-risk stage II, III, or IV breast cancer were randomized to receive lipegfilgrastim 6 mg (n = 101) or pegfilgrastim 6 mg (n = 101) subcutaneously on day 2 of each CTx cycle. Doxorubicin 60 mg/m2 plus docetaxel 75 mg/m2 commenced on day 1, for up to four cycles. Secondary end points included days in the hospital or intensive care unit (ICU), use of intravenous antibiotics for febrile neutropenia (FN) or related infections, and measures of CTx delivery (dose delays, reductions, and omissions). Results: One lipegfilgrastim recipient and two pegfilgrastim recipients were hospitalized in cycle 1 because of FN or associated infection. The lipegfilgrastim-treated patient spent 1 day in the ICU for FN, and the two pegfilgrastim-treated patients were hospitalized for FN for 5 and 6 days, respectively. All hospitalized patients received antibiotics. An additional pegfilgrastim-treated patient received antibiotics but was not hospitalized. Most patients received CTx as scheduled; over 98 % received their planned doxorubicin and docetaxel doses in all cycles. In the lipegfilgrastim group, no patients had a CTx dose reduced or omitted; eight patients in the pegfilgrastim group had a CTx dose reduced or omitted during cycles 2–4. Conclusions: The burden of treatment associated with myelosuppressive CTx was similar in breast cancer patients treated with lipegfilgrastim or pegfilgrastim. © 2015, Springer-Verlag Berlin Heidelberg.


PubMed | Teva Ratiopharm, Merckle GmbH and Chelyabinsk Regional Clinical Oncology Dispensary
Type: Clinical Trial, Phase III | Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer | Year: 2015

Lipegfilgrastim is a once-per-cycle glycoPEGylated granulocyte colony-stimulating factor (G-CSF). Noninferiority of lipegfilgrastim versus pegfilgrastim was demonstrated in a phase III trial in chemotherapy (CTx)-nave breast cancer patients. Secondary outcomes relating to treatment burden are reported here.Patients with high-risk stage II, III, or IV breast cancer were randomized to receive lipegfilgrastim 6 mg (n=101) or pegfilgrastim 6 mg (n=101) subcutaneously on day 2 of each CTx cycle. Doxorubicin 60 mg/m(2) plus docetaxel 75 mg/m(2) commenced on day 1, for up to four cycles. Secondary end points included days in the hospital or intensive care unit (ICU), use of intravenous antibiotics for febrile neutropenia (FN) or related infections, and measures of CTx delivery (dose delays, reductions, and omissions).One lipegfilgrastim recipient and two pegfilgrastim recipients were hospitalized in cycle 1 because of FN or associated infection. The lipegfilgrastim-treated patient spent 1 day in the ICU for FN, and the two pegfilgrastim-treated patients were hospitalized for FN for 5 and 6 days, respectively. All hospitalized patients received antibiotics. An additional pegfilgrastim-treated patient received antibiotics but was not hospitalized. Most patients received CTx as scheduled; over 98% received their planned doxorubicin and docetaxel doses in all cycles. In the lipegfilgrastim group, no patients had a CTx dose reduced or omitted; eight patients in the pegfilgrastim group had a CTx dose reduced or omitted during cycles 2-4.The burden of treatment associated with myelosuppressive CTx was similar in breast cancer patients treated with lipegfilgrastim or pegfilgrastim.

Loading Chelyabinsk Regional Clinical Oncology Dispensary collaborators
Loading Chelyabinsk Regional Clinical Oncology Dispensary collaborators