Sequential treatment of metastatic renal cell carcinoma patients after first-line vascular endothelial growth factor targeted therapy in a real-world setting: epidemiologic, noninterventional, retrospective-prospective cohort multicentre study.

PURPOSE: The purpose of our study was to determine whether data on the clinical effectiveness of second-line therapy collected in a real-world setting provide additional valuable information on the optimal sequence of metastatic renal cell carcinoma (mRCC) treatment. METHODS: Patients diagnosed with mRCC who were treated with at least one dose of first-line vascular endothelial growth factor (VEGF)-targeted therapy with either sunitinib or pazopanib and with at least one dose of second-line everolimus, axitinib, nivolumab, or cabozantinib were included. The efficacy of different treatment sequences was analyzed based on the time to the second objective disease progression (PFS2) and the time to the first objective disease progression (PFS). RESULTS: Data from 172 subjects were available for analysis. PFS2 was 23.29 months. The 1-year PFS2 rate was 85.3%, and the 3-year PFS2 rate was 25.9%. The 1-year overall survival rate was 97.0%, and the 3-year overall survival rate was 78.6%. Patients with a lower IMDC prognostic risk group had a significantly (p < 0.001) longer PFS2. Patients with metastases in the liver had a shorter PFS2 than patients with metastases in the other sites (p = 0.024). Patients with metastases in the lungs and lymph nodes (p = 0.045) and patients with metastases in the liver and bones (p = 0.030) had lower PFS2 rates than patients with metastases in other sites. CONCLUSIONS: Patients with a better IMDC prognosis have a longer PFS2. Metastases in the liver lead to a shorter PFS2 than metastases in other sites. One metastasis site means a longer PFS2 than 3 or more metastasis sites. Nephrectomy performed in an earlier stage of disease or metastatic setting means higher PFS and higher PFS2. No PFS2 difference was found between different treatment sequences of TKI-TKI or TKI-immune therapy.

Retrospective analysis of the impact of anthracycline dose reduction and chemotherapy delays on the outcomes of early breast cancer molecular subtypes.

BACKGROUND: The objective of study was to determine the effect of anthracycline dose reduction and chemotherapy delays on 5-year overall survival in patients with stage I-III breast cancer, to establish the impact of molecular subtypes on the anthracycline modification effects and to analyze reasons for such chemotherapy scheme modifications. METHODS: Medical records of patients with stage I-III breast cancer were reviewed. Inclusion criteria involved stage I- III breast carcinoma; radical surgery performed and 4 courses of AC regimen (doxorubicin and cyclophosphamide), or at least 6 courses of FAC regimen (fluorouracil, doxorubicin and cyclophosphamide) completed; no neoadjuvant chemotherapy applied; no taxane group medications administered; medical records maintain comprehensive data on treatment and follow-up. 5- year overall survival were analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Significant 3.17 times higher death risk at 5 year period in patients who experienced anthracycline dose reduction compared with patients who did not experience any modifications was established (HR = 3.17, 95% CI 1.7-5.9, p < 0.001). Increased death risk in patients who experienced both chemotherapy dose reduction and treatment delays compared with patients who did not experience any modifications was also established (HR = 2.76, 95% CI 1.3-5.6, p < 0.05). 5- year overall survival was affected by anthracycline dose reduction by more than 15% in ER-HER2- group (80% v. 55.6%, p = 0.015), ER + HER2- group (90.7% v. 64.9%, p < 0.01) and ER+/-HER2+ group (100% v. 84.4%, p = 0.019). 5-year overall survival was affected by chemotherapy delays more than 2 cycles in ER-HER2- group (79.2% v. 51.4%, p = 0.002), ER + HER2- group (86.3% v. 58.8%, p = 0.014) and there was no difference in ER+/-HER2+ group. Main reasons for chemotherapy scheme modifications (in decreasing order) were the following: neutropenia, modifications with no objective medical reasons, thrombocytopenia, anaemia, fatigue, infection. CONCLUSIONS: Anthracycline dose reduction in patients with stage I- III breast cancer were associated with higher mortality risk and significantly decreased 5- year absolute survival in all molecular subtypes. Chemotherapy delays alone were not associated with decreased survival only in HER2 positive subtype. The most common reason for dose reduction or chemotherapy delays was neutropenia.

Retrospective analysis of the impact of platinum dose reduction and chemotherapy delays on the outcomes of stage III ovarian cancer patients.

BACKGROUND: Ovarian cancer is a common gynaecological malignancy still remaining a challenge to treat. The objective of this study was to evaluate the impact of platinum dose reduction and chemotherapy delays on progression free survival and overall survival in patients with stage III ovarian cancer and to analyze reasons for such chemotherapy scheme modifications. METHODS: Medical records of patients with FIGO stage III ovarian cancer were reviewed. Inclusion criteria involved FIGO stage III epithelial ovarian carcinoma; cytoreductive surgery performed and 6 courses of platinum-based chemotherapy completed; no neoadjuvant chemotherapy applied; and no history of previous malignancies. Progression free survival and overall survival were analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Significant 3.3 times higher death risk in patients who experienced only chemotherapy delays compared with patients who did not experience any chemotherapy scheme modifications was established (HR = 3.3, 95% Cl: 1.2 - 8.5, p = 0.016). Increased death risk in patients who experienced only chemotherapy delays compared with patients who experienced both chemotherapy delays and platinum dose reduction was also established (HR = 2.3, 95% Cl: 1.1 - 4.8, p = 0.021). Main reasons for chemotherapy scheme modifications (in decreasing order) were the following: neutropenia, modifications with no objective medical reasons, renal disorders, anaemia, poor performance status, gastrointestinal symptoms and neuropathy. Overall survival in patients who experienced chemotherapy scheme modifications with no objective medical reasons was non-inferior than in patients who did not experience any chemotherapy scheme modifications. CONCLUSIONS: Chemotherapy delays in patients with FIGO stage III ovarian cancer caused lower overall survival. The most common reason for chemotherapy scheme modifications was neutropenia.

Guidelines for diagnostics and treatment of aromatase inhibitor-induced bone loss in women with breast cancer: a consensus of Lithuanian medical oncologists, radiation oncologists, endocrinologists, and family medicine physicians.

The aim of this article is to inform about cancer treatment-induced bone loss, to identify patients at risk and those that can benefit from bone targeted treatment as well as highlight the importance of the multidisciplinary approach in the bone health in cancer care. Patients with breast cancer treated or intended to be treated with aromatase inhibitors belong to a high-risk group because their fracture risk increases up to 30% due to a significant decrease in bone mineral density within 6-12 months after the start of hormonal treatment. To evaluate bone status and predict risk for fractures, lateral thoracic and lumbar spine X-ray imaging, bone mineral density measurement by dual energy X-ray absorptiometry at the lumbar spine L1-L4 vertebrae and/or hip and fracture risk factors assessment are mandatory tests prior to hormonal treatment. Morbidity and mortality associated with bone loss can be prevented with appropriate screening, lifestyle interventions, and therapy. Algorithm for the management of bone health in breast cancer patients was established in Lithuania to screen patients with increased risk for bone loss and to provide adequate specific osteoporosis treatment.

An open-label multicenter safety, tolerability, and efficacy study of recombinant granulocyte colony-stimulating factor in the prevention of neutropenic complications in breast cancer patients.

UNLABELLED: The primary objective of this open-label, two chemotherapy arm, phase 4 study was to evaluate the safety and efficacy of newly developed recombinant granulocyte colony-stimulating factor (rG-CSF) used to prevent neutropenia-related complications in patients with metastatic breast cancer treated with docetaxel (75 mg/m(2)) and doxorubicin (50 mg/m(2)) or docetaxel (100 mg/m(2)) alone. MATERIAL AND METHODS: A total of 50 patients who were treated with a maximum of 6 cycles of either docetaxel-doxorubicin (36 patients) or docetaxel alone (14 patients) every 21 days were recruited from 3 centers in Lithuania. All the patients received study medication rG-CSF at a dosage of 5 µg/kg per day (Sicor Biotech UAB, Teva Group) from day 2 of each cycle and continued for minimum 5 days or until absolute neutrophil count reached ≥1.5×10(9)/L. RESULTS: A total of 611 adverse events were reported. Most of them were related to myelotoxic chemotherapy. Two patients withdrew due to adverse events (neuropathy and bone pain). One patient died possibly because of pulmonary thromboembolism. The most frequently reported adverse events related to study drug in the docetaxel-doxorubicin and docetaxel groups were leukocytosis (22% and 21%, respectively), bone pain (19% and 21%, respectively), and headache (8% and 14%, respectively). The incidence of grade 4 neutropenia in both the groups was 47% and 29%, respectively, in all cycles and 42% and 21%, respectively, in cycle 1. The incidence of febrile neutropenia was 8% in cycle 1 and 14% across all cycles. The mean duration of febrile neutropenia was 2.1 days (SD, 1.9) in cycle 1 and 2.14 days (SD 2.0) across all cycles in both the treatment groups. CONCLUSION: This study provide data that the study drug rG-CSF has the expected safety and could be an efficacious medication to decrease the risk of febrile neutropenia and related complications of myelosuppressive chemotherapy in patients with metastatic breast cancer.

[Impact of p53 protein and HER2 overexpression on survival of patients with stage II breast cancer]. / HER2 receptoriu ir p53 baltymo padidejusios raiskos itaka II stadijos kruties veziu serganciu moteru gyvenimo trukmei.

OBJECTIVE: To assess the prognostic significance and impact of p53 protein and human epidermal growth factor receptor 2 (HER2) overexpression on 5-year survival in young patients with stage II breast cancer (aged less than 50 years). MATERIAL AND METHODS: Material from medical records and archived tumor tissues from 34 young women diagnosed with stage II breast cancer and obtained between 2001 and 2003 was analyzed retrospectively. Twelve (35%) patients died from breast cancer. Using archived tumor tissues, p53 protein and HER2 over-expression was determined immunohistochemically. Using medical records, and adjuvant chemotherapy, adequacy of anthracycline dose, and hormonotherapy administered for the patients were analyzed. RESULTS: p53 protein and HER2 overexpression was documented in 20.6% and 26.4% of women, respectively. Kaplan-Meier survival analysis showed that patients with tumors positive for p53 protein and negative estrogen receptors, and treated with an inadequate dose of anthracyclines died within shorter period after diagnosis (log-rank P=0.016, log-rank P=0.027, log-rank P=0.013, respectively). There were no significant associations between HER2 overexpression and 5-year survival in this population (log-rank P=0.51). Multivariate analysis revealed that an inadequate dose of anthracyclines (P=0.028) was the only independent factor for poor outcome. CONCLUSIONS: p53 protein overexpression, negative estrogen receptors in tissue samples, and inadequate chemotherapy with anthracyclines were associated with reduced overall survival in young women with stage II breast cancer. Inadequate adjuvant therapy with anthracyclines was the only independent prognostic factor.

[Safety and efficacy study of the recombinant granulocyte colony-stimulating factor for prevention of neutropenia and neutropenia-related complications in women with metastatic breast cancer receiving docetaxel/doxorubicin]. / Rekombinacinio granuliocitu kolonijas stimuliuojamojo faktoriaus, vartojamo neutropenijos ir neutropenijos sukeltu komplikaciju profilaktikai serganciosioms metastazavusiu kruties veziu ir gydomoms docetakseliu ir doksorubicinu, saugumo ir veiksmingumo tyrimas.

BACKGROUND: We evaluated efficacy and safety of recombinant granulocyte-colony stimulating factor (rGCSF) used as primary prophylaxis to prevent neutropenia and neutropenia-related complications induced by docetaxel and doxorubicin chemotherapy in patients with metastatic breast cancer. PATIENTS AND METHODS: Three centers in Lithuania enrolled 36 patients who received rGCSF (5 microg/kg/d) on day 2 of each 21-day chemotherapy with docetaxel 75 mg/m(2) and doxorubicin 50 mg/m(2) (AT) starting in the first cycle. Treatment regimen was repeated for up to six cycles. RESULTS: Leukocytosis, bone pain, and headache were the most frequent adverse events, with incidence rates of 22%, 19%, and 8%, respectively. Adverse events were typical for rGCSF in this patient population. Overall incidence rate of febrile neutropenia was 14%. The mean duration of febrile neutropenia episodes across cycles was 2.14 days. Incidence of chemotherapy delay was 2%. There was no reduction in chemotherapy dose due to expected toxicity or side effects. Intravenous antibiotics for the treatment of febrile neutropenia were needed in 19% of cases. Quality-of-life assessment shows a significant improvement in emotional functioning and a significant decrease in pain score. The efficacy profile of rGCSF observed in the present study was comparable with that of other rGCSF products previously described in the published scientific literature. CONCLUSIONS: The primary prophylaxis of neutropenia and its complications by rGCSF was safe and effective for women with metastatic breast cancer who received chemotherapy with docetaxel and doxorubicin.