A Multicenter, Prospective, Observational Study to Assess the Clinical Activity and Impact on Symptom Burden and Patients' Quality of Life in Patients with Advanced Soft Tissue Sarcomas Treated with Trabectedin in a Real-World Setting in Greece.

This non-interventional, multicenter, prospective study aimed to evaluate the real-world activity of trabectedin, and its impact on symptom burden and quality of life in patients with advanced soft tissue sarcoma (aSTS) treated in routine clinical settings in Greece. Patients with histologically confirmed aSTS newly initiated on trabectedin were enrolled. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS rate at 3 months, median PFS, objective response rate (ORR), disease control rate (DCR), overall survival (OS), and an assessment of the impact of treatment on health-related quality of life (HRQoL), cancer-related symptom burden and symptom interference with function, as well as all-cause treatment discontinuation rate. A total of 64 eligible patients from 13 Greek centers were evaluated. Patients received a median of three trabectedin cycles per patient (interquartile range [IQR]: 2.0-6.0). Median PFS was 6.6 months with 67.9% and 51.2% of patients free from progression at 3 and 6 months, respectively. ORR was 7.8% and DCR 21.9%. Median OS was 13.1 months. No significant changes from enrolment were noted in HRQoL scores. In total, 30 patients (46.9%) had at least one trabectedin-related adverse drug reaction (ADR) and 9 (14.1%) at least one serious ADR. The treatment discontinuation rate due to toxicity was 9.4%. These results suggest that trabectedin is an active treatment with clinically meaningful benefits in patients with aSTS with no new safety signals.

Prophylaxis of cancer-associated venous thromboembolism with low-molecular-weight heparin-tinzaparin: Real world evidence.

Thromboprophylaxis, as a preventive measure for cancer-associated thrombosis (CAT), may be beneficial for patients with active cancer and high-risk for thrombosis. The present post hoc analysis include a total of 407 patients enrolled in the Greek Management of Thrombosis study, who received thromboprophylaxis with tinzaparin. The objectives of the present analysis were: i) To obtain sufficient evidence for the administration of prophylaxis in patients with active cancer, irrespective of Khorana risk assessment model score; ii) to identify the selection criteria for both dose and duration of tinzaparin; and iii) to evaluate the efficacy and safety of tinzaparin administered for CAT prophylaxis. The main tumor types for the patients included in the present study were as follows: Lung (25.1%), pancreatic (14.3%), breast (9.1%), stomach (8.4%), colorectal (7.9%) and ovarian (7.6%). Furthermore, metastatic disease was observed in 69.5% of the patients. High thrombotic burden agents (HTBAs) were administered to 66.3% of the patients, and 17.4% received erythropoietin. A total of 43.7% of the patients exhibited a Khorana score <2. The results of the present study demonstrated that both the presence of metastatic disease and the use of HTBAs seemed to influence oncologists' decisions for the use of thromboprophylaxis in patients with active cancer, regardless of Khorana score. Tinzaparin, in dose expressed in the standard notation for heparins, i.e., anti-Xa factor international units (Anti-Xa IU), was administered at an intermediate dose (InterD; 8,000-12,000 Anti-Xa IU; once daily) to 52.4% of patients, while the remaining patients received a prophylactic dose (ProD; ≤4,500 Anti-Xa IU; once daily). The average duration of thromoprophylaxis was 5 months. Furthermore, a total of 14 (3.4%) thrombotic events and 6 (1.5%) minor bleeding events were recorded. A total of four thrombotic events were observed following an InterD treatment of tinzaparin, while 10 thrombotic events were observed following ProD treatment. The present study also demonstrated that an InterD of tinzaparin was administered more frequently to patients with a body mass index >30 kg/m2, a history of smoking and a history of metastatic disease, along with administration of erythropoietin. InterD tinzaparin treatment was found to be potentially more efficacious and without safety concerns. The present study is a registered clinical trial (ClinicalTrials.gov code, NCT03292107; registration date, September 25, 2017).

The Impact of Thromboprophylaxis on the Survival of Patients with Advanced Pancreatic Cancer. The Pancreatic Cancer and Tinzaparin (PaCT) Study.

Pancreatic cancer (PaC) induces a prothrombotic and hypercoagulable state. The aim of this study was to investigate the effect of tinzaparin in combination with chemotherapy. The PaCT (pancreatic cancer and tinzaparin) study was a retrospective observational study that collected data regarding progression free survival (PFS) in advanced or metastatic PaC patients who received thromboprophylaxis with tinzaparin during chemotherapy with nab-paclitaxel (N) and gemcitabine (G). The primary end point was to compare, from already published data, the PFS of patients receiving thromboprophylaxis with tinzaparin with the PFS of patients receiving chemotherapy with N-G but no thromboprophylaxis. Secondary end points were efficacy and safety of anticoagulation. In total, 110 PaC patients, 93% with advanced or metastatic disease, treated with N-G and tinzaparin (10,291 ± 1176 Anti-Xa IU, OD, median duration 8.7, IQR: 5.6-11.9 months) were enrolled. Of these, 52% were males and; the median age was 68 (40-86 years). The tumor was located to in the pancreatic head at in 45% of the patients. The median PFS was 7.9 months (IQR: 5.0-11.8 months). Out of 14 similar studies (involving 2994 patients) identified via systematic search, it was determined that the weighted PFS of patients receiving N-G but no anticoagulation was 5.6 months. Therefore, patients receiving tinzaparin had 39.54% higher PFS than patients without thromboprophylaxis (p < 0.05). During the follow-up period of 18.3 ± 11.7 months, three (2.7%) thrombotic events were recorded while two clinically relevant non-major bleeding events occurred (1.9%). In conclusion, PFS in advanced PaC patients undergoing chemotherapy is positively impacted by anticoagulation. Thromboprophylaxis with tinzaparin in treatment dose is efficient and safe.

Real-World Data on Thromboprophylaxis in Active Cancer Patients: Where Are We? Are We Getting There?

Background: Cancer patients are at high risk for cancer-associated thrombosis (CAT). CAT is the second leading cause of death in these patients but it can be preventable with thromboprophylaxis. Patients and Methods: An observational, prospective, multicenter study aiming to record CAT management in clinical practice was conducted by the Hellenic Society of Medical Oncology (HeSMO). Results: A total of 426 active cancer patients (mean age 65.3 years, mean BMI: 26.1 kg/m2) who received thromboprophylaxis, were included from 18 oncology units. Tumor types were lung 25.1%, pancreas 13.9%, breast 8.7%, stomach 8.5%, ovarian 7.8%, and others 36%, while 69% had metastases. A total of 71% had a Khorana score ≤2 and 61% received High Thrombotic Risk Chemotherapy Agents (HTRCAs, e.g., platinum). For thromboprophylaxis patients received mainly Low Molecular Weight Heparins (LMWHs), on higher than prophylactic doses in 50% of cases. Overall, 16 (3.8%) thrombotic events and 6 (1.4%) bleeding events were recorded. Notably, patients on higher doses of LMWHs compared to patients who received standard prophylactic doses had 70% lower odds to develop thrombotic events (OR: 0.3, 95% CI: 0.10-1.0, p = 0.04). Conclusion: CAT is an important issue in oncology. Along with the Khorana score, factors as metastasis and use of HTRCAs should also be taken into consideration. Thromboprophylaxis for active cancer patients with LMWHs, even on higher doses is safe and efficient.

Management of Cancer-associated Thrombosis (CAT): Symptomatic or Incidental.

BACKGROUND: Cancer-associated thrombosis (CAT), the second leading cause of death in patients with cancer can be treated with low molecular weight heparin (LMWH) according to guidelines. PATIENTS AND METHODS: A multicenter prospective observational study was carried out to record anti-thrombotic treatment practice, assess thrombosis recurrence and bleeding, and identify potential risk factors. Adult patients from 18 Oncology Departments throughout Greece were followed-up for 12 months. RESULTS: A total of 120 patients with CAT receiving anticoagulant treatment were enrolled (35% incidental); 85% were treated for more than 6 months, 95.8% were treated with tinzaparin and smaller percentages with other agents. Thrombosis recurred in three patients and there was minor bleeding in four patients. Bleeding was associated with high body mass index (>35 kg/m2), trauma history, renal insufficiency and bevacizumab use. CONCLUSION: Incidental thrombosis contributes significantly to CAT burden. Long-term use of LMWH seems to be effective and safe. Several risk factors associated with bleeding should be considered during anti-coagulation therapy planning.

The continuation of bevacizumab following disease progression in patients with metastatic colorectal cancer offers a survival benefit.

BACKGROUND/AIMS: There is little information in the literature on the use of bevacizumab (BV) combination chemotherapy in multiple lines with regimens including irinotecan and oxaliplatin, in metastatic colorectal cancer (mCRC) patients with disease progression. The aim of this small retrospective institutional study is to compare the efficacy and safety of the continuation of BV in combination with various chemotherapeutic agents, within the framework of multiple line therapy in progressed mCRC patients. METHODOLOGY: Our retrospective study included 21 patients with mCRC that had received at least one course of irinotecan-based or oxaliplatin-based chemotherapy with BV before disease progression. BV treatment was continuously dispensed after disease progression. Subgroup analysis was performed in terms of age, site of metastases, spread and co-morbidity. RESULTS: The median overall survival (OS) was 23+ months (range 4-51 months) with no statistically significant differences between the aforementioned subgroups of patients, except from the subgroup according to spread (p=0.044). Time to progression was 17 months. Anemia (all grades) was reported in 33.3% of the patients, while hemorrhage and thrombosis were reported in 28.6% and 14.3%, respectively. CONCLUSIONS: Multiple line treatment in advanced colorectal cancer, including BV combined with standard chemotherapy, may improve OS with an acceptable toxicity profile in patients with mCRC after disease progression.

Survival benefit with the combination of docetaxel, gemcitabine and erlotinib in advanced and/or metastatic pancreatic cancer patients.

BACKGROUND/AIMS: Although research on new effective treatments against pancreatic cancer is intense, limited therapeutic schemes are currently approved. The aim of the present study was to record the efficacy and safety of gemcitabine-erlotinib plus docetaxel combination therapy in patients with advanced and/or metastatic pancreatic cancer. METHODOLOGY: Twenty-five chemotherapy naive patients with histologically confirmed unresectable pancreatic cancer and documented extrapancreatic metastases, received biweekly gemcitabine 1,500mg/m2 during a 28-day long cycle; daily erlotinib 100mg per os; and docetaxel 80mg/m2 as intravenous infusion administered every 15 days. Patients were monitored every 4 cycles for survival, adverse events and tumour response with Computed Tomography scans. RESULTS: Patients received 153 cycles in total, with a median of 7.64 cycles (range, 1-24). The median overall survival was 10 months and 45% of the patients reached and surpassed 1-year survival. No grade IV toxicities were recorded. The only grade III recorded toxicities were thrombopenia (4 patients, 16%), anaemia (1 patient, 4%) and neutropenia (1 patient, 4%). Overall the most frequently experienced adverse events were grade I anaemia (18 patients, 72%) and grade II rash (13 patients, 52%). CONCLUSIONS: Biweekly gemcitabine with erlotinib plus docetaxel administration is a practical alternative to pancreatic cancer treatment, presenting comparable results to weekly gemcitabine administration.

Small-cell lung cancer: an unusual therapeutic approach with more than 10-year overall survival. Case report and review of the literature.

Small-cell lung cancer is the most aggressive lung cancer, with a dismal prognosis. The authors present a case report of a patient with limited-stage small-cell lung cancer who underwent a thoracotomy for diagnostic purposes, with the diagnosis being made after surgical excision. Combination chemotherapy remains the cornerstone of treatment for both limited and extensive disease. Radiotherapy has been established as an adjunct to chemotherapy in limited-stage disease, while in extensive-stage disease it is mostly reserved for the treatment of brain metastases. As for surgery, the potential benefits of resection are predominantly seen in patients who present with a solitary pulmonary nodule. Since small-cell lung cancer becomes highly resistant to chemotherapy, second-line chemotherapeutic schemes are used for disease progression, with topotecan being the highlighted agent. Despite the unusual therapeutic approach, where surgery was preferred over the standard diagnostic and staging procedures, the patient's more than ten years' survival makes this case presentation a very interesting one.

Heart and tumors: location, metastasis, clinical manifestations, diagnostic approaches and therapeutic considerations.

Cardiac neoplasms, whether primary or secondary, are more and more easily diagnosed in the present era. For the primary heart tumors, myxomas and sarcomas constitute the most common neoplasms, whereas for the secondary ones, lung cancer constitutes the most common primary location. Cardiac neoplasms may involve the endocardium, the myocardium, the epicardium, the valves or any combination of these. Their clinical manifestations are not specific and depend on their anatomic location and size. Diagnosis of cardiac neoplasms has become more feasible with the use of echocardiography and other imaging techniques (computed tomography and magnetic resonance). The major problem, however, still remains that most diagnoses are late, especially for malignant tumors. For resectable tumors, surgery remains the mainstay of treatment, whereas for metastatic disease palliative treatment remains the only therapeutic option. This paper reviews the types of heart tumors, their clinical symptoms, the diagnostic approaches and the therapeutic tools used by physicians.

The combination of estramustine, vinorelbine, and mitoxantrone in hormone-refractory prostate cancer: a Phase II feasibility study conducted by the Hellenic Cooperative Oncology Group.

OBJECTIVES: To evaluate the safety profile and therapeutic value of the combination of estramustine, mitoxantrone, and vinorelbine in the treatment of hormone-refractory prostate cancer. METHODS: Fifty-two patients with hormone-refractory prostate cancer were included in the study. Median age was 70 years (range, 49 to 100 years), World Health Organization performance status ranged from 0 to 2. The treatment schedule consisted of estramustine capsules (140 mg 3 times daily on days 1 to 3 and days 8 to 10 per os), intravenous mitoxantrone (12 mg/m2 on day 2), and intravenous vinorelbine (25 mg/m2 on day 2 and day 9), given in a 3-week cycle. RESULTS: Thirty-one percent of patients with measurable soft-tissue disease demonstrated an objective response, which included six complete and ten partial responses in all involved organs (bone responses not included). Twenty-nine patients (56%) had a greater than 50% reduction in serum prostate-specific antigen level. The median duration of response was 6.9 months, and the median survival for all patients was 14.5 months. CONCLUSIONS: The combination of estramustine, vinorelbine, and mitoxantrone is safe, well tolerated, and relatively active in patients with hormone-refractory prostate cancer.