Background: Guidelines addressing the management of venous thromboembolism (VTE) in cancer patients are heterogeneous and their implementation has been suboptimal worldwide. Objectives: To establish ...a common international consensus addressing practical, clinically relevant questions in this setting. Methods: An international consensus working group of experts was set up to develop guidelines according to an evidence‐based medicine approach, using the GRADE system. Results: For the initial treatment of established VTE: low‐molecular‐weight heparin (LMWH) is recommended 1B; fondaparinux and unfractionated heparin (UFH) can be also used 2D; thrombolysis may only be considered on a case‐by‐case basis Best clinical practice (Guidance); vena cava filters (VCF) may be considered if contraindication to anticoagulation or pulmonary embolism recurrence under optimal anticoagulation; periodic reassessment of contraindications to anticoagulation is recommended and anticoagulation should be resumed when safe; VCF are not recommended for primary VTE prophylaxis in cancer patients Guidance. For the early maintenance (10 days to 3 months) and long‐term (beyond 3 months) treatment of established VTE, LMWH for a minimum of 3 months is preferred over vitamin K antagonists (VKA) 1A; idraparinux is not recommended 2C; after 3–6 months, LMWH or VKA continuation should be based on individual evaluation of the benefit‐risk ratio, tolerability, patient preference and cancer activity Guidance. For the treatment of VTE recurrence in cancer patients under anticoagulation, three options can be considered: (i) switch from VKA to LMWH when treated with VKA; (ii) increase in LMWH dose when treated with LMWH, and (iii) VCF insertion Guidance. For the prophylaxis of postoperative VTE in surgical cancer patients, use of LMWH o.d. or low dose of UFH t.i.d. is recommended; pharmacological prophylaxis should be started 12–2 h preoperatively and continued for at least 7–10 days; there are no data allowing conclusion that one type of LMWH is superior to another 1A; there is no evidence to support fondaparinux as an alternative to LMWH 2C; use of the highest prophylactic dose of LMWH is recommended 1A; extended prophylaxis (4 weeks) after major laparotomy may be indicated in cancer patients with a high risk of VTE and low risk of bleeding 2B; the use of LMWH for VTE prevention in cancer patients undergoing laparoscopic surgery may be recommended as for laparotomy Guidance; mechanical methods are not recommended as monotherapy except when pharmacological methods are contraindicated 2C. For the prophylaxis of VTE in hospitalized medical patients with cancer and reduced mobility, we recommend prophylaxis with LMWH, UFH or fondaparinux 1B; for children and adults with acute lymphocytic leukemia treated with l‐asparaginase, depending on local policy and patient characteristics, prophylaxis may be considered in some patients Guidance; in patients receiving chemotherapy, prophylaxis is not recommended routinely 1B; primary pharmacological prophylaxis of VTE may be indicated in patients with locally advanced or metastatic pancreatic 1B or lung 2B cancer treated with chemotherapy and having a low risk of bleeding; in patients treated with thalidomide or lenalidomide combined with steroids and/or chemotherapy, VTE prophylaxis is recommended; in this setting, VKA at low or therapeutic doses, LMWH at prophylactic doses and low‐dose aspirin have shown similar effects; however, the efficacy of these regimens remains unclear 2C. Special situations include brain tumors, severe renal failure (CrCl < 30 mL min−1), thrombocytopenia and pregnancy. Guidances are provided in these contexts. Conclusions: Dissemination and implementation of good clinical practice for the management of VTE, the second cause of death in cancer patients, is a major public health priority.
Summary
Background
Recommendations for management of cancer‐related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low‐quality evidence. This ...international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagulation strategies.
Methods
Patients with cancer and VTE despite anticoagulant therapy were reported to the registry. Data on treatments, VTE events, major bleeding, residual thrombosis symptoms and death were collected for the following 3 months. Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes with different treatment strategies were compared with Cox proportional hazards regression.
Results
We registered 212 patients with breakthrough VTE. Of those, 59% had adenocarcinoma and 73% had known metastases. At the time of the breakthrough event, 70% were on low‐molecular‐weight heparin (LMWH) and 27% on a vitamin K antagonist (VKA); 70% had a therapeutic or supratherapeutic dose. After breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased in 31%, switched to another drug in 24%; and other management in 11%. During the following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence was less common with LMWH than with a VKA (hazard ratio HR, 0.28; 95% confidence interval CI, 0.11–0.70) but similar with unchanged or increased anticoagulant intensity (HR, 1.09; 95% CI, 0.45–2.63). The bleeding rate did not increase significantly with dose escalation.
Conclusion
Morbidity and mortality are high after recurrence of cancer‐related VTE despite anticoagulation. Further treatment appears to be more effective with LMWH than with a VKA.
Background: Although long‐term indwelling central venous catheters (CVCs) may lead to pulmonary embolism (PE) and loss of the CVC, there is lack of consensus on management of CVC‐related thrombosis ...(CRT) in cancer patients and heterogeneity in clinical practices worldwide. Objectives: To establish common international Good Clinical Practices Guidelines (GCPG) for the management of CRT in cancer patients. Methods: An international working group of experts was set up to develop GCPG according to an evidence‐based medicine approach, using the GRADE system. Results: For the treatment of established CRT in cancer patients, we found no prospective randomized studies, two non‐randomized prospective studies and one retrospective study examining the efficacy and safety of low‐molecular‐weight heparin (LMWH) plus vitamin K antagonists (VKAs). One retrospective study evaluated the benefit of CVC removal and two small retrospective studies were on thrombolytic drugs. For the treatment of symptomatic CRT, anticoagulant treatment (AC) is recommended for a minimum of 3 months; in this setting, LMWHs are suggested. VKAs can also be used, in the absence of direct comparisons of these two types of anticoagulants in this setting Guidance. The CVC can be kept in place if it is functional, well‐positioned and non‐infected and there is good resolution under close surveillance; whether the CVC is kept or removed, no standard approach in terms of AC duration has been established Guidance. For the prophylaxis of CRT in cancer patients, we found six randomized studies investigating the efficacy and safety of VKA vs. placebo or no treatment, one on the efficacy and safety of unfractionnated heparin, six on the value of LMWH, one double‐blind randomized and one non randomized study on thrombolytic drugs and six meta‐analyses of AC and CVC thromboprophylaxis. Type of catheter (open‐ended like the Hickman® catheter vs. closed‐ended catheter with a valve like the Groshong® catheter), its position (above, below or at the junction of the superior vena cava and the right atrium) and method of placement may influence the onset of CRT on the basis of six retrospective trials, four prospective non‐randomized trials, three randomized trials and one meta‐analysis. In light of these data: use of AC for routine prophylaxis of CRT is not recommended 1A; a CVC should be inserted on the right side, in the jugular vein, and distal extremity of the CVC should be located at the junction of the superior vena cava and the right atrium 1A. Conclusion: Dissemination and implementation of these international GCPG for the prevention and treatment of CRT in cancer patients at each national level is a major public health priority, needing worldwide collaboration.
Background
Anemia is often associated with a lower quality of life and less tolerance to treatments in cancer patients.
Objective
The aims of this retrospective study were to assess the biological ...(hemoglobin, Hb) and clinical (ECOG index) impact of ferric carboxymaltose (FCM) and to identify predictive factors of response in cancer patients with iron deficiency.
Methods
We included 133 patients with solid tumors who received at least one dose of FCM in 2015.
Results
At baseline, most patients had metastatic cancer (70%), were undergoing chemotherapy (82%), suffered from anemia (90%), and 72% had an ECOG 0–1 index. Mean Hb level was statistically higher at M1 (108.3 g/L ± 13.9), M2 (110.3 g/L ± 16.1), and M3 (111.7 g/L ± 12.6) than M0 (99.2 g/L ± 13.9). Mean ECOG score increased significantly at M1 (1.31 ± 0.80) and M2 (1.31 ± 0.87) compared to M0 (1.13 ± 0.80). Variations of ECOG index between M0 and M1 were independent of levels of Hb and ferritin at inclusion and pretreatment use of transfusion and ESAs. Increase of Hb level was higher in patients with Hb < 100 g/L, ferritinemia < 800 ng/ml, or transfused before inclusion. In multivariate analysis, an ECOG index of 0 was the only predictive factor of an increase of ECOG index and Hb level < 100 g/L and ferritinemia < 800 ng/ml were predictive of an increase in Hb.
Conclusion
Even though there was no improvement in ECOG index, this study did identify an increase of Hb for patients receiving FCM, indicating its potential benefit in iron-deficient cancer patients.
Abstract Purpose Data on long-term treatment with low-molecular-weight heparins (LMWH) in cancer patients treated for venous thromboembolism are scarce. Study objectives were to document the ...long-term clinical use of LMWH and patient perception in this setting. Methods Adult cancer patients receiving antineoplastic treatment or palliative care and LMWH for cancer associated venous thromboembolism (CAT) were eligible to participate in this prospective observational study. Main outcome was adherence to clinical practice guidelines based on recommended LMWH treatment doses for at least 3 months in the absence of severe renal insufficiency. Patients' perception of the treatment was assessed in an ancillary study using the Perception Anticoagulant Treatment Questionnaire (PACT-Q). Results Among 409 included cancer patients aged 65 ± 12.1 years, overall adherence to practice guidelines as defined in the protocol was 55.3% (226 patients). However, 98.0% of patients received a prescription for 3 months or more and mean LMWH treatment duration for VTE was 6.27 ± 0.15 months which meets guidelines recommendations. Main patients' expectations scored on a 1–5 scale were blood clots prevention (mean 3.94 ± 0.75), symptom relief (mean 3.98 ± 1.04) and ease of use (mean 4.22 ± 0.9). LMWH treatment appeared convenient (global score 79.7 ± 17.1 on a 0 to 100 scale) and 69.1% of patients were satisfied or very satisfied. Conclusion Despite incomplete strict adherence to guidelines, treatment duration with LMWH was adequate showing substantial progress in the management of CAT patients. Patients expectations were high while treatment was perceived convenient with a high degree of satisfaction.
Apart from myeloma, primary prophylaxis of venous thromboembolism (VTE) in ambulatory cancer patients treated with chemotherapy is underused, despite its proven benefit for pancreatic cancer and to a ...lesser extent for lung cancer. This prophylaxis has been showed to be effective for myeloma, pancreas but in absolute numbers these cancers lead to a few venous thromboembolic events. Up to date, VTE risk scores cannot be used as a discriminatory criterion to select a high-risk population that could really benefit from this prevention. VTE depends in part on oncogenic mutations of tumor cells that result in an imbalance between activation and inhibition pathways that are involved in venous thrombus formation. So, stratification of risk of VTE in cancer patients could be considered from a clinical and molecular point of view and result in a tailored prophylaxis. This "personalized medicine" that is currently used for the anti-tumor treatment of many cancers and hematological malignancies, could lead to a more effective prophylaxis of VTE in cancer patients.
Purpose
Our objective was to compare patient’s expectations to their experience and to identify factors predictive of patient’s perception of long-term LMWH for the treatment of cancer-associated ...thrombosis (CAT).
Methods
Results from the validated Perception Anticoagulant Treatment Questionnaires (PACTQ) completed before inclusion (PACTQ1 for expectations) and at the end (PACTQ2 for convenience and satisfaction) of the 6-month TROPIQUE study were studied with principal component analysis. Possible predictive factors of improved perception of LMWH treatment were analyzed with the Kruskall–Wallis test.
Results
Among 409 included patients treated with LMWH, 269 PACT-Q1 and 139 PACT-Q2 were evaluable for treatment perception. Patients had high expectations (A1–A7 score of 26.7 ± 3.5, max = 35). Treatment cost (A7 = 1.90 ± 1.31) and concern about a mistake in anticoagulation (A5 = 1.93 ± 1.12) had little importance while LMWH treatment was considered easy to use (A4 = 4.20 ± 0.93). Six-month treatment with LMWH was associated with a high rate of convenience (B1–B11, C1–C2 = 55.1 ± 8.38, max = 65) and a high satisfaction score (D1–D7 = 25.1 ± 4.32, max = 35). Patients’ confidence in treatment and perception of possible LMWH side effects were moderate while perception of autonomy and independence significantly improved at the end of the study compared to inclusion. PACT-Q2 satisfaction score was low in patients who experienced bleeding (PACT-Q2 24.1 ± 3.3 vs. 25.1 ± 4.3). LMWH twice daily tended to be found less convenient compared than once daily (53.3 ± 7.2 vs. 55.0 ± 8.3).
Conclusion
CAT patients had a good perception of the 6-month LMWH treatment when comparing expectations and experience. Using a quantitative scale validated in the general population for VTE and subcutaneous injection and including a large number of patients, bleeding complications and LMWH twice daily were associated with a nonsignificant trend towards a worsen perception.
In view of the lack of recommendations on central venous catheter (CVC)-associated thrombosis in cancer patients, we established guidelines according to the well-standardized Standards, Options and ...Recommendations methodology.
A literature review (1990–2007) on CVC-associated thrombosis was carried out. The guidelines were developed on the basis of the corresponding levels of evidence derived from analysis of the 36 of 175 publications selected. They were then peer reviewed by 65 independent experts.
For the prevention of CVC-associated thrombosis, the distal tip of the CVC should be placed at the junction between the superior cava vein and right atrium; anticoagulants are not recommended. Treatment of CVC-associated thrombosis should be based on the prolonged use of low-molecular weight heparins. Maintenance of the catheter is justified if it is mandatory, functional, in the right position, and not infected, with a favorable clinical evolution under close monitoring; anticoagulant treatment should then be continued as long as the catheter is present.
Several rigorous studies do not support the use of anticoagulants for the prevention of CVC-associated thrombosis. Treatment of CVC-associated thrombosis relies on the same principles as those applied in the treatment of established thrombosis in cancer patients.
Pancreatic cancer (PC) is a devastating malignancy with an overall 5-year survival of 8% for all stages combined. Most of the PC patients diagnosed have an advanced disease (40%) or metastatic stage ...(40%), which eliminates surgery as a potentially curative treatment. The disease course is often complicated by venous thromboembolism (VTE) events, which per se account for significant morbidity and mortality, with significantly worsen survival. PC is associated with the highest risk of VTE among all cancer patients. We review the literature data to address the incidence and clinical outcomes of VTE in PC patients. VTE incidence varies from 5 to 41% according to epidemiological studies and is as high as 57% in postmortem series. Since 2013, international clinical practice guidelines recommend primary thromboprophylaxis with a grade 1B level of evidence as an adjuvant therapy in advanced PC. A recent meta-analysis of randomized controlled trials investigating the benefit and risk of low-molecular-weight heparins (LMWH) in ambulatory advanced PC patients under chemotherapy showed that the incidence of VTE was 2.1% in patients treated with LMWH and 11.2% in controls (risk ratio, 0.18; 95% CI, 0.083-0.39; P<0.0001). In conclusion, improved earlier diagnosis and effective management of VTE, a frequent and life-threatening complication in PC, is warranted to improve PC patient outcomes.
The aim of the RESGEX study was to compare the efficacy and safety of the anti-epidermal growth factor receptor (anti-EGFR) antibody tomuzotuximab against cetuximab both in combination with ...chemotherapy in patients with recurrent and/or metastatic squamous cell cancer of the head and neck in the first-line treatment.
In this phase II trial 240 patients were equally randomized for six cycles to receive either tomuzotuximab (initial dose 990 mg then 720 mg) weekly and cisplatin 100 mg/m2 and fluorouracil (5-FU; 1000 mg/m2/day, days 1-4) every 3 weeks or cetuximab (400 mg/m2 subsequent 250 mg/m2) weekly with the same chemotherapeutic backbone followed by antibody maintenance treatment. The primary endpoint was progression-free survival.
Median progression-free survival was 6.5 months 95% confidence interval (CI) 5.9-7.9 months in the tomuzotuximab group and 6.2 months (95% CI 5.8-7.3 months) in the cetuximab group (P = 0.86). The median overall survival (OS) estimate was 11.6 months (95% CI 9.5-17.2 months) in the tomuzotuximab group and 13.8 months (95% CI 12.3-16.4 months) in the cetuximab group (P = 0.96). In an exploratory analysis a small subgroup of p16-positive patients had a significantly longer OS compared with p16-negative patients (hazard ratio 1.860, 95% CI 1.09-3.16, P = 0.02).
The glyco-engineered antibody tomuzotuximab failed to demonstrate improved efficacy with a chemotherapeutic backbone in the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma. It remains a so far unanswered question whether such antibody would partner better with different drugs such as checkpoint inhibitors.
•Tomuzotuximab has a potential higher antibody-dependent cell cytotoxicity than other EGFR-directed antibodies.•Comparison of two anti-EGFR antibodies combined with chemotherapy in patients with squamous cell cancer of head and neck.•Efficacy, safety, and tolerability of tomuzotuximab and cetuximab in combination with chemotherapy were similar.
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