Combination of pegylated-liposomal doxorubicin (PLD) and bevacizumab (B) (PLD-B) in sarcoma (SAR)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 20506-20506
Author(s):  
K. M. Skubitz ◽  
P. A. Haddad
Keyword(s):  
Dose Reduction ◽  
Pegylated Liposomal Doxorubicin ◽  
Skin Toxicity ◽  
Symptomatic Improvement ◽  
Vascular Endothelial ◽  
Toxicity Profile ◽  
Median Dose ◽  
Starting Dose ◽  
Endothelial Growth Factor

20506 Background: Vascular endothelial growth factor (VEGF) plays an important role in many tumors including SAR. Because of the known efficacy of PLD in SAR and the presumed importance of VEGF in SAR, we have treated SAR patients with PLD-B. It is possible that the addition of B to PLD might alter the toxicity profile. The toxicities of this combination are not well described. Methods: To better define the toxicity of the combination of PLD-B in SAR, we reviewed our experience with PLD-B in patients treated between 2004 and 2006. Results: We identified 20 patients with SAR treated with PLD-B at our institution. There were 9 men and 11 women, with a median age of 47.5 years (range 23–77). Ten patients initiated therapy with PLD q28 days at a median dose of 45 mg/m2 (range 45–50), and 10 q14 days at a median dose of 21.2 mg/m2 (range 20–25), in combination with B at 5 mg/kg q14 days. A median of 5 cycles was given (range 1–15). Dose delay was required in 3 patients for the second cycle, and dose reduction was required in 9 patients by cycle 3. Of the 10 patients starting with monthly PLD, 7 were changed to q14 day PLD by cycle 4. Mucositis and skin toxicity were the dose limiting toxicities (DLT) in 14/20 patients, and myelosuppression was the DLT in 1/20 patients. Nine patients were felt to have clinical benefit; 3 had a PR and 6 had SD. Notably, 2/4 recurrent Ewing sarcoma patients had symptomatic improvement and at least SD for 10 and 11 months, respectively, with minor toxicity allowing a good quality of life. Conclusions: This report describes the toxicity profile of PLD-B in 20 patients with SAR. The toxicities observed were similar to those seen with PLD alone, however, these toxicities appeared more pronounced with the addition of B. Since VEGF is important for wound healing, the known effects of B on this process may contribute to more skin and mucosal toxicity of PLD at a given dose. Future studies of PLD-B should consider the potential of increased mucosal and skin toxicity. The use of q14 day PLD to allow more control over toxicity is suggested; a maximal starting dose of 20 mg/m2 is reasonable, although dose reduction will be common due to skin or mucosal toxicity. This combination can be given with limited toxicity, and meaningful responses were observed in recurrent sarcomas, including 2/4 Ewing sarcomas. No significant financial relationships to disclose.

Combination of bevacizumab (A) and pegylated-liposomal doxorubicin (PLD) (PLD-A) in sarcoma (SAR)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9556-9556 ◽  
Author(s):  
P. A. Haddad ◽  
K. M. Skubitz
Keyword(s):  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Skin Toxicity ◽  
Vascular Endothelial ◽  
Toxicity Profile ◽  
Median Dose ◽  
Future Studies ◽  
Endothelial Growth Factor ◽  
Dose Delay ◽  
Toxicity Criteria

9556 Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis (AG) in many tumors including SAR. A has demonstrated efficacy in several common solid tumors. Because of the known efficacy of PLD in SAR and the presumed importance of VEGF in SAR, we have treated SAR patients with PLD-A. It is possible that the addition of A to PLD might alter the toxicity profile. To our knowledge, the toxicities of this combination have not been previously described. Methods: To better define the toxicity of the combination of PLD-A in SAR, we reviewed our experience with PLD-A in patients with SAR treated between 2004 and 2005. Results: We identified 12 patients with SAR treated with PLD-A at our institution. There were 5 men and 7 women, with a median age of 43.5 years (range 27–57). Nine patients initiated therapy with PLD on a 28 day interval at a median dose of 45 mg/m2 (range 45–50), and 3 on a 14 day interval at a dose of 22.5 mg/m2, in combination with A at 5 mg/kg every 2 weeks. A median of 3 cycles was given (range 2–9). Standard CALGB response and NIH common toxicity criteria were used. Dose delay was required in 3 patients for the second cycle, and dose reduction was required in 5 patients by cycle 3. Of the 10 patients starting with monthly PLD, 6 were changed to q 2 week PLD by cycle 4. Mucositis and skin toxicity were the dose limiting toxicities (DLT) in 9/12 patients, and myelosuppression was the DLT in 1/12 patients. Conclusions: This report describes the toxicity profile of PLD-A in 12 patients with SAR. The toxicities observed were similar to those seen with PLD alone, however, there was a suggestion that these toxicities may be more pronounced with the addition of A, though this appears to vary among patients. Since VEGF is important for wound healing, the known effects of A on this process may contribute to more skin and mucosal toxicity of PLD at a given dose. Future studies of PLD-A should consider the potential of increased mucosal and skin toxicity, and the use of q2week PLD to allow more control over toxicity is suggested. [Table: see text]

Patterns Of Non-Hematological Adverse Effects In Patients With Chronic Myeloid Leukemia In Chronic Phase (CML-CP) Treated With Ponatinib – Experience At a Single Institution

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4019-4019 ◽  
Author(s):  
Preetesh Jain ◽  
Hagop M. Kantarjian ◽  
Carlos Guillermo Romo ◽  
Alfonso Quintas-Cardama ◽  
Elias Jabbour ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adverse Effects ◽  
Dose Reduction ◽  
Research Funding ◽  
Skin Toxicity ◽  
Qtc Prolongation ◽  
Single Institution ◽  
Dry Skin ◽  
Starting Dose ◽  
Grade 3

Abstract Introduction Ponatinib is a multi-targeted tyrosine kinase inhibitor (TKI) efficacious in pts with refractory CML. Ponatinib inhibits other tyrosine kinases (e.g. RET, FGFR, FLT3) that may lead to off target adverse effects (AE). We report a single-institution experience of frequencies of non-hematological AE among pts on therapy with ponatinib. Methods A total of 90 pts with CML-CP[49 relapsed refractory (RR), 41 frontline] treated at our institution on clinical trials with ponatinib were analyzed. AE were recorded on each pt visit and charts were reviewed for AE and risk factors. Results For RR pts (n=49)the starting dose of ponatinib was 45 mg in 42 (86%) pts. 39 (80%) had dose interruptions, due in 17 (44%) to grade 3 thrombocytopenia and in 22 (56%) to non-hematological AE (elevated pancreatic enzymes 7 pts of whom 5 had pancreatitis; body aches and headache 7; hypertension 7; skin toxicity 5; fatigue 5). 35 pts (71%) had dose reduction to 30 or 15 mg. Hypertension (H.T.) stage 2 (≥160/100 mm Hg) occurred in 15 (31%) pts; only 2 of new onset. Blood pressure was controlled in all with antihypertensives. Other cardiovascular AE included QTc prolongation in 1 pt, atrial fibrillation in 1 pt, acute myocardial infarction in 3, venous thrombosis in 3, arterial thrombosis in 4, transient ischemic attack (TIA) in 1 and Raynaud’s in 1. No pt discontinued ponatinib due to cardiovascular AE’s. Symptomatic pancreatitis developed in 8 pts (16%). Grade 3/4 elevations in serum lipase and amylase occurred in 12 (24%) pts and 2 (4%) pts respectively. Median days to onset of pancreatitis was 24 (range 7-456). 27 pts (55%) developed cutaneous toxicity including xerosis/dry skin in 10 (37%) and grade 3 erythroderma and exfoliation of the skin in 5. Four pts died, none related to ponatinib. 13 pts went off the study: 5 went to SCT, 3 progressed, 1 pt died in CCyR of multiple co-morbidities, 1 pt had progressive melanoma, 1 pt was transferred to another hospital, and 2 for ponatinib-related AE (headache in 1 and headache, fatigue, depression, and abdominal pain in 1). For pts in frontline setting (n=41) the starting dose was 45 mg in all. 29 pts (71%) had dose interruptions due to one or more of the following: grade 3/4 pancreatic enzyme elevation in 16, myelosuppression in 4, and various non-hematological AE in 15 (skin toxicity in 4, fatigue in 2, headache in 1, chest pain in 2, elevated liver enzymes in 2, suspected seizure vs. TIA in 1, grade 3 diarrhea in 1, memory disturbances in 1, and grade 3 hypertension in 1, erectile dysfunction in 1). 24 pts (59%) had dose reduction, from 45 mg to 30 mg in 20 pts and then to 15 mg in 4 pts. H.T. stage 2 occurred in 3 (7%) pts usually among patients with pre-existing H.T. Other cardiovascular AE included grade 2 QTc prolongation in 1 pt, possible TIA vs. possible seizure in 1, and Raynaud’s in 2. Pancreatitis was seen in 12 pts (29%) with grade 1-2 and 6 pts (15%) with grade 3/4. Grade 3/4 lipase/amylase elevations occurred in 16 (39%) and 3 (7%) pts. Median days to the onset of pancreatitis were 6 (4-22). 34 pts (83%) developed skin toxicity with rash (any grade) in 25 pts (61%), xerosis/dry skin in 18 pts (44%) and grade 3 erythroderma and skin exfoliation in 2 (pts may have had ≥1 type of skin AE). 2 pts discontinued therapy, due to severe xerosis in 1 and recurrent gra 4 neutropenia in another. 1 pt developed grade 2 pericarditis possibly related to ponatinib. For all the 90 pts, risk factors for cardiovascular and pancreatic toxicities included 20 (22%) smokers, 2 heavy alcohol consumers, 27 (30%) obese (BMI ≥30 Kg/m2), 30 (33%) with hypertriglyceridemia, 17 (19%) had hypercholesterolemia and 10 pts were receiving lipid lowering therapies. Conclusions Ponatinib is generally well tolerated and AEs can usually be properly managed. AE are more common in RR pts with greater frequency of hypertension, cardiovascular complications, headache, dry mouth and dose interruptions. Most pts are able to continue therapy after dose adjustments. Disclosures: Kantarjian: ARIAD: Research Funding. Cortes:Ariad, Pfizer, Teva: Consultancy; Ariad, BMS, Novartis, Pfizer, Teva: Research Funding.

Quality of life, vascular endothelial growth factor inhibition, and survival outcomes with combination oral metronomic therapy in platinum refractory epithelial ovarian carcinoma: Results from a randomized study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6048-6048
Author(s):  
Aparna Sharma ◽  
Sachin Khurana ◽  
Prabhat Singh Malik ◽  
Mayank Singh ◽  
Sandeep Mathur ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Histopathological Diagnosis ◽  
Vascular Endothelial ◽  
Patient Reported ◽  
Platinum Refractory ◽  
Metronomic Therapy ◽  
Endothelial Growth Factor

6048 Background: Patients with recurrent and refractory epithelial ovarian cancer (EOC) have dismal outcomes. We evaluated a combination of oral metronomic therapy in platinum refractory EOC vis-à-vis angiogenic marker expression and its impact on patient reported outcomes. Methods: Between October 2017 and September 2019, 75 patients were randomized to receive etoposide (VP-16) (50 mg daily for 14 days) cyclophosphamide (50 mg daily for 28 days) (Arm A, n = 38) or etoposide (VP-16) (50 mg daily for 14 days) cyclophosphamide (50 mg daily for 28 days) and pazopanib (400 mg daily 28 days) every 28 days (Arm B, n = 37). Eligibility criteria included histopathological diagnosis of EOC, platinum refractory disease and ECOG performance status 0-2. Primary endpoint was serological progression free survival (PFS) as defined by Rustin criteria. Quality of Life (QoL) (evaluated using the EORTC QLQC30 and OV 28 questionnaires) and serum vascular endothelial growth factor (VEGF) were ascertained at baseline and after 3rd and 6th cycle. Intention to treat analysis was done. Results: Baseline characteristics were well matched in 2 arms. At a median follow up 14.4 months (95% CI 13.2-15.7), the median serological PFS is better for patients in Arm B 5.1 months (95%CI 3.13-10.33) compared to 3.4 months (95%CI 3-6.53) in arm A ( P= 0.045). Median overall survival (OS) is not reached in arm B versus 11.2 months (95%CI 5.66-NR) in arm A (P= 0.032). Disease progression was seen in 42.1% (n = 16) in Arm A versus 40.5 %(n = 15) in arm B ( P= 0.40). Sixteen patients are maintaining response. Mucositis (29.7% n = 11) and fatigue (13.5%, n = 5) were more in the pazopanib-containing arm ( P= 0.36). Serum VEGF demonstrated significant decline with subsequent cycles of therapy {median values (range): Arm A, baseline; 466.0 pg/mL(123.9-1930) vs. 6 cycles; 92.05pg/ mL(42.34-279.5) P< 0.0001; Arm B, baseline; 382.0 pg/mL(49.44-2054.0) vs 6 cycles; 119.7 pg/mL(18.20-367.5) P= 0.013} without any difference between the two arms ( P= 0.18). QoL symptom scales in both QLQC 30 and OV 28 questionnaires indicated small but significant improvement in pazopanib arm ( P= 0.02) without differences in global (p = 0.96) and physical functioning scales. ( P= 0.68). Conclusions: Addition of pazopanib to etoposide and cyclophosphamide resulted in improvement in serological PFS and OS with a well-tolerated toxicity profile and modest improvement in QoL.Serum VEGF expression requires validation in a larger cohort. Clinical trial information: CTRI/2017/10/010219.

Safety Profile of Trabectedin in Combination With Liposomal Pegylated Doxorrubicin in Relapsed Ovarian Carcinoma: Considerations for Optimal Management

2011 ◽  
Vol 21 (Supp 1) ◽  
pp. S6-S8 ◽  
Author(s):  
Antonio González Martín
Keyword(s):  
Safety Profile ◽  
Older Patients ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Optimal Management ◽  
Toxicity Profile ◽  
Hand Foot Syndrome ◽  
Clinical Consequences ◽  
Health Status Score

The toxicity profile of trabectedin in the OVA-301 trial, that combined trabectedin with pegylated liposomal doxorubicin for the treatment of patients with ovarian cancer, has shown to be predictable and manageable. No unexpected toxicities were found, with neutropenia and transient increase in transaminases as the most common adverse events reported. The elevation in transaminases appeared early and generally decreased in incidence and intensity over subsequent cycles, with no major clinical consequences. A similar safety profile was seen in the analysis of the older patients in the trial. There were no detrimental effects in quality of life with the combination. Moreover, the Global Health Status score was better for the combination arm in those patients with a PFI of 6 to 12 months that were in response after 5 cycles. Trabectedin with pegylated liposomal doxorubicin is not associated with cumulative end-organ toxicities (renal, cardiac, or neurological toxicities). The toxicity profile is different from other second-line strategies without the presence of inconvenient side effects, such as alopecia, hypersensitivity reactions, hand-foot syndrome, or mucositis.

scholarly journals Multidisciplinary Management of Advanced Kidney Cancer

2020 ◽  
Vol 18 (7.5) ◽  
pp. 977-981
Author(s):  
Chad A. LaGrange ◽  
M. Dror Michaelson ◽  
Colleen H. Tetzlaff
Keyword(s):  
Kidney Cancer ◽  
Survival Rates ◽  
Vascular Endothelial ◽  
Multidisciplinary Management ◽  
Close Attention ◽  
Therapy Options ◽  
Endothelial Growth Factor ◽  
Choice Of Therapy ◽  
Overall Survival Rates

A number of therapeutic options are available for the treatment of advanced kidney cancer, including targeted therapy, immunotherapy, and nephrectomy. Choice of therapy for advanced kidney cancer is guided by risk stratification. Immunotherapy combinations are generally superior to vascular endothelial growth factor -based monotherapy, and overall survival rates continue to increase substantially. With new systemic therapy options, additional improvements have been noted in durable responses to treatment and in quality of life. Nephrectomy remains an important consideration in selected patients, particularly those with minimal burden of metastatic disease. Managing the adverse events of treatment of advanced kidney cancer requires close attention and multidisciplinary collaboration.

Antiangiogenic Therapy for Glioblastoma: The Challenge of Translating Response Rate into Efficacy

2013 ◽  
pp. e71-e78
Author(s):  
John de Groot ◽  
David A. Reardon ◽  
Tracy T. Batchelor
Keyword(s):  
Antiangiogenic Therapy ◽  
Response Rates ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial ◽  
Radiographic Response ◽  
Vascular Proliferation ◽  
Neurologic Function ◽  
Endothelial Growth Factor

Glioblastoma are one of the mostly vascularized tumors and are histologically characterized by abundant endothelial cell proliferation. Vascular endothelial growth factor (VEGF) is responsible for a degree of vascular proliferation and vessel permeability leading to symptomatic cerebral edema. Initial excitement generated from the impressive radiographic response rates has waned due to concerns of limited long-term efficacy and the promotion of a treatment-resistant phenotype. Reasons for the discrepancy between high radiographic response rates and lack of survival benefit have led to a focus on identifying potential mechanisms of resistance to antiangiogenic therapy. However, equally important is the need to focus on identification of basic mechanisms of action of this class of drugs, determining the optimal biologic dose for each agent and identify the effect of antiangiogenic therapy on oxygen and drug delivery to tumor to optimize drug combinations. Finally, alternatives to overall survival (OS) need to be pursued using the application of validated parameters to reliably assess neurologic function and quality of life.

scholarly journals Sorafenib for treating head and neck adenocarcinoma of unknown primary site: a case report

2020 ◽  
Vol 48 (11) ◽  
pp. 030006052096435 ◽  
Author(s):  
Jingxian Chen ◽  
Chien-shan Cheng ◽  
Jie Chen ◽  
Lingling Lv ◽  
Xiaoheng Shen ◽  
...  
Keyword(s):  
Head And Neck ◽  
Kinase Inhibitor ◽  
Primary Site ◽  
Unknown Primary ◽  
Vascular Endothelial ◽  
Unknown Primary Site ◽  
Multiple Cycles ◽  
Endothelial Growth Factor ◽  
Generation Sequencing

The aim of the present study was to report a rare case of head and neck adenocarcinoma with an unknown primary site in a 59-year-old man. After disease progression followed by multiple cycles of chemotherapy and radiotherapy, genetic screening using next-generation sequencing identified vascular endothelial growth factor A amplification and the TP53 R209Kfs mutation. Treatment with the multi-targeted protein kinase inhibitor sorafenib controlled the patient’s symptoms and improved his quality of life.

scholarly journals Vascular Endothelial Growth Factor Biology and Its Potential as a Therapeutic Target in Rheumatic Diseases

2021 ◽  
Vol 22 (10) ◽  
pp. 5387
Author(s):  
Thi Hong Van Le ◽  
Sang-Mo Kwon
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Rheumatic Diseases ◽  
Treat To Target ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Physiological Processes ◽  
Life Threatening ◽  
Endothelial Growth Factor

Rheumatic diseases constitute a diversified group of diseases distinguished by arthritis and often involve other organs. The affected individual has low quality of life, productivity even life-threatening in some severe conditions. Moreover, they impose significant economic and social burdens. In recent years, the patient outcome has been improved significantly due to clearer comprehension of the pathology of rheumatic diseases and the effectiveness of “treat to target” therapies. However, the high cost and the adverse effects are the concerns and full remissions are not often observed. One of the main processes that contributes to the pathogenesis of rheumatic diseases is angiogenesis. Vascular endothelial growth factor (VEGF), a central mediator that regulates angiogenesis, has different isoforms and functions in various physiological processes. Increasing evidence suggests an association between the VEGF system and rheumatic diseases. Anti-VEGF and VEGF receptor (VEGFR) therapies have been used to treat several cancers and eye diseases. This review summarizes the current understanding of VEGF biology and its role in the context of rheumatic diseases, the contribution of VEGF bioavailability in the pathogenesis of rheumatic diseases, and the potential implications of therapeutic approaches targeting VEGF for these diseases.

scholarly journals Ocular Complications of Intravitreal Avastin: a Report from Tobruk Medi-cal Center

2020 ◽  
Vol 35 (2) ◽  
pp. 85-93
Author(s):  
Fathy A. Abdolmejed ◽  
Ghamela S. Ali
Keyword(s):  
Intravitreal Injection ◽  
Medical Center ◽  
Sudden Increase ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Causative Microorganism ◽  
Pars Plana ◽  
Endothelial Growth Factor ◽  
Systemic Antibiotics

A retrospective statistical study was done at the ophthalmology department of Tobruk Medical Center on all the patients who received intravitreal medication with Avastin (anti-VEGF (anti-vascular endothelial growth factor)) in the period between August 1st and December 31st, 2018. It is aimed to report the complications of the intravitreal injection (IVI) and how they were managed. Out of the 56 recorded patients, there were 32 (51.9 %) females, all the patients received multiple intravitreal injections, with a total number of 131 injections. The average age of the patients was 56.5 years (ranged from 40-70 years). The most common complications after intravitreal injection were subconjunctival hemorrhage (19%), discomfort/pain (13.7%), blurring of vision (6 %), leaking at injection site (4.6%), floaters (3%), and increase intraocular pressure (IOP) in (13.7%). Six cases out of the eighteen that had high IOP received Diamox (Acetazolamide) Tab. 250 mg one-two hours before the time of injection which did not prevent the post-injection spike of IOP and that was statistically not significant (P=0.09). Thirteen eyes (10 %) developed sudden loss of vision due to sudden increase in IOP immediately after the injection, and all the cases of the high IOP were managed by anterior chamber paracentesis and the vision also improved. Endophthalmitis was recorded in only one case (0.8%), at the third-day post intraocular Avastin injection, the causative microorganism was unknown and treated with intravitreal antibiotics (vancomycin) along with topical and systemic antibiotics and steroids, but the patient did not recover until pars plana vitrectomy was done to him, and the patient recovered his preoperative vision. The patients who had glaucoma or rubeosis iridis suffered significantly (P = 0.01) from an increase in IOP levels (digitally measured) after injection with Avastin, while most other patients who didn't have both pathologies did not suffer from an increase in IOP. It can be concluded that despite having a dramatic effect on the quality of life by improving the central vision, Anti-VEGF can cause serious complications that could be prevented by early diagnosis and treatment

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