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]

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.

A phase 1b study of chemoimmunotherapy with pegylated liposomal doxorubicin and pembrolizumab in estrogen receptor-positive, endocrine-resistant breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1049-1049
Author(s):  
Alberto A. Gabizon ◽  
Nathan Cherny ◽  
Rut Isacson ◽  
Areen Abu Remilah ◽  
Alberto Gabizon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Liposomal Doxorubicin ◽  
Safety Information ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Skin Toxicity ◽  
Pharmacokinetic Analysis ◽  
Estrogen Receptor Positive ◽  
Phase 1B

1049 Background: This is a single center phase 1b study of a regimen of pembrolizumab (PBZ) and pegylated liposomal doxorubicin (PLD) in endocrine-resistant breast cancer. PLD was chosen as chemotherapy component because it is mildly myelosuppressive and non-immunosuppressive and contains doxorubicin, a strong immunogenic cell death inducer. Methods: Patients with estrogen receptor positive, HER2 negative, metastatic breast cancer, whose disease progressed on hormonal and biological therapy and up to 2 chemotherapy lines were eligible for enrollment. PLD, 30 mg/m2, and PBZ, 200 mg flat dose, were infused on day 1 of every 3-week cycles. The main study objectives were safe dose clearance, characterization of dose-limiting toxicities (DLT), tumor response, and pharmacokinetic analysis of PLD and PBZ during the first 3 cycles of treatment in a 1st cohort of 6 patients and a 2nd confirmatory cohort of 6-9 patients. Patients with partial response (PR) or stable disease (SD) continued on the extended phase of the study consisting of 9 additional cycles during which further safety information was collected. All patients were followed-up for survival. Results: 12 patients were recruited (median age 61 y, range 45-91). 9 patients had received prior doxorubicin treatment. 82 treatments have been administered (median: 7, range 2-13). Overall, treatment was well tolerated. DLT including infusion reactions, grade ≥2 myelosuppression, hair loss and mucocutaneous toxicity were not observed in the first 3 cycles. Subsequently, skin toxicity (grade 2-3 palmar-plantar erythema) was observed forcing treatment delays of 1-2 weeks. Except for 2 cases of subclinical hypothyroidism, there were no other apparent PBZ-related side-effects. There was no evidence of cardiac toxicity. There were 2 early deaths (days 25 and 45) probably related to disease progression. Upon reevaluation on week 9, we observed: 2 patients with PD, 4 with SD, 2 with PR (15+ and 5+ mth), 1 with no measurable disease, and 1 early to evaluate. Three out of 5 patients responded well to post-study chemotherapy with durable improvement or stabilization (range, 5 to 11+ mth). Median follow-up is 14 mth. Median survival has not been reached with 4 deaths and a longest survivor of 19+ mth. Median progression-free survival is 6.0 mth. The clearance of PLD was slow with high Cmax, long T½ and small Vd. There was a significant increase in the AUC of PLD between the 1st and 3rd cycle (median: 2,649 vs 3,422 mg*h/l, p = 0.039). Analysis of PBZ plasma levels is ongoing. Conclusions: The combination of PLD and PBZ is well tolerated and feasible for extended treatment. Dose interval of PLD should be lengthened to 4 weeks after 2-3 cycles to prevent skin toxicity. The late appearance of skin toxicity is probably related to a delay in PLD clearance after 2 treatment cycles with PLD and PBZ. Clinical trial information: NCT03591276 .

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.

Skin toxicity associated with pegylated liposomal doxorubicin (40 mg/m2) in the treatment of gynecologic cancers

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 5080-5080
Author(s):  
R. J. Kim ◽  
G. Peterson ◽  
B. Kulp ◽  
K. M. Zanotti ◽  
M. Markman
Keyword(s):  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Skin Toxicity ◽  
Gynecologic Cancers

Skin toxicity associated with pegylated liposomal doxorubicin (40 mg/m2) in the treatment of gynecologic cancers

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 5080-5080
Author(s):  
R. J. Kim ◽  
G. Peterson ◽  
B. Kulp ◽  
K. M. Zanotti ◽  
M. Markman
Keyword(s):  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Skin Toxicity ◽  
Gynecologic Cancers

scholarly journals P1001RENAL DAMAGE ASSOCIATED WITH INTRAVITREAL ADMINISTRATION OF ANTI-VEGF DRUGS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria Fernandez-Vidal ◽  
Candela Moliz ◽  
Beatriz Redondo ◽  
Teresa Bada Bosch ◽  
Lucia Aubert ◽  
...  
Keyword(s):  
Renal Function ◽  
Diabetic Patients ◽  
Vascular Endothelial ◽  
Median Dose ◽  
Anti Vegf ◽  
Group 2 ◽  
Endothelial Growth Factor ◽  
Group 1

Abstract Background and Aims Vascular endothelial growth factor inhibitors (anti-VEGF) have been shown to be effective in the treatment of macular degeneration and diabetic macular edema. It is known that systemic administration of these drugs can produce adverse renal effects, such as decreased glomerular filtration rate (eFGR), proteinuria, hypertension or thrombotic microangiopathy. However, there is little information about it when the administration is intravitreal. The aim of this study was analyzed the effect of anti-VEGF drugs on renal function and proteinuria. Method Observational and prospective study on diabetic patients, which were divided into two groups: non-cronic kidney disease (CKD) (group 1) and CKD (group 2). We analyzed clinical and analytical variables during follow-up. Results We included 45 diabetic patients (55.6% males) with a median age of 75 (50-91) years. Forty one patients (91.1%) were hypertensive and thirty three (73.3%) were CKD patients. Twenty six (57.8%) received bevazicumab, while the rest (42.2%) received ranibizumab, with a median dose of 6 (1-22). The median follow-up was 25 (9-94) months. The evolution of eFGR and albuminuria are described in Figure 1, where it stands out the increase in albuminuria in group 2. Regarding the drug type, there were no differences. Within the CKD group, one patient presented two episodes of decompensation of heart failure after the administration of an anti-VEGF drug, and two required the initiation of renal replacement therapy. Conclusion Based on the results of our cohort, we believe that it would be advisable to establish a closer monitoring in diabetic patients who are administered an intravitreal anti-VEGF drug, with determination of renal function as well as albuminuria to establish an early diagnosis of possible complications.

scholarly journals Extracorporeal Elimination of Circulating Pegylated Liposomal Doxorubicin (PLD) to Enhance the Benefit of Cytostatic Therapy in Platinum-Resistant Ovarian Cancer Patients

2015 ◽  
Vol 58 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Ondřej Kubeček ◽  
Milan Bláha ◽  
Daniel Diaz-Garcia ◽  
Stanislav Filip
Keyword(s):  
Ovarian Cancer ◽  
Metastatic Disease ◽  
Liposomal Doxorubicin ◽  
Tumor Tissue ◽  
Pegylated Liposomal Doxorubicin ◽  
Skin Toxicity ◽  
Liposomal Form ◽  
Female Population ◽  
Platinum Resistant ◽  
Treatment Tolerance

Ovarian cancer is the fifth most common malignancy in the world’s female population and with the highest lethality index among gynecological tumors. The prognosis of metastatic disease is usually poor, especially in platinum-resistant cases. There are several options for the treatment of metastatic disease resistant to platinum derivates (e.g. paclitaxel, topotecan and pegylated liposomal doxorubicin), all of which are considered equipotent. Pegylated liposomal doxorubicin (PLD) is a liposomal form of the anthracycline antibiotic doxorubicin. It is characterized by more convenient pharmacokinetics and a different toxicity profile. Cardiotoxicity, the major adverse effect of conventional doxorubicin, is reduced in PLD as well as hematotoxicity, alopecia, nausea and vomiting. Skin toxicity and mucositis, however, emerge as serious issues since they represent dose and schedule-limiting toxicities. The pharmacokinetics of PLD (prolonged biological half-life and preferential distribution into tumor tissue) provide new possibilities to address these toxicity issues. The extracorporeal elimination of circulating liposomes after PLD saturation in the tumor tissue represents a novel and potent strategy to diminish drug toxicity. This article intends to review PLD characteristics and the importance of extracorporeal elimination to enhance treatment tolerance and benefits.

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