An open-label study to evaluate dose and cycle dependence of the pharmacokinetics (PK) of pegylated liposomal doxorubicin (PLD)

2012 Background: There are no definitive data in humans on the dose dependency and/or cycle dependency of the pharmacokinetics of PLD. The skin toxicity of PLD tends to worsen after several treatment cycles. Therefore, it is important to characterize the PK of PLD after 2 or more cycles. Methods: Fifteen patients with various solid tumors were randomized to two arms of treatment in an open-label study. Arm A received PLD at doses of 60, 30, and 45 mg/m2 in 3 successive cycles every 4 weeks (q4w). Arm B received PLD at doses of 30, 60, and 45 mg/m2 in 3 successive cycles q4w. Twelve patients, 6 on each arm, completed all three cycles and were fully evaluable. Plasma levels of doxorubicin were analyzed by HPLC and fluorimetry following a previously published method (J Chromatogr B, 779:259–69, 2002) with minor modifications. PK analysis was done by non-compartmental method. The following parameters were obtained: Cmax, AUC∞, terminal half-life (T1/2), and Clearance (CL). The paired t test was used for statistical analysis. Results: There was no significant difference in the parameters examined when the dose was increased from 30 to 60 mg/m2. However, when we analyzed the effect of cycle number on the PK, we found a gradual and significant inhibition of CL when patients advance from the 1st through the 3rd cycle of PLD (p=0.0003), with a mean increase of 44% in AUC/mg dose (p=0.0011). Cmax and T1/2 mean values increased by 17% and 18% respectively between the 1st and 3rd cycles, but only the increase in T1/2 was statistically significant (p=0.0127). Conclusion: While the PK of PLD is not dose-dependent within the dose range of 30 to 60mg/m2, there is evidence of a cycle-dependent effect that results in inhibition of CL when patients receive successive cycles of PLD. This effect may account for the delayed skin toxicity of PLD. These results suggest the need for dose adjustments of PLD to minimize the risk of toxicity, such as an initial high loading dose followed by reduced maintenance doses from the 2nd or 3rd cycle onwards. [Table: see text] [Table: see text]

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Impact of prior pegylated liposomal doxorubicin (PLD) treatment in recurrent ovarian cancer (ROC): Sub-group analysis from a randomized, open-label study comparing trabectedin (T) and PLD versus PLD alone in ROC (ET743-OVC-3006)

Annals of Oncology ◽

10.1093/annonc/mdz250.038 ◽

2019 ◽

Vol 30 ◽

pp. v420-v421

Author(s):

B.J. Monk ◽

T.J. Herzog ◽

S. Triantos ◽

S. Maul ◽

G. Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Liposomal Doxorubicin ◽

Group Analysis ◽

Pegylated Liposomal Doxorubicin ◽

Recurrent Ovarian Cancer ◽

Open Label ◽

Open Label Study ◽

Label Study

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Rate of complete chemotherapy as planned with comprehensive geriatric assessment guided intervention among vulnerable elderly cancer patients: A randomized-open-label study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e24021 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e24021-e24021

Author(s):

Manupol Maikami ◽

Napa Parinyanitikul ◽

Nattaya Poovorawan

Keyword(s):

Usual Care ◽

Cancer Patients ◽

Comprehensive Geriatric Assessment ◽

Intervention Group ◽

Control Group ◽

Open Label ◽

Elderly Cancer Patients ◽

Open Label Study ◽

Label Study ◽

Significant Difference

e24021 Background: The Geriatric 8 (G8) is a simplified screening tool to select the appropriate elderly patients for chemotherapy. Vulnerable patients with impaired G8 score might need additional comprehensive geriatric assessment (CGA) with intervention for individual problem. However, the impact of CGA and therapeutic intervention on rate of complete chemotherapy among these patients is rarely addressed. This study aims to evaluate the benefit of CGA guided intervention. Methods: A single center, randomized, open-label study which included newly diagnosed elderly cancer patients (age ≥ 65) with impaired G8 score (≤ 14) who were designated for chemotherapy. After the enrollment, patients were randomized to 1:1 ratio to receive CGA guided intervention (intervention group) or usual care (control group). The primary end point was the rate of complete chemotherapy at 90-day. Associated factors for complete chemotherapy were evaluated. Results: Between June 2019 and December 2019, 52 patients were randomized (26 patients for intervention group and 26 patients for control group). Mean age was 72 years, 59.6% was female, 40.4% had breast cancer and 51.9% had early stage cancer. With G8 assessment, 55.8% had intermediate (score 11-14) and 44.2% had low (score < 11) impaired G8 score. All baseline characteristics were balanced. Using per protocol analysis, there was no significant difference in rate of complete chemotherapy between groups (61.9% vs 50%, OR 1.63; 95%Cl 0.51-5.23; p = 0.42). Considering subgroup analysis in the intermediate G8 score patients, the intervention group had a significant higher rate of complete chemotherapy than control group (81.8% vs 66.7%, OR 2.71; p = 0.02), but no significant difference in low G8 score group (40% vs 27.3%, OR 1.78; p = 0.58). In univariate analysis, age below 75 years, BMI > 20 kg/m2 and intermediate G8 score showed significant factors for improving rate of complete chemotherapy. Conclusions: This is the first study in south-east Asia using CGA and intervention to improve rate of completion in chemotherapy. Although the CGA and intervention had no significant difference but had tendency to be better in completion rate of chemotherapy than usual care. The intermediate-impaired G8 score subgroup is more likely to benefit from CGA guided intervention for complete chemotherapy as planned.

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Effect of personalized wrist orthosis for wrist pain with three-dimensional scanning and printing technique: A preliminary, randomized, controlled, open-label study

Prosthetics and Orthotics International ◽

10.1177/0309364618785725 ◽

2018 ◽

Vol 42 (6) ◽

pp. 636-643 ◽

Cited By ~ 5

Author(s):

Sang Jun Kim ◽

Sung Jae Kim ◽

Yong Ho Cha ◽

Keun Ho Lee ◽

Jeong-Yi Kwon

Keyword(s):

Hand Function ◽

Three Dimensional ◽

Wrist Pain ◽

Control Group ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

High Satisfaction ◽

Significant Difference ◽

Experimental Group

Background: Three-dimensional printer technology can produce the personalized orthosis in various forms. Objective: To develop a personalized wrist orthosis using a three-dimensional scanner and three-dimensional printer for patients with wrist pain. Study design: A preliminary, prospective, randomized, open-label study. Methods: A total of 22 patients with wrist pain were randomly assigned to the control and experimental groups. The control group wore a cock-up orthosis and the experimental group wore a three-dimensional-printed wrist orthosis for 1 week. The Patient-Rated Wrist Evaluation, Jebsen Hand Function Test, and Orthotics and Prosthetics Users’ Survey were checked before and 1 week after the application. Results: The Patient-Rated Wrist Evaluation showed significant pain relief in both groups. Two items of the 28 Orthotics and Prosthetics Users’ Survey questions, “Put toothpaste on brush and brush teeth” and “Dial a touch tone phone,” showed high satisfaction scores, with statistically significant difference in the experimental group ( p = 0.036 and 0.004). Conclusion: The three-dimensional-printed wrist orthosis was superior to the cock-up orthosis for two items of the Orthotics and Prosthetics Users’ Survey. Wrist pain was reduced in the group wearing the three-dimensional-printed wrist orthosis as well as the group wearing the cock-up orthosis, so the three-dimensional-printed wrist orthosis could possibly play the same role as the cock-up orthosis. Clinical relevance A three-dimensional-printed wrist orthosis can be a substitute for a conventional ready-made wrist orthosis for patients with wrist pain with more satisfaction.

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