Treatment with nanosomal paclitaxel lipid suspension versus conventional paclitaxel in metastatic breast cancer patients - a multicenter, randomized, comparative, phase II/III clinical study.

Background: A novel nanosomal paclitaxel lipid suspension (NPLS), free from Cremophor EL (CrEL) and ethanol, was developed to address the solvent-related toxicities associated with conventional paclitaxel formulation. Objective: To evaluate the efficacy and safety of NPLS versus CrEL-based paclitaxel (conventional paclitaxel) in patients with metastatic breast cancer (MBC). Design: A prospective, open-label, randomized, multiple-dose, parallel, phase II/III study. Methods: Adult (18-65 years) female patients with MBC who had previously failed at least one line of chemotherapy were randomized (2:2:1) to NPLS 175 mg/m2 every 3 weeks (Q3W, n = 48, arm A), NPLS 80 mg/m2 every week (QW, n = 45, arm B) without premedication or conventional paclitaxel (Taxol®, manufactured by Bristol-Myers Squibb, Princeton, NJ, USA) 175 mg/m2 Q3W (n = 27, arm C) with premedication. In the extension study, an additional 54 patients were randomized (2:1) to arm A (n = 37) or arm C (n = 17). Results: Pooled data from the primary study and its extension phase included 174 patients. The primary endpoint was the overall response rate (ORR). As per intent-to-treat analysis, ORR was significantly better in the NPLS QW arm as compared to conventional paclitaxel [44.4% (20/45) versus 22.7% (10/44), (p = 0.04)]. An improvement in ORR with NPLS Q3W versus conventional paclitaxel arm [29.4% (25/85) versus 22.7% (10/44)] (p = 0.53) was observed. Disease control rates observed were improved with NPLS Q3W versus conventional paclitaxel Q3W (77.7% versus 72.7%, p = 0.66) and with NPLS QW versus conventional paclitaxel Q3W (84.4% versus 72.7%, p = 0.20), although not significant. A lower incidence of grade III/IV peripheral sensory neuropathy, vomiting, and dyspnea was reported with NPLS Q3W versus conventional paclitaxel Q3W arms. Conclusion: NPLS demonstrated an improved tumor response rate and a favorable safety profile versus conventional paclitaxel. NPLS 80 mg/m2 QW demonstrated a significantly better response versus conventional paclitaxel 175 mg/m2 Q3W. Trial registration: Clinical Trial Registry-India (CTRI), CTRI/2010/091/001344 Registered on: 18 October 2010 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjEzNQ==&Enc=&userName=CTRI/2010/091/001344), CTRI/2015/07/006062 Registered on: 31 July 2015 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTE2Mjc=&Enc=&userName=CTRI/2015/07/006062).

Role of nanosomal paclitaxel lipid suspension (NPLS) in the treatment of patients with metastatic breast cancer (MBC) Why was the study done? Paclitaxel is a commonly used drug for the treatment of breast cancer. Conventional formulation of paclitaxel is known to cause side effects like injection site reactions. A newer formulation named NPLS was developed to overcome the limitations of the conventional paclitaxel. The current study was done to compare the safety and effectiveness of NPLS and conventional paclitaxel in patients with advanced breast cancer. What did the researchers do? The research team conducted a large study in multiple hospitals across India, involving women with advanced breast cancer who had experienced treatment failure with previous chemotherapy. A total of 174 patients were randomly assigned to receive either of the three treatment schedules: (1) NPLS every 3 weeks, (2) NPLS every week, (3) conventional paclitaxel every 3 weeks. What did the researchers find? The results showed that NPLS, in a weekly schedule, led to better tumor response rates compared to conventional paclitaxel given every 3 weeks. Additionally, NPLS demonstrated a favorable safety profile, as compared to conventional paclitaxel. What do the findings mean? These findings suggest that NPLS could be a promising alternative for women with advanced breast cancer. NPLS improved the response to treatment, with a better safety profile compared to conventional paclitaxel.

Interfraction variations in doses at OARs during three-dimensional high dose rate brachytherapy planning of cervix cancer.

Objective: The American Brachytherapy (BT) Society recommends that BT must be included as a component of the definitive radiation therapy for cervical carcinoma because recurrences and complications are decreased when BT is used in addition to external beam radiotherapy. The aim of this study is to quantify the interfraction dose variations (VARacts) during high dose rate (HDR) BT, the effect of variation in dose in terms of excess "unrecognized" dose to OAR and to conclude the reason of the variation in reference of applicator position/geometry versus deformation of the organ at risk (OAR) concerned. Materials and Methods: Total 30 patients of carcinoma cervix, biopsy proven, between June 2018 and May 2019, were taken for the study. All patients were treated with external beam radiation therapy to a dose of 50 Gy in 25 fractions over 5 weeks, followed by three fractions of HDR intracavitary brachytherapy (ICBT) (7.5 Gy to point A in each fraction) by two-dimensional (2D) X-ray-based planning. Before treatment in the first and last fraction of BT, computed tomography (CT) scan was done for every patient. Then, a 3D-based planning was performed with CT images on our HDR Plus software with image sequence option. VARact was calculated. Rigid image registration of consecutive fraction images was used for quantification of the hypothetical variation in dose (VARhypo) arising exclusively due to changes in applicator placement and geometry. Results: The mean contoured rectal volumes for the first and third fractions were 41.49 cc and 44.72 cc, respectively, while the respective volumes for bladder were 9.33 cc and 9.35 cc cm. These differences were statistically insignificant (P value: 0.263 and 0.919 for rectum and bladder, respectively). The mean equivalent dose in 2 Gy fraction (EQD2) bladder D2cc was 5.68 Gy and 5.79 Gy in the first and third fraction ICBT, respectively. The mean EQD2 for the rectal D2cc was 11.63 Gy and 12.85 Gy in the first and third fraction ICBT, respectively. None of the patients had an actual cumulative EQD2 more than 90 Gy for bladder, but 36.66% of the patients had a rectal dose exceeding the tolerance (75 Gy). Regression plots showed that VARhypo alone could predict about 42.2% of the VARact in the rectum and 19.2% of the VARact in the bladder. Thus, the remaining variation was due to the organ deformation-related dose variations between the two fractions. Conclusions: There were no statistically significant variations in the volumes or doses of OAR between the two fractions. However, a significant proportion of patients may have a higher dose to the OAR in the third fraction in the absence of individualized planning. This increase is likely to be more detrimental where higher doses per fraction are used. Variations in OAR doses may be caused by organ deformation and/or changes in applicator placement/geometry.

Role of maintenance paclitaxel in epithelial ovarian cancer: An affordable option for poor resources countries (a Regional Cancer Institute study).

Purpose: The purpose of the study is to assess the benefits of maintenance chemotherapy (CT) in epithelial ovarian cancer with CT and surgery. The primary and secondary endpoints of the study were progression-free survival (PFS) and overall survival (OS), respectively. Patients and Methods: Three hundred patients with ovarian cancer (registered between January 2012 and December 2013) received 6 cycles of 3 weekly CT (injection paclitaxel 175 mg/m2 + injection carboplatin 6 AUC) and surgery. After 4 weeks of completion of the above treatment, patients were assessed for response with radiological imaging and serum CA125. Then, these patients were randomly allotted in two arms; 150 patients in Arm A received 6 cycles of single agent, 3 weekly injection paclitaxel 175 mg/m2 as maintenance therapy while 150 patients in Arm B, were on observation. The follow-up was done at 1 month, then 3 monthly in the 1st year and 6 monthly in the 2nd year to evaluate PFS and annually up to 5 years for OS. Results: The PFS at 1 and 2 years was 91% and 80% in study arm and 65% and 50% in control arm; the differences were statistically significant (P = 0.010). The 5-year overall survival was 43% versus 38% in study and control arms, respectively (P = 0.410) and 5-year PFS was 28% versus 18% (P = 0.039) in maintenance and observation arm, respectively. Except for peripheral neuropathy, there was no statistically significant difference in toxicities between the two arms. Conclusion: The study suggests that 6 cycles of single-agent paclitaxel maintenance therapy significantly prolongs the duration of PFS and better trends toward OS, though a large study is needed to come to a conclusion.

Chart Review Presenting Safety of Injectable PLLA Used With Alternative Reconstitution Volume for Facial Treatments.

BACKGROUND: Since the approval of Sculptra Aesthetic, the amount of sterile water used to reconstitute the product has gradually increased in clinical practice. A retrospective chart review was conducted to evaluate patient safety associated with a larger reconstitution volume, and to investigate specific parameters for how Sculptra Aesthetic is used in a real-world clinical setting. OBJECTIVE: The primary objective of the study was to evaluate the safety of Sculptra Aesthetic when using a reconstitution volume of 7 to 10 mL, via collection of adverse events related to the product or injection procedure reported in medical records. METHODS: This was a multi-center, retrospective chart review conducted in the US. Medical records for subjects treated in the facial area with Sculptra Aesthetic reconstituted to 7–10 mL were reviewed to obtain information about demographics, treatment data, and adverse events. Each injector completed a questionnaire regarding reconstitution and injection procedures generally used. RESULTS: There were 4483 treatments performed in 1002 subjects; nearly half (48%) had 3 or 4 treatments during the studied period. Subjects most commonly received treatment in the midface/cheek area (97%), temple (94%), and jawline (54%). All injectors indicated adding lidocaine to the solution, resulting in total volumes of 8–10 mL. Adverse events were reported by 3.6% of subjects, all mild in intensity. Nodules were reported by 4 subjects (0.4%). CONCLUSION: The low number of AEs reported in this retrospective chart review suggests that facial aesthetic treatment with PLLA reconstituted to a final volume of 8–10 mL, including anesthetics, is associated with a favorable risk benefit ratio. J Drugs Dermatol. 2021;20(1):18-22. doi:10.36849/JDD.5631.