Patient demographics

Tocopheryl polyethylene glycol succinate docetaxel prescription

The dose of TPGS docetaxel ranged from 20 mg/m2 to 120 mg/m2, with a most commonly prescribed dose of 75 mg/m2 for head and neck squamous cell carcinoma, hormone-resistant prostate cancer and gastric cancers. In breast cancer patients, in addition to the 75 mg/m2 dosage, the treating clinicians also employed a 60 mg/m2 dosage. Patients completed an average of 4.25 cycles of chemotherapy and each infusion with 100 ml of normal saline took 30 min.

Efficacy results

In the study, while 25 (40.98%) patients had a partial response, 17 (27.86%) patients had stable disease. Five (8.19%) patients progressed and 4 (6.55%) patients died during the chemotherapy [Table 2], which was adjudicated to be unrelated to the drug, as opined by the treating clinician.

Efficacy of tocopheryl polyethylene glycol succinate - docetaxel in various cancers

Safety evaluation

AE were reported in 42 patients in the safety data set. All AEs are listed in [Table 3]. There were no AEs pertaining to hypersensitivity reported during the study. One AE of Grade 3 hand foot syndrome was encountered.

Summary of adverse events (n=42)

Discussion

Docetaxel is approved as the first-line treatment option for advanced or metastatic breast, head and neck squamous cell carcinoma and non-small cell lung cancer. Apart from the cancers mentioned above, docetaxel is also used in the treatment of numerous other malignancies.[6] In general, patients in real-world settings tend to fare better than patients who are tested in controlled settings.[19] Although in our study, we have not presented the bifurcated results based on cancer types, the overall results suggest that 42 (77%) patients had a stable or partial response with TPGS-docetaxel. These results are agreeable with earlier studies, where patients on docetaxel had a response rate of 53%–82%.[20] Expectedly, in the Phase III trial, when docetaxel was used as a single agent, the response rate was much lower between 30%-and 42%.[20],[21]

The most common AEs reported in our study was fatigue (47.6%), followed by neurosensory symptoms (23.8%), pedal edema (23.8%), neutropenia (7.1%), hand-and-foot syndrome (4.7%), pleural effusion (2.3%) and mucositis (2.3%). It has to be emphasized that there were no hypersensitivity or anaphylactic reactions reported in this study. In terms of safety, the findings from a comprehensive drug review of docetaxel conducted by Figgitt and Wiseman[20] reveals that hypersensitivity reactions were reported in 31.3%-patients, which was nil in this study owing to the nonimmunogenic property of the novel formulation. Further, hematological toxicities were reported in >90%-patients receiving 100 mg/m2 dose. However, in this study, since most of the patients received a lower dose of 75 mg/m2, the incidence of hematological AEs was understandably lower at 7%. Similarly, dermatological toxicities (64.3%) fluid retention (46.7%) and neurosensory AEs (47.9%) were higher in the previous reports compared to our study.

Collectively, the efficacy of the novel TPGS docetaxel formulation is consistent with previous literature, implying a robust outcome benefit. Importantly, in line with our hypothesis, TPGS-docetaxel was associated with decreased rate of hypersensitivity reaction compared to polysorbate 80 containing formulation. The mechanism responsible for this reduced hypersensitivity can be attributed to (1) PEG component being less immunogenic, (2) distinct property of the tocopheryl (Vitamin E) component, which inhibits immune-mediators such as IgE, leukotrienes and histamines.[22],[23],[24]

Although our study captured the clinical outcomes in terms of efficacy and safety, it was not without any limitation by virtue of its design. First, one could not capture progression-free or overall survival in these patients. Since, the data were retrieved from the medical records; the patient follow-up was limited till the subsequent visit to the hospital and not always till progression or death. Second, the overall data collection period was intended to capture the AEs and efficacy only on short-term basis. Third, by the very nature of the retrospective design, there is an inherent flaw of missing data for the analysis. Finally, there was no uniformity in dosing strength and frequency, and indications for prescribing, as every hospital followed their own protocol.

Conclusion

Although large data set of patients, who have been dosed uniformly with TPGS-docetaxel would be necessary to draw robust inference, preliminary evidence suggests that the novel TPGS-based docetaxel formulation is efficacious in various cancers, and importantly, it has an enhanced safety profile, as it is devoid of polysorbate 80 induced hypersensitivity reactions.

Conflict of Interest

There are no conflicts of interest.

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Address for correspondence

Publication History

Received: 21 October 2019

Accepted: 01 June 2020

Article published online:
17 May 2021

© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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