Evaluating the effectiveness of melatonin for the prevention of taxane-induced peripheral neuropathy in patients with breast cancer: A double-blinded randomized clinical trial

Evaluating the efficacy of melatonin for the prevention of taxane-induced peripheral neuropathy

In this phase 3 randomized double-blinded controlled clinical trial, 132 patients with breast cancer who are candidates for chemotherapy with taxanes will be divided into intervention (n = 66) and placebo (n = 66) groups based on a random number table.

Patients in melatonin group will receive 15 mg of melatonin daily from the first day of receiving docetaxel for 12 weeks. Likewise, patients in the control group will receive a placebo daily for 12 weeks. At baseline, patients will be assessed in terms of neuropathy via The Michigan Neuropathy Screening Instrument (MNSI), DN4 questionnaire, neurofilaments, and Diapazone test. Demographic characteristics, taxane-induced adverse effects, sleep quality, anxiety, and other medications will be recorded for each patient. Patients will be reassessed for neuropathy at the end of their chemotherapy and 3 months after chemotherapy termination. The study will be carried out in Shahid Ghazi hospital, Tabriz.

Inclusion criteria: Patients of age 18-85 years with breast cancer who are candidates for chemotherapy with taxanes; exclusion criteria: history of neuropathy, use of medications that can cause neuropathy, history of allergy to melatonin, alcohol intake, active infection, history of prior chemotherapy, severe kidney or liver disease

Patients in the first group (experimental group) will receive melatonin. The second group will be considered a placebo group and patients will receive a placebo.

Frequency of taxane-induced peripheral neuropathy

I respectfully request an amendment to the start and end dates of the patient enrollment period for our registered trial. The initially recorded dates in the primary registration were estimated based on the research team's preliminary planning. However, following the finalization of study documentation and reports, the exact start and end dates have now been determined based on valid supporting documents, including the Ethics Committee approval letter and the dates of the first and last patient visits. Since the actual dates of the study differ from those previously entered in the system, and given that accurate timeline reporting is essential for the scientific validity of the study—particularly for international journals (otherwise, the study may be considered retrospective and face rejection during the peer-review process)—I kindly request that the system be updated with the correct dates, as supported by the attached documentation. I would be grateful for your guidance and consideration. Should any further documents or clarifications be required, I am ready to provide them promptly.

132 patients with breast cancer who are candidates for chemotherapy with taxanes and referred to the clinic or hospital ward of Shahid Ghazi Hospital will be divided into two groups (intervention and control) after screening based on inclusion and exclusion criteria. A simple randomization procedure will be performed based on a table of random numbers.

Patients with breast cancer who are qualified to participate in the study based on the inclusion and exclusion criteria will enter the study after signing informed consent. Participants will not be aware of the type of drug (either melatonin or placebo). Also, researcher and physicians who refer the patients to the researcher will not be informed about the type of drug (either melatonin or placebo). Only the monitoring committee of the clinical study is informed.