The goal of this supportive care study is to learn if high-dose Vitamin E and CoQ10 in combination can reduce the negative sub-acute and chronic side effects of radiation to the pelvis in adults treated for prostate, uterine, cervical, or anal cancer.

The main questions it aims to answer are:

• Is taking high doses of Vitamin E (dl-α-tocopherol acetate, 900mg) and CoQ10 (ubidecarenone, 200 mg) each day safe and tolerable?
• Does a 90-day course of vitamin supplementation with high-dose Vitamin E and CoQ10 reduce the incidence and severity of late radiation-associated toxicities?
• Does high-dose vitamin supplementation with Vitamin E and CoQ10 improve patient reported measure of quality of life?
• Does high-dose vitamin supplementation with Vitamin E and CoQ10 change the trajectory of recovery after radiation therapy?
• Is there evidence that suggests high-dose vitamin supplementation with Vitamin E and CoQ10 impairs oncologic outcomes?
• Can longitudinal biomarkers of oxidative stress be correlated with Vitamin E and CoQ10 concentrations or radiation-associated toxicity?
• Will subjects adhere to the vitamin administration schedule?
• Are there demographic differences in systemic exposure to the vitamins?
• Are there differences in toxicity outcomes across tumor types or radiation dose fractionation schemes?

Participants will be asked to:

• Take Vitamin E and CoQ10 every day for 90 days by mouth.
• Fill out quality of life questionnaires to assess treatment impacts.
• Come for clinic visits every 2-4 weeks for around 4 months, then every 3-6 months for around 2 years.
• Have blood draws more frequently than standard-of-care for clinical laboratory examinations and the collection of research samples.
• Undergo Computed Tomography (CT) imaging of the chest, abdomen, and pelvis more frequently than standard of care.
• Agree to lifestyle changes that ensure adequate vitamin absorption including intermittent abstinence from alcoholic beverages.

The purpose of this study is to determine if high-dose supplementation with the antioxidants Coenzyme Q10 (ubidecarenone) and Vitamin E (dl-α-tocopherol) reduces subacute and chronic radiation-associated toxicity after radiation therapy for pelvic cancers including post-prostatectomy prostate, endometrial, cervical, and anal malignancies. Changes to oncologic outcomes will be assessed to characterize the effects of the vitamin regimen. The safety and tolerability of the vitamin regimen will be tested to determine the recommended phase II dose. Subsequently, the regimen's efficacy towards reducing the incidence and severity of post-treatment toxicity burden will be compared to historical norms. Other objectives of the research include characterizing the trajectory of recovery, patient reported quality of life outcomes, adherence to therapy, and longitudinal changes in biomarkers of oxidative stress.

Exposure to radiation can cause sustained oxidative stress, mitochondrial dysfunction, chronic inflammation, membrane injury, maladaptive tissue remodeling, and ferroptosis. The biological drivers of these effects may be counteracted by increasing the pool of active vitamin E (oxidized α-tocopherol) in affected tissues through perfusion and regeneration by CoQ10 (ubidecarenone as ubiquinol). The subject population will include adults with ECOG performance status ≤2 scheduled for curative-intent external beam radiation therapy ± chemotherapy as treatment for the pelvic malignancies listed above. Participants must be able to swallow gel capsules. Known comorbidities that affect vitamin absorption or tolerability, increase bleeding risk, and/or increase the risk of vitamin E overdose may exclude participation. Prior to the initiation of vitamin therapy, participants must complete at least 80% of their scheduled radiation dose and have adequate hematological, organ and clotting function. Pregnancy, lactation, and refusal of contraceptive precautions (unless exempt) preclude participation.

Research interventions include daily co-administration of vitamin E (450-900 mg) and CoQ10 (100-200 mg) for 90 days immediately following radiation therapy, frequent clinic visits and phlebotomy, PRO questionnaires, and the collection of blood-based research specimens. The duration of participation will vary with the length of radiation therapy but will always involve a 3-month treatment period followed by 21 months of follow up.

Inclusion Criteria:

1. Pathologically confirmed post-prostatectomy prostate, uterine (endometrial and cervical), or anal cancer.

2. Scheduled for curative-intent, multi-fraction (at least 15 fractions) external-beam radiotherapy +/- chemotherapy at the study site which does not involve re-irradiation to the same field.

3. Age ≥ 19 years at the time of consent.

4. Eastern Cooperative Oncology Group Performance Status ≤ 2.

5. Life expectancy ≥ 6 months at the time of consent as determined by the participant's treating physician.

6. Participants must be able to swallow soft-gel capsules.

7. Participants must not have a disease significantly affecting drug absorption (e.g., resection of the stomach or small bowel, symptomatic inflammatory bowel disease, partial or complete bowel obstruction).

8. Participants must agree to limit alcohol consumption to ≤ 2 standard drinks (14 g of pure ethanol) within 6 hours before and 6 hours after vitamin administration.

9. Participants must agree to discontinue current vitamin/mineral supplements, including multivitamins, that contain Vitamin E (α-tocopherol) or CoQ10 (ubidecarenone) and abstain from taking these supplements while on study, including during the follow-up period. Participants must also agree to discontinue and abstain from high-dose vitamin/mineral supplementation while on-study and during the study follow-up period. NOTE: Participants for whom high-dose vitamin/mineral supplementation is medically necessary are eligible if the principal investigator determines that continuing treatment will not impact safety or study outcomes.

10. Women of childbearing potential and male participants with partners of childbearing potential must agree to use two forms of medically effective contraception (at least one of which must be a barrier method) while on study until one month following the last dose of vitamin supplements.

11. As determined by the enrolling physician, the participant must be able to understand and comply with study procedures for the entire length of the study. There must not be psychological, familial, sociological, or geographical conditions potentially hampering protocol compliance, including alcohol dependence or drug abuse.

12. The participant or the participant's legally authorized representative must provide documented informed consent after being informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.

13. Participant must have adequate hematological, organ, and clotting function as defined below. Screening labs must be obtained prior to the end of radiation therapy.

    • Absolute Neutrophil Count (ANC) ≥ 500/mm3
    • Platelets ≥ 50,000/mm3 • Hemoglobin ≥ 8.0 g/dL. The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable.
    • Calculated creatinine clearance (CrCl (mL/min); Cockcroft-Gault formula) ≥ 30 mL/min.
    • Total bilirubin ≤ 1.5X institutional upper limit of normal (ULN) or ≤3 X ULN for patients with known Gilbert's syndrome
    • AST (SGOT) and ALT (SGPT) ≤ 3X institutional ULN
    • PT/INR and PTT (in the absence of lupus anticoagulant) ≤ 2X institutional ULN.

Exclusion Criteria:

1. Participants who do not receive ≥ 80% of the planned total radiation.

2. Participants who are scheduled to receive SBRT/SRS

3. Participant's treatment plan must not include anti-cancer pharmaceutical therapies during the period of vitamin administration (~3 months after completion of radiation therapy).

4. Participants must not receive any other investigational agents while on study.

5. Participants must not have contraindications to Vitamin E or CoQ10 supplementation, including:

   1. Anticoagulation or antiplatelet therapy that cannot be stopped. NOTE: To be eligible, participants must be able to discontinue contraindicated medications at least 2 weeks prior to the initiation of study treatment. These medications may be resumed 1 month after completing study treatment.
   2. Underlying bleeding conditions (e.g., hemophilia or von Willebrand disease)
   3. Retinitis pigmentosa
   4. Hepatobiliary dysfunction
   5. Vitamin K deficiency
   6. Preexisting severe fibrosis
   7. History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage.
   8. Uncontrolled Grade 2 hypertension defined as ≥ 140 mm Hg systolic blood pressure or ≥ 90 mm Hg diastolic blood pressure.
   9. Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenia purpura).
   10. Uncontrolled systemic bacterial, fungal, parasitic, mycobacterial, viral, or other infections, despite appropriate antibiotics or other treatments.
   11. Any other uncontrolled comorbidities that, in the opinion of the treating investigator, would compromise subject safety or study outcomes.

6. Participant must not have a history of allergic reactions to Vitamin E or CoQ10 or any of the vitamin excipients (soybean oil, soy lecithin, gelatin, glycerin).

7. Not pregnant or lactating. A negative pregnancy test (serum hCG) is required for participants of childbearing potential. Female participants who are permanently sterilized (hysterectomy/bilateral oophorectomy) or postmenopausal (12 months of consecutive amenorrhea, > 45 years-of-age in the absence of other biological or physiological causes; females < 55 years-of-age with serum FSH level > 40 mIU/mL) are exempt