The relationship of glutathione with ovarian cancer

Introduction

Ovarian cancer remains one of the deadliest forms of cancer among women, with high mortality rates in both the United Kingdom and the United States. Cisplatin (CDDP) is one of the most effective drugs for treating ovarian cancer, but its severe side effects—especially neurotoxicity and nephrotoxicity—limit the number of doses patients can tolerate. This limitation often prevents patients from completing a full treatment cycle of six doses, which is considered optimal for treatment efficacy.

Glutathione (GSH), a naturally occurring antioxidant, has shown potential in earlier small-scale studies for protecting against cisplatin’s toxic effects. This study aimed to evaluate whether GSH could reduce cisplatin-induced toxicity, allowing patients to complete full treatment cycles while maintaining or improving quality of life.

Study Design and Methodology

This double-blind, randomized, placebo-controlled trial involved 151 women with stages I-IV ovarian cancer. Participants were randomly assigned to two groups:

• CDDP group (control group): Received 100 mg/m² cisplatin (n = 77).
• CDDP + GSH group (treatment group): Received 100 mg/m² cisplatin with an additional 3 g/m² intravenous glutathione (n = 74).

Each patient underwent up to six treatment cycles administered every three weeks. Clinical assessments included blood counts, kidney and liver function tests, and evaluations of neurotoxicity and hearing. Additionally, quality of life was measured using the Hospital Anxiety and Depression (HAD) scale and the Rotterdam Symptom Checklist.

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Key Findings

1. Treatment Completion Rates

• 58% of patients in the CDDP + GSH group completed all six cycles of treatment, compared to only 39% in the CDDP-only group (P = 0.04).
• Among patients who completed six cycles at the full 100 mg/m² dosage:
• 23% were in the CDDP + GSH group.
• 15% were in the CDDP-only group, although this difference was not statistically significant (P = 0.13).

2. Kidney Function (Nephrotoxicity)

• A significant reduction in kidney toxicity was observed in the GSH group:
• Decrease in creatinine clearance was 62% in the CDDP group versus 74% in the CDDP + GSH group (P = 0.006).
• Raised creatinine levels were found in 49% of the CDDP group, compared to 39% in the GSH group.
• Patients in the GSH group were significantly less likely to discontinue treatment due to kidney issues (P = 0.012).

3. Neurotoxicity and Hearing Loss

• Neurotoxicity (sensory nerve damage) was reported in:
• 49% of patients in the CDDP-only group.
• 39% of patients in the CDDP + GSH group, although the difference was not statistically significant (P = 0.22).
• Hearing loss (ototoxicity) was observed:
• In 25% of patients in the CDDP group.
• In 17% of patients in the CDDP + GSH group (P = 0.38).

4. Quality of Life Improvements

• Depression scores from the HAD scale showed significant improvement:
• The mean increase in depression score was 0.8 for the GSH group compared to 2.5 in the control group (P = 0.015).
• Patients receiving GSH reported fewer symptoms in:
• Nausea and vomiting
• Peripheral neuropathy (tingling in hands and feet)
• Hair loss
• Shortness of breath
• Difficulty concentrating
• Everyday activities, such as housekeeping and shopping, were better maintained in the GSH group (P < 0.05 for each improvement).

5. Weight Gain

• Patients in the GSH group gained an average of 2 kg during treatment, while the CDDP-only group showed no significant weight change (P = 0.010).

6. Tumor Response Rates

• Among the 80 patients whose clinical response could be evaluated:
• 73% of those in the CDDP + GSH group experienced partial or complete remission.
• 62% in the CDDP-only group showed similar outcomes, though this was not statistically significant (P = 0.25).
• A subgroup undergoing surgical restaging showed a statistically significant difference favoring GSH (P = 0.014), with complete remission observed in:
• 6 of 13 patients in the GSH group
• 1 of 11 patients in the CDDP group

7. Overall Survival

• No significant difference in overall survival between the two groups:
• Hazard ratio = 0.99 (95% CI: 0.61–1.61; P = 0.98).

Discussion and Implications

The study results suggest that glutathione supplementation with cisplatin offers significant benefits in terms of:

1. Reducing toxicity: Patients were less likely to suffer severe kidney and neurological damage.
2. Improving quality of life: Patients reported better physical well-being and fewer psychological effects (less depression and anxiety).
3. Enhancing treatment adherence: A larger percentage of patients were able to complete all six treatment cycles without dose reduction.

Interestingly, while survival rates and tumor response rates did not show statistically significant differences, the study suggested a positive trend toward better outcomes with GSH supplementation. This could be explored further with larger sample sizes or longer follow-up periods.

Conclusion

This study provides strong evidence that adding glutathione to cisplatin chemotherapy:

• Allows patients to complete more treatment cycles with fewer interruptions.
• Reduces toxic side effects, particularly on the kidneys and nervous system.
• Improves patient-reported quality of life.

Although glutathione did not significantly affect survival rates, its ability to reduce toxicity and allow more complete treatment cycles could indirectly contribute to better long-term outcomes. Further research is recommended to optimize dosage strategies and confirm long-term benefits.

For full details, refer to the original article: https://pubmed.ncbi.nlm.nih.gov/9261526/