Short-Term Fasting Around Chemotherapy May Improve Treatment Response in High-Grade Serous Ovarian Cancer

Marchetti C. et al. ASCO Annual Meeting 2026, Abstract 5517.

Background

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, frequently diagnosed at an advanced stage. Despite improvements in surgery and chemotherapy, recurrence rates remain high and long-term outcomes are often poor. Emerging evidence suggests that elevated insulin levels may promote tumor growth and reduce chemotherapy effectiveness. This pilot randomized study investigated whether short-term fasting (STF) around chemotherapy could improve metabolic parameters and enhance treatment response in patients receiving neoadjuvant chemotherapy for advanced HGSOC.

Study Design and Methods

This prospective, single-center, randomized pilot trial enrolled patients with newly diagnosed advanced HGSOC who were not candidates for primary cytoreductive surgery and required neoadjuvant chemotherapy. Eligible participants had a BMI ≥19 kg/m² and no diabetes, malnutrition, eating disorders, or significant food allergies.

Participants received standard carboplatin-paclitaxel chemotherapy and were randomized to one of two groups:

• Short-term fasting (STF): Fasting from 36 hours before chemotherapy until 24 hours after treatment completion, with a maximum intake of 350 kcal/day from permitted liquids and vegetable-based foods.

• Free diet: No dietary restrictions.

The primary endpoint was change in insulin levels after three chemotherapy cycles. Secondary endpoints included treatment response, progression-free survival (PFS), toxicity, and immune-related biomarkers.

Key Findings

Metabolic Effects

The study met its primary endpoint. After three cycles of neoadjuvant chemotherapy:

• Insulin levels increased by 9.76 µIU/mL in the free-diet group.

• Insulin levels decreased by 1.12 µIU/mL in the STF group.

These findings suggest that STF may counteract treatment-associated metabolic changes that could potentially support tumor growth.

Pathologic Response

Patients in the fasting group demonstrated substantially improved tumor response at interval cytoreductive surgery:

• 58.8% of STF patients achieved a Chemotherapy Response Score (CRS) of 3 (complete or near-complete response).

• 17.6% of patients in the free-diet group achieved CRS 3.

This represents more than a threefold improvement in optimal pathologic response among patients who fasted.

Progression-Free Survival

After a median follow-up of approximately 18 months:

• Median PFS was 38 months in the STF group.

• Median PFS was 24 months in the free-diet group.

Although the study was not powered primarily for survival outcomes, the 14-month difference suggests a potentially meaningful clinical benefit that warrants further investigation.

Safety and Tolerability

No significant differences in chemotherapy-related toxicity were observed between groups. Investigators reported that STF was generally safe and well tolerated, indicating that the intervention may be feasible in appropriately selected patients.

Immune Effects

Translational analyses showed lower levels of immunosuppressive granulocyte and monocyte populations in patients undergoing STF. These findings suggest that fasting may create a more favorable immune environment during chemotherapy, providing a possible biological mechanism for the observed improvements in treatment response.

Clinical Significance

This pilot study provides preliminary evidence that short-term fasting around chemotherapy may improve metabolic health, enhance tumor response, and extend progression-free survival in patients with advanced HGSOC. The intervention is low-cost, non-pharmacologic, and relatively easy to implement compared with many novel therapeutic approaches.

However, several limitations should be be considered:

• Small sample size (18 patients per arm analyzed).

• Single-center design.

• Results presented at ASCO and not yet published in a peer-reviewed journal.

• Survival outcomes require confirmation in larger, adequately powered trials.

• Findings may not be generalizable to patients with diabetes, malnutrition, low BMI, or other excluded conditions.

Expert Commentary

ASCO expert Dr. Eleonora Teplinsky described the findings as encouraging and consistent with earlier research on fasting and chemotherapy. She emphasized that larger clinical trials are needed to confirm efficacy, identify appropriate patient populations, and determine whether fasting can be safely incorporated into routine cancer care.

Conclusion

In this pilot randomized trial, short-term fasting before and after chemotherapy was associated with reduced insulin levels, significantly improved pathologic response rates, longer progression-free survival, and favorable immune changes in patients with advanced high-grade serous ovarian cancer. While the results are promising, larger randomized studies are necessary before STF can be recommended as a standard supportive care strategy during chemotherapy.