Jaime Rafael Merchan

Background/Objectives: Fasting has been proposed as a non-pharmacologic method of reducing chemotherapy toxicity. However, its effects across outcome domains have not been well-quantified. Methods: In line with PRISMA 2020 guidelines (PROSPERO: CRD420261296778), we searched PubMed, Embase, Web of Science, and CENTRAL from January 2015 through April 2026 for randomized or prospective comparative trials evaluating fasting during chemotherapy. Risk of bias was assessed using RoB 2 and criteria aligned with ROBINS-I. Standardized mean differences (Hedges’ g) and risk ratios (RRs) were pooled using three-level random-effects models. Results: Seven publications reporting six trials (268 participants) were included. The pooled estimate did not reach statistical significance (g = 0.21, 95% CI: −0.02–0.43, p = 0.064). Hematologic parameters (g = 0.11, 95% CI: −0.23–0.45) and quality of life (QoL) and patient-reported outcomes from one trial (g = 0.32, 95% CI: −0.03–0.66) did not differ significantly between groups. Adverse events also did not differ significantly (RR = 0.86, 95% CI: 0.55–1.36). Conclusions: Across six small trials, fasting during chemotherapy did not significantly affect hematologic parameters, QoL, or adverse events. However, it is worth nothing that point estimates generally favored fasting. Hence, a small benefit can neither be confirmed nor ruled out at this time. Adequately powered trials assessing patient-important outcomes and incorporating nutritional monitoring are needed before fasting can be recommended or ruled out.

Study population representativeness

Trial schema for parts 1–3. *Expansion cohort into patients with neuroendocrine tumors (NET). Based on the lack of efficacy in the combination arm, further monotherapy expansion cohorts were abandoned. † Labeled dose/regimen of avelumab. ‡ Combination therapy safety lead in. No attrition was observed.

Part 1 disease response and SPECT/CT positivity

Injection volume, site size and image guidance criteria

IRRs and CRS related to intravenous VV1 monotherapy (part 2).

DLT definition VV1 combination therapy

Serum IFNß and cytokine levels following VV1 monotherapy and in combination with avelumab. A, Mean serum IFNß following IT administration of VV1 monotherapy dose escalation (part 1). Each DL has 3–6 patients. B, Serum IFNβ following 30–90-minute IV infusions of high-dose VV1 (1 × 1011 TCID50) monotherapy (part 2). Each line represents a unique patient (n = 6). C, Mean [95% confidence interval (CI)] serum IFNβ following IV infusions of VV1 (1.7 × 1010 TCID50) monotherapy (part 2). Each dot represents a unique patient (n = 23). Limit of detection for IFNβ was 1.2 pg/mL. D, Mean (95% CI) serum IFNβ over time following 30-minute IV infusions of VV1 (1.7 × 1010 TCID50) + labeled dose/regimen of avelumab (part 3). Each dot represents a unique patient (n = 16). Limit of detection for IFNβ was 1.2 pg/mL. E, Mean (±SEM) cytokine levels following 30-minute IV infusion of VV1 (1.7 × 1010 TCID50) monotherapy (part 2; n = 7). F, Mean (±SEM) cytokine levels following 30-minute IV infusion of high dose VV1 (1 × 1011 TCID50) monotherapy (part 2; n = 6).