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ObjectiveOxaliplatin is a cytotoxic agent frequently used in the treatment of gastrointestinal cancer patients. A known side effect of oxaliplatin administration via a peripheral vein is infusion-related pain. In this retrospective cohort study we compared the incidence of infusion-related pain in patients treated with oxaliplatin with or without simultaneous fluid infusion (FI) (800 mL glucose 5% in 2 hours).MethodsWe retrospectively defined two cohorts: Patients treated with oxaliplatin and simultaneous intravenous FI and the same number of patients treated without FI.The incidence of infusion-related venous pain was the primary outcome measure. Secondary outcomes included: Incidence of hypersensitivity reactions, infusion time, dose density, number of patients switched to a central venous catheter and incidence of peripheral neuropathy.Results100 patients were included, 50 patients in both groups. Baseline characteristics were comparable, except for age (median 66.8 vs 62.4 years in groups with and without FI; p=0.017), and body mass index (28.0 vs 25.7 kg/m2, respectively; p=0.012). Patients treated with simultaneous FI experienced significantly less vascular pain compared with those without FI (10% vs 78%, respectively; p<0.0001; OR 0.031 (95% CI: 0.01 to 0.098)). No difference was observed in dose density, treatment delay or the need of central venous catheter. Logistic regression analysis showed no confounders affecting the primary outcome. No adverse events of FI were observed.ConclusionConcurrent infusion of 800 mL glucose 5% with peripheral venous administration of oxaliplatin significantly reduces the incidence of infusion-related pain in gastrointestinal cancer patients and is highly feasible and affordable in everyday clinical practice.

3012 Background: Cell cycle faults are typical in cancer, with tumor cells depending on G2 checkpoints to avoid excess DNA damage. WEE1, a DNA damage-activated kinase, governs G2 by phosphorylating cyclin-dependent kinase 1 (CDK1) to arrest the cell cycle and permit DNA repair. Via CDK1 inhibition, WEE1 also blocks replication initiation, limiting oncogene-induced replication stress. WEE1 inhibition, with accumulating DNA damage, can induce mitotic catastrophe and apoptosis. Debio 0123, an orally available, ATP-competitive WEE1 inhibitor, is being studied as monotherapy and in combination with carboplatin (CP) in patients (pts) with solid tumors. Here, we report safety, pharmacokinetic (PK), pharmacodynamic, and antitumor activity data for the combination. Methods: Debio 0123-101 (NCT03968653) is a two-arm dose-escalation study in pts with advanced solid tumors that recurred or progressed after receiving platinum-containing therapy, where no standard therapy of proven benefit is available. In Arm A, Debio 0123 was given as monotherapy in cycle (C) 1 (as a single dose on day [D] -3 and once daily over D1–3) and in combination with CP from C2 until end of treatment (EOT). In Arm B, Debio 0123 was given in combination with CP on D1–3 and D8–10, from C1 to EOT. CP was given on D1 of each 21-day cycle in both arms. Skin biopsies were taken at baseline and C1D3 to assess target engagement (TE). Results: Arm A data (cut-off 31.12.2022) is shown. Overall, 38 pts were treated (78.9% female, mean age 58.5 years), with two pts ongoing. Using a continual reassessment method-guided dose escalation, tested Debio 0123 doses ranged from 30–520 mg. The maximum tolerated dose was declared at 520 mg. At this dose level, 2/6 pts experienced a dose-limiting toxicity. The treatment was deemed well tolerated, with a manageable safety profile in line with that expected for CP monotherapy. Most Debio 0123-related toxicities were grade 1/2. Preliminary PK data indicate that Debio 0123 plasma levels rise proportionally with dose. TE was seen from the 150 mg dose, becoming more pronounced with increasing dose levels. Confirmed partial responses (PR) occurred in 5/30 evaluable pts; 4/12 pts with platinum-resistant ovarian cancer achieved a PR (one ongoing). Conclusions: Debio 0123, combined with CP, has a manageable safety profile and is well tolerated up to 520 mg; this combination led to observable antitumor activity in pts with platinum-resistant cancer. Further study of Debio 0123 as a therapeutic agent is warranted. Clinical trial information: NCT03968653 . [Table: see text]