Oncology · Medical Literature
Comparative safety of postoperative HIPEC with recombinant mutant TNF-α versus paclitaxel for gastric cancer peritoneal metastasis: a randomized controlled trial.
Abstract
Peritoneal metastasis (PM) of gastric cancer (GC) is frequently resistant to systemic chemotherapy, which leads to a poor prognosis. This study was designed to compare the safety and tolerability of hyperthermic intraperitoneal chemotherapy (HIPEC) with recombinant mutant human tumor necrosis factor-α (rmhTNF) versus paclitaxel after radical surgery for GC. Patients with locally advanced or metastatic GC who underwent surgical exploration at the Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University were prospectively enrolled and randomly assigned to three groups. All patients received HIPEC on the 1st and 3rd postoperative day. The HIPEC regimens were as follows: rmhTNF (Group A), paclitaxel (Group B), and rmhTNF + paclitaxel (Group C). A total of 30 patients were enrolled in this study, with 10 patients each in groups A, B and C. There were no statistically significant differences in postoperative first activity, gastrointestinal function recovery, catheter removal, and length of hospital stay (P > 0.05). Postoperative complications, including abdominal distension, discomfort, anastomotic leakage, myelosuppression, infection, and fever, did not demonstrate statistically significant differences among the three groups (P > 0.05). Similarly, no statistically significant differences were observed in hematology, liver and kidney function, and postoperative coagulation function among the three groups of patients before surgery, after the first HIPEC treatment, before the second HIPEC treatment, and after the second HIPEC treatment (P > 0.05). After a median follow-up of 14 months, a total of 10 patients (34.5%) experienced recurrence. The safety and tolerability of rmhTNF for HIPEC in GC were confirmed. Additionally, rmhTNF did not impede gastrointestinal recovery or increase postoperative complication rates.
Clinical relevance
In patients with locally advanced or metastatic gastric cancer undergoing radical surgery, is postoperative HIPEC with recombinant mutant human TNF-α (rmhTNF) comparable in safety and tolerability to HIPEC with paclitaxel or their combination? __SNAPSHOT__ {"studyDesign":"Randomized controlled trial (three-arm, parallel group)","setting":"Single center; Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, China","sampleSize":"n=30 (Group A [rmhTNF]: n=10; Group B [paclitaxel]: n=10; Group C [rmhTNF + paclitaxel]: n=10)","population":"Patients with locally advanced or metastatic gastric cancer who underwent surgical exploration; full inclusion/exclusion criteria not reported in abstract","intervention":"HIPEC with rmhTNF (Group A) or rmhTNF + paclitaxel combination (Group C), administered on postoperative days 1 and 3","comparator":"HIPEC with paclitaxel alone (Group B), administered on postoperative days 1 and 3","primaryOutcome":"Safety and tolerability, assessed via postoperative complications (including abdominal distension, discomfort, anastomotic leakage, myelosuppression, infection), time to first activity, gastrointestinal function recovery, catheter removal, and length of hospital stay","followUp":"Not reported (perioperative/in-hospital only based on abstract)","fundingSource":"Not reported"}
Key findings
Among 30 patients randomized equally across three groups, no statistically significant differences were observed across the three HIPEC regimens in time to first postoperative activity, gastrointestinal function recovery, catheter removal, or length of hospital stay (all P > 0.05). Postoperative complication rates — including abdominal distension, discomfort, anastomotic leakage, myelosuppression, and infection — did not significantly differ between groups (specific rates, absolute risk differences, confidence intervals, and p-values for individual complications are not reported in the abstract). The study concluded that rmhTNF was safe and tolerable for HIPEC use in gastric cancer, and did not impede gastrointestinal recovery or increase complication rates compared to paclitaxel. No efficacy outcomes (e.g., tumor response, progression-free survival, overall survival) were reported. NNT and NNH cannot be calculated from available data.
Practice implications
This pilot RCT provides preliminary evidence that rmhTNF is not inferior to paclitaxel in terms of short-term perioperative safety when used as a HIPEC agent following radical surgery for gastric cancer. However, several critical limitations constrain the interpretability and applicability of these findings. The study was powered exclusively for safety signal detection in a very small sample (n=10 per arm), and it is not clear whether it was formally powered at all for any specific hypothesis. The null results (P > 0.05) across recovery metrics should not be interpreted as proof of equivalence; the trial lacks the statistical power to reliably detect clinically meaningful differences in either safety or efficacy. No survival, recurrence, or tumor response data are reported, meaning the oncologic value of rmhTNF as a HIPEC agent remains entirely unestablished. This was a single-center Chinese cohort, limiting generalizability to other populations and healthcare settings. Only an abstract was available for review; the full methodology including randomization, allocation concealment, blinding, peritoneal carcinomatosis index stratification, and handling of missing data cannot be assessed. Practice should not change on the basis of this study alone. __LIMITATIONS__ Critically underpowered: n=10 per arm is insufficient to detect meaningful differences in safety outcomes or to exclude clinically important harms with acceptable precision.,Non-inferiority or equivalence hypothesis not formally pre-specified (based on abstract); null results at P > 0.05 cannot be interpreted as evidence of equivalence.,Only perioperative safety outcomes reported; no oncologic efficacy data (tumor response, disease-free survival, overall survival) presented.,Single-center design at a tertiary Chinese institution limits generalizability to other populations and practice environments.,Full methodological details (randomization method, allocation concealment, blinding strategy, baseline characteristics, peritoneal cancer index distribution) are unavailable from the abstract alone.,Follow-up duration is limited to the perioperative/in-hospital period; long-term safety signals (e.g., delayed myelosuppression, late anastomotic complications) are not captured.,Funding source not reported; potential conflicts of interest cannot be assessed.,Statistical approach for multiplicity of safety endpoints not described.,rmhTNF is not a standard HIPEC agent in Western practice, and its mechanism of intraperitoneal action and pharmacokinetics have not been established in this study. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ This small pilot RCT (n=30) found no statistically significant differences in perioperative safety or recovery metrics between HIPEC with rmhTNF, paclitaxel, or their combination following radical surgery for gastric cancer. However, the trial is severely underpowered, restricted to short-term safety endpoints, and reports no efficacy or survival data. These results are hypothesis-generating only and should not alter current clinical practice; adequately powered multicenter trials with oncologic endpoints are required before rmhTNF can be considered a viable HIPEC agent.