Thrombopoietin Receptor Agonists for Chemotherapy-Induced Thrombocytopenia in GI Cancers—A Big Solution for a Small Problem or a Solution at All?
Mené sur 23 patients atteints d'un cancer gastrointestinal, cet essai multicentrique de phase II évalue l'intérêt de l'avatrombopag pour prendre en charge une thrombocytopénie persistante induite par la chimiothérapie
Chemotherapy dose reductions, delays, and discontinuations are thought to affect treatment outcomes for patients with GI cancers, both in the perioperative curative-intent setting and for patients with advanced disease. Several studies suggest that chemotherapy relative dose intensity (RDI, the amount of chemotherapy delivered compared with the amount of chemotherapy intended), with cutoffs usually between 70% and 85%, may influence disease-free, progression-free, and overall survival.1-6 Common chemotherapies for GI cancers include 5-fluorouracil (5-FU)– or gemcitabine-based regimens and most frequent related toxicities, and hence, reasons for reduced RDI are constitutional, GI, hematologic, and neuropathic toxicities. Approximately 50% of patients with GI cancer undergo at least one dose reduction, up to 70% have dose delays, and almost 30% stop treatment because of chemotherapy-related toxicities.3 Many factors including age, sex, comorbidities, performance status, and disease characteristics affect chemotherapy RDI,7,8 with the elderly being more susceptible to hematologic toxicity.9 Despite evidence that maintaining RDI may be important for long-term outcomes, especially for cancers treated with curative intent, several chemotherapy dose and schedule adjustments are not associated with worse survival in the palliative, metastatic setting, but instead they improved tolerability and quality of life. One such example is the discontinuation of 5-FU bolus from 5-FU–based regimes to alleviate nausea, vomiting, and myelosuppression10,11 or modifying folinic acid, 5-FU, irinotecan, and oxaliplatin with dose reductions for oxaliplatin and irinotecan, with comparable responses and survival rates but improved tolerability versus the standard regimen.12,13 Similarly, de-escalation strategies after 3-4 months of induction therapy have no detrimental impact on survival and thus are listed as maintenance options in National Comprehensive Cancer (NCCN) guidelines.14-17 Nevertheless, the threshold of 75%-80% RDI appears to correlate with long-term survival in several analyses, highlighting the perceived need for interventions to improve dose intensity.5,6 Ultimately, supportive care tailored to the needs of each patient is paramount for not just the longest, but the best survival.
Journal of Clinical Oncology , éditorial, 2026