1. Predictive factors of severe early treatment-related toxicity in patients receiving first-line treatment for metastatic colorectal cancer: Pooled analysis of 2190 patients enrolled in Fédération Francophone de Cancérologie Digestive (FFCD) trials
- Author
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Breton, Clémence, Aparicio, Thomas, Le Malicot, Karine, Ducreux, Michel, Lecomte, Thierry, Bachet, Jean-Baptiste, Taieb, Julien, Legoux, Jean-Louis, De Gramont, Aimery, Bennouna, Jaafar, Bouché, Olivier, Boussari, Olayide, Manfredi, Sylvain, and Gornet, Jean-Marc
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ALKALINE phosphatase , *CONFIDENCE intervals , *CANCER chemotherapy , *MULTIVARIATE analysis , *METASTASIS , *IRINOTECAN , *CELL receptors , *GASTROINTESTINAL diseases , *SEVERITY of illness index , *COLORECTAL cancer , *TREATMENT effectiveness , *RISK assessment , *FLUOROURACIL , *DESCRIPTIVE statistics , *VASCULAR endothelial growth factors , *OXALIPLATIN , *BEVACIZUMAB , *VASCULAR diseases , *ODDS ratio , *DRUG toxicity - Abstract
Few studies have explored the association between baseline characteristics and the occurrence of early toxicities in patients treated with first-line chemotherapy for metastatic colorectal cancer (mCRC). Individual patient data of 2190 patients enrolled in 10 prospective FFCD (Fédération Francophone de Cancérologie Digestive) trials were analysed. Severe early toxicity was defined as the occurrence of grade ≥III toxicity within 3 months after initiation of chemotherapy (ET3). Patients received monotherapy based on 5-FU (n = 1068), a cytotoxic doublet (n = 395) or tritherapy with a cytotoxic doublet plus anti-VEGF agent or a cytotoxic triplet (n = 727). The patients received 5-FU (100%), Irinotecan (39.6%), Oxaliplatin (13.4%), Bevacizumab (29.6%) or Aflibercept (1.8%). ET3 occurred in 244 patients (22.8%) with monotherapy, 248 patients (62.8%) with doublet and 392 patients (53.9%) with tritherapy. The most frequent ET3s were related to biological abnormalities and/or gastrointestinal, general and vascular disorders. The prognostic factors for the occurrence of an ET3 in multivariate analysis were a performance status of 2 rather than 0–1 (OR 2.57; 95% CI [1.16, 5.73]; p = 0.02), tritherapy versus monotherapy (OR 2.31; 95% CI [0.84, 6.33]; p = 0.02), alkaline phosphatase > 300 UI/l (OR 3.07; 95% CI [1.79, 5.27]; p < 0.001) and non-resected primary tumour versus resection (OR 1.59; 95% CI [1.06, 2.39]; p = 0.02). Median overall survival in patients without ET3 was significantly longer than that in patients with ET3 (HR 0.87; 95% CI [0.80–0.96]; p = 0.004). ET3 is frequent whatever the treatment regimen and is associated with certain baseline characteristics. The clinical impact of ET3 on prognosis in mCRC warrants further investigation. • Severe drug toxicity has a negative impact on prognosis in metastatic colorectal cancer. • Early toxicity within 3 months after first-line regimen initiation may be a key factor. • Early grade III or more toxicity is a new prognostic marker. • Some baseline characteristics are associated with ET3 occurrence. • Early grade III or more toxicity correlates with poorer overall survival. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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