Highlights
- •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
Aim
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).
Patients and methods
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).
Results
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).
Conclusion
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.
Keywords
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Article info
Publication history
Published online: June 12, 2021
Accepted:
April 25,
2021
Received:
March 15,
2021
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
