Kinetically guided neoadjuvant chemoradiotherapy based on 5-Fluorouracil in patients with locally advanced rectal cancer
| Autor: | Jiří, Grim, Miloš, Hroch, Hroch, Miloš, Jaroslav, Chládek, Chládek, Jaroslav, Jiří, Petera, Petera, Jiří, Jiřina, Martínková, Martínková, Jiřina |
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| Rok vydání: | 2014 |
| Předmět: |
Pharmacology
Male Antimetabolites Antineoplastic Rectal Neoplasms Chemoradiotherapy Middle Aged Combined Modality Therapy Neoadjuvant Therapy Antineoplastic Combined Chemotherapy Protocols Humans Pharmacology (medical) Female Fluorouracil Prospective Studies Infusions Intravenous Aged Follow-Up Studies Neoplasm Staging |
| Zdroj: | Clinical pharmacokinetics. 54(5) |
| ISSN: | 1179-1926 |
| Popis: | This study estimated patients' early response following neoadjuvant chemoradiotherapy (CHRT) of locally advanced rectal cancer based on 5-fluorouracil (5-FU). The target was to achieve pathological complete response (pCR; residual disease-free stage) and toxicities of grade ≤2, using individual dosing predicted according to the steady-state plasma concentration (C ss) and pharmacokinetic parameters of 5-FU: the area under the time-concentration curve at steady state (AUC) and clearance (CL).This open-label prospective study enrolled 33 adult patients treated with 5-FU administered as a continuous intravenous infusion over 4-5 weeks, as follows: in Group 1a (N = 6), the patients received a standard dose of 300 mg/m(2)/24 h. In Group 1b (N = 7), the patients were treated with an escalated dose of 400-1,000 mg/m(2)/24 h. In Group 2 (N = 20), the patients were given dosing kinetically guided in order to reach the target range of 5-FU C ss 50-100 µg/L. Tolerability was tested according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Radiotherapy was delivered with 10-15 MV photon beams at 1.8 Gy/fraction up to 50.4 Gy in 28 daily fractions for 5 days a week. Surgery followed 4-6 weeks after the completion of CHRT and clinical restaging. The pCR and residual tumour stage were evaluated using preoperative tumour downstaging in magnetic resonance, postoperative histopathological staging and tumour regression rate (residual disease).The cumulative AUC of 5-FU (total exposure to the drug) correlated with cumulative 5-FU dose (r = 0.61; p0.001) and residual disease (r s = -0.53; p0.005). A higher target pCR rate was reached in patients individually treated (Group 2) who finished the whole 5-week CHRT. The individual daily dose needed to reach the target C ss should be350 mg/m(2) (up to 600 mg/m(2)) provided that 5-FU metabolic ratio is within the range of 2.5-6 and the cumulative AUC5wks is within 50-100 mg·h/L. |
| Databáze: | OpenAIRE |
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