Chemotherapy toxicity and dose adjustment
nausea or vomiting, Toxicities, diarrhea, toxicity, toxicities, neurotoxicity, mucositis, failure of hematological recovery, hematologic or gastrointestinal (GI) toxicity
FEBRILE NEUTROPENIA, THROMBOCYTOPENIA, MUCOSITIS, HAND-FOOT SYNDROME, INFUSION REACTION
Dose reduction is planned in case of severe haematological and/or non haematological toxicities. Dose adjustments are to be made according to the system showing the greatest degree of toxicity. Toxicities will be graded using the NCI CTC, version 5.0. Treatment will be delayed until: neutrophils ≥ 1.5 × 105FU dose-modification:Recovery from mucositis, diarrhea. If 5-FU treatment is delayed, then the associated oxaliplatin dose should also be delayed. If 5-FU is discontinued permanently, oxaliplatin should also be discontinued. If toxicity requires a dosing delay of more than four weeks, the subject will be permanently withdrawn from the study treatment for toxicity. Dose modifications for hematologic or gastrointestinal (GI) toxicity will be based on the worst toxicity observed during the previous cycle. After recovery, standard dose adjustments for 5-FU toxicity should be applied. The dose of 5-FU should be reduced by 20% in subsequent cycles for the following toxicities: febrile neutropenia, grade 4 thrombocytopenia, or failure of hematological recovery to neutrophils ≥1500 /mL and platelets ≥75000/mL within 2 weeks of the scheduled start of the next treatment cycle; grade 3-4 mucositis, diarrhea, or nausea or vomiting in spite of optimal antiemetic prophylaxis. In the mFOLFOX6 protocol, the bolus 5FU should be interrupted before the aforementioned reduction of the continuos infusion 5FU. A second dose reduction of 5-FU of 20% from the original dose may be made if the above toxicities recur. After reductions of doses, they should not be increased again and must be carried on to the rest of the treatment.Capecitabine:Patients with a creatinine clearance of 30-50 mL/min must commence treatment with CAPE at 75% of the full dose. Dose modifications for hematologic, skin or GI toxicity will be based on the worst toxicity observed during the previous cycle. After recovery, standard dose adjustments for capecitabine toxicity should be applied. The dose of capecitabine should be reduced by 25% in subsequent cycles for the following toxicities: febrile neutropenia, grade 4 thrombocytopenia, or failure of hematological recovery to neutrophils ≥1500 /mL and platelets ≥75000/mL within 2 weeks of the scheduled start of the next treatment cycle; grade 3-4 mucositis, hand-foot syndrome, diarrhea, or nausea or vomiting in spite of optimal antiemetic prophylaxis.Oxaliplatin;If a second dose reduction of 5FU is performed, oxaliplatin dose must also be reduced by 25%. Oxaliplatin neurotoxicity should be assessed before every oxaliplatin dose. If neurotoxicity is grade 3, oxaliplatin dose should be reduced by 25%. If toxicity is grade 4, oxaliplatin should be discontinued permanently. For oxaliplatin infusion reactions grade 2 or less occur, oxaliplatin can have its infusion time extended until 6 hours and the patient must receive pre medications such as H1 antagonists, H2 antagonists and corticosteroids. If it recurs or is graded 3 or more, oxaliplatin administration must be suspended. Where it is available, desensitization protocols can be applied, 5FU may continue even if oxaliplatin is discontinued.