The most frequent side effects observed with the use of oxaliplatin, including in combination with fluorouracil / calcium folinate, were gastrointestinal reactions (diarrhea, nausea, vomiting, mucositis), hematologic (neutropenia, thrombocytopenia) and neurologic reactions (acute and cumulative dose-dependent peripheral sensory neuropathy). In general, these side effects were more frequent and severe with combination therapy of oxaliplatin with fluorouracil / calcium folinate, compared to monotherapy with these drugs.
Adverse reactions are listed according to the following gradation: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000 , <1/1000), very rarely (<1/10000, including individual messages), the frequency can not be estimated (the frequency can not be determined from the available data).
On the part of the hematopoiesis system: very often - anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia; often - febrile neutropenia (including 3-4 degrees), rarely - hemolytic anemia, autoimmune thrombocytopenia.
On the part of the digestive system: very often - nausea, vomiting, diarrhea, stomatitis, mucositis, abdominal pain, constipation; often - dyspepsia, gastro-esophageal reflux, gastrointestinal bleeding, rectal bleeding; infrequently - intestinal obstruction; rarely - colitis, including diarrhea caused by Clostridium difficile, pancreatitis.
From the liver and bile ducts: very rarely - a syndrome of hepatic sinusoidal obstruction, also known as veno-occlusive disease of the liver; endophlebitis of hepatic veins, incl. hepatic purpura (liver pelitis), nodular regenerative hyperplasia of the hepatic tissue, perisinusoidal fibrosis clinically manifested by portal hypertension and / or increased concentration of "hepatic" transaminases in the blood.
From the nervous system: very often - peripheral sensory neuropathy, sensitivity disorders, headache, taste disorder; often - dizziness, meningism, motor neuritis, depression, insomnia; infrequently - nervousness; rarely - dysarthria, reverse reversible leukoencephalopathy syndrome (SZOL); frequency can not be determined - convulsions.
Neurotoxicity is a dose-limiting side effect. Often the symptoms of sensory neuropathy are provoked by cold and are usually docked in the interval between courses. The duration of these symptoms increases with the total dose of oxaliplatin. Functional disorders that are manifested by the difficulty of performing precise movements are possible consequences of sensory damage. The risk of functional disorders for a total dose of about 850 mg / m2 (10 cycles) is about 10%, reaching 20% in the case of a total dose of 1020 mg / m2 (12 cycles). In most cases, neurologic symptoms decrease or disappear after discontinuation of therapy. However, in 3% of patients 3 years after the end of treatment, stable localized paresthesias of moderate intensity (2.3%) or paresthesia, affecting functional activity (0.5%) were observed.On the background of treatment with oxaliplatin, there were acute neurosensory manifestations, which usually occurred within a few hours after the administration of the drug and were most often provoked by cold. They were characterized by transient paresthesia, dysesthesia or hypoesthesia, rarely (1-2%) with an acute syndrome of laryngeal dysaesthesia. The latter was manifested by a subjective feeling of dysphagia and dyspnea without objective signs of respiratory distress syndrome (cyanosis or hypoxia), spasm of the larynx or bronchospasm (without stridor or wheezing). Also observed were such phenomena as spasm of chewing muscles, dysesthesia of the tongue, dysarthria and a feeling of pressure in the chest. Usually, these symptoms quickly stop as without the use of drug therapy, and with the introduction of antihistamines and bronchodilators. Increasing the infusion time during subsequent cycles of oxaliplatin therapy can reduce the incidence of this syndrome.
From the musculoskeletal system: very often - back pain; often - arthralgia, pain in the bones.
From the side of metabolism: very often - anorexia, hyperglycemia, hypokalemia,hypernatremia; often - dehydration, infrequently - metabolic acidosis.
From the respiratory system, chest and mediastinum: very often - shortness of breath, cough, nasal bleeding; often - hiccough, embolism pulmonary artery; rarely - pulmonary fibrosis, acute interstitial lung involvement, sometimes fatal.
From the cardiovascular system: often - bleeding, "hot flashes", thrombosis deep veins, increased arterial pressure.
From the urinary system: often - hematuria, dysuria; rarely - acute tubular necrosis, acute interstitial nephritis and acute renal failure; frequency can not be evaluated - haemolytic-uremic syndrome.
From the skin and subcutaneous tissues: very often - alopecia, skin rashes; often - peeling of the skin of the palms and feet (for example, palmar-plantar syndrome), erythematous rashes, rashes, increased sweating, changes with hand nails.
From the side of the organ of vision: often - conjunctivitis, visual impairment; rarely-transient reduction in visual acuity, loss of visual fields, optic neuritis, transient loss of vision, reversible after discontinuation of treatment.
From the organ of hearing: infrequently - ototoxicity, rarely - hearing loss, neuritis of the auditory nerve, deafness.
From the immune system: very often allergic reactions that occur mainly during infusion (skin rash, in particular urticaria, conjunctivitis, rhinitis); often anaphylactic reactions, including bronchospasm, angioedema, lowering of blood pressure and anaphylactic shock.
Infectious and parasitic diseases: very often - infections; often - rhinitis, infections of the upper respiratory tract, neutropenic sepsis.
Local reactions: very often - pain, redness, swelling and thrombosis at the injection site. Extravasation can also lead to local pain and inflammation up to necrosis, especially when oxaliplatin is injected into the peripheral vein.
From the laboratory indicators: very often - an increase in the concentration of alkaline phosphatase, the activity of "liver" enzymes, bilirubin, lactate dehydrogenase, changes in sodium and glucose in the blood serum; often - increasing the concentration of creatinine.
Other: very often - chills, fever due to the development of infections (with or without febrile neutropenia) or due to a possible immune mechanism, increased fatigue, weakness,pain, weight gain (with adjuvant therapy), often - weight loss (with the treatment of disseminated colorectal cancer).