| Ch 11 | Page 9 / 16 | |
| Cancer other treatments |
Rituximab | |
Rituximab is a genetically engineered chimeric murine/human monoclonal antibody against the CD20 antigen, comprising the constant regions of human IgG1 and the variant regions of light and heavy chains of murine immunoglobulin.
It is active against malignant cells presenting antigen CD 20, i.e. in follicular lymphoma (stage III and IV), in aggressive diffuse large B cell non-Hodgkin’s lymphoma.
This treatment is a major step in the treatment of lymphoma.
Rituximab infusion should be administered intravenously, in hospital, under the strict control of a competent oncologist or haematologist, with all necessary rehabilitation resources close to the patient (at least for the first infusion).
Premedication including an analgesic drug (paracetamol), an antihistaminic drug (diphenhydramine) and corticosteroids should be systematically given before every infusion of rituximab.
One of the most feared side effects is the cytokine release syndrome (see below).
More commonly, reactions are less severe and spontaneously stop when the infusion flow is slowed down.
At the beginning of the infusion, the flow rate of rituximab should be around 50 mg/hour; after the first thirty minutes, the flow rate can be progressively increased by 50 mg/hour every 30 minutes up to a maximum of 400 mg/hour.
Patients with major tumour mass or a high number of circulating malignant cells (>=25.000/ml) are the most exposed to the apparition of a severe cytokine release syndrome.
Its main characteristics are severe dyspnoea with bronchospasm and hypoxia associated with fever, shuddering, shaking, urticaria and angio-oedema. In the most severe cases, acute respiratory insufficiency can lead to death. This acute respiratory insufficiency is related to an interstitial pulmonary infiltrate or pulmonary oedema.
This syndrome usually appears during the first or second hour following the beginning of the first infusion.
For this reason, very precise monitoring should be implemented during this first infusion. The infusion should be stopped if any abnormality is observed, and drastic symptomatic treatment instituted.
This syndrome is observed in approximately 10% of first infusions although it is generally less dramatic.
The cytokine release syndrome can be followed by a tumour lysis syndrome (when very massive tumours are present).
This syndrome is characterised by a hyperuricaemia, hyperkaliemia, hypocalcaemia, increased LDH and acute renal insufficiency.
Therefore, rapid recovery from a cytokine release syndrome may be followed by a rapid deterioration.
The tumour lysis syndrome should be prevented using hypouricemic drugs and extensive hydration.
After such acute syndromes and their full recovery, patients treated again with a much slower flow rate, rarely experience further severe cytokine release.
The response rates to rituximab in B cell follicular non-hodgkin’s lymphoma or in low grade lymphoma, relapsing or resisting to chemotherapy, are in the range of 50%. The responses are generally long-lasting.
However, many trials are currently in progress associating retuximab with classical chemotherapy regimens (like CHOP), and the indications of rituximab are changing with very encouraging results published each year.
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