Cisplatin reacts with metallic aluminium to form a black precipitate of platinum. All aluminium containing IV sets, needles, catheters and syringes should be avoided.
Cisplatin must be administered under close supervision by a qualified doctor specialized in the use of chemotherapeutic agents.
Appropriate monitoring and management of the treatment and its complications are only possible if adequate diagnosis and exact treatment conditions are available.
Before, during and after administration of cisplatin, the following parameters resp. organ functions must be determined:
– Renal function;
– Hepatic function;
– hematopoiesis functions (number of red and white blood cells and blood platelets);
– Serum electrolytes (calcium, sodium, potassium, magnesium).
These examinations must be repeated every week over the entire duration of the treatment with cisplatin.
Repeating administration of cisplatin must be delayed until normal values are achieved for the following parameters:
– Serum creatinine ≤ 130 μ mol/l resp. 1.5 mg/dl
– Urea <25 mg/dl
– White blood cells >4.000/μ l resp. >4.0 x 109/l
– Blood platelets >100.000/μ l resp. >100 x 109/l
– Audiogram: results within the normal range.
Nephrotoxicity
Cisplatin causes severe cumulative nephrotoxicity which may be potentiated by other substances . A urine output of 100 mL/hour or greater will tend to minimize cisplatin nephrotoxicity. This can be accomplished by pre-hydration with 2 liters of an appropriate intravenous solution, and similar post cisplatin hydration (recommended 2,500 mL/m2/24 hours). If vigorous hydration is insufficient to maintain adequate urinary output, an osmotic diuretic may be administered (eg, mannitol).
Neuropathies
Severe cases of neuropathies have been reported. These neuropathies may be irreversible and may manifest by paraesthesia, areflexia and a proprioceptive loss and a sensation of vibrations. A loss of motor function has also been reported. A neurologic examination must be carried out at regular intervals.
Ototoxicity
Ototoxicity has been observed in up to 31% of patients treated with a single dose of cisplatin 50mg/m2, and is manifested by tinnitus and/or hearing loss in the high frequency range (4000 to 8000Hz). Decreased ability to hear conversational tones may occur occasionally. Ototoxic effect may be more pronounced in children receiving cisplatin. Hearing loss can be unilateral or bilateral and tends to become more frequent and severe with repeated doses; however, deafness after initial dose of cisplatin has been reported rarely. Ototoxicity may be enhanced with prior simultaneous cranial irradiation and may be related to peak plasma concentration of cisplatin. It is unclear whether cisplatin induced ototoxicity is reversible. Careful monitoring by audiometry should be performed prior to initiation of therapy and prior to subsequent doses of cisplatin. Vestibular toxicity has also been reported.
Allergic phenomena
As with other platinum-based products, hypersensitivity reactions appearing in most cases during perfusion may occur, and necessitate discontinuation of the perfusion and an appropriate symptomatic treatment. Cross reactions, sometimes fatal, have been reported with all the platinum compounds.
Hepatic function and hematological formula
The hematological formula and the hepatic function must be monitored at regular intervals.
Carcinogenic potential
In humans, in rare cases the appearance of acute leukemia has coincided with use of cisplatin, which was in general associated with other leukemogenic agents.
Cisplatin is a bacterial mutagen and causes chromosome aberrations in cultures on animal cells. Carcinogenicity is possible but has not been demonstrated. Cisplatin is teratogenic and embryotoxic in mice.
Injection site reactions
Injection site reactions may occur during the administration of cisplatin. Given the possibility of extravasation, it is recommended to closely monitor the infusion site for possible infiltration during drug administration. A specific treatment for extravasation reactions is unknown at this time.
Cisplatin has been shown to be mutagenic. It may also have an anti-fertility effect. Other anti-neoplastic substances have been shown to be carcinogenic and this possibility should be borne in mind in long term use of cisplatin.
This cytostatic agent has a more marked toxicity than is usually found in antineoplastic chemotherapy.
Renal toxicity, which is above-all cumulative, is severe and requires particular precautions during administration.
Nausea and vomiting may be intense and require adequate antiemetic treatment.
Prophylactic administration of an anti-emetic may be effective in alleviating or preventing nausea and vomiting.
The liquid loss caused by vomiting and diarrhoea must be compensated.
Close supervision must also be carried out with regard to ototoxicity, myelodepression and anaphylactic reactions.
