Since alkylating agents are designed and intended to destroy human cells (tumors are, after all, collections of abnormal human cells of a particular type), inevitably non-cancerous cells will be destroyed as well. The most common toxicities (side-effects) that occur as a consequence of alkylating agent administration used as cancer chemotherapy are related to the destruction of normal cells.
Alkylating agents are known to cause a dose-dependent destruction of certain cells of the immune system. In the treatment of autoimmune diseases, this is occasionally an advantage (such as with cyclophosphamide), but in cancer treatment it can cause severe immunosuppression. This state makes cancer patients treated with these drugs particularly susceptible to certain infections, including infections by microorganisms that do not often infect people with a normal immune system (e.g. fungi). Another common side-effect related to cellular destruction affects rapidly dividing cells, such as mucosal cells. This becomes clinically apparent in damage done to the oral mucosa and to the lining of the gastrointestinal tract—bleeding gums and copius, sometimes bloody diarrhea can occur. Poor absorption of nutrients across the GI tract can take place as well.
There are quite a few side effects for cisplatin, yet despite these side
effects, many doctors and patients continue its use. However, for some
these side effects will cause conflicts due to other medications or comorbid
conditions while others choose to not use cisplatin in favor of newer
medications which have fewer and less severe side effects. Its widespread
use is due to it effectiveness in treating certain types of cancer, so
the benefits outweigh the detractions in certain cases. Also, since cisplatin
has well-known and widely documented effects and side-effects, it can
be used as a base treatment to provide consistent care for the patient
while testing the effectiveness and side effects of another drug.
The following are some side effects of cisplatin:
- Nephrotoxicity - causes damage to the kidneys
- Neurotoxicity - causes damage to the nerves
- Nausea and vomiting - one of the most likely to cause severe nausea and vomiting
- Ototoxicity - hearing loss which is currently not treatable
- Alopecia - hair loss, not a common side effect
- Electrolyte imbalance - causes various problems with cell operation
- Decrease of blood cells in bone marrow
- Thrombocytopenia (low blood platelet count)
- Leucopenia (low white blood cell count)
- Myelosuppression (decrease in bone marrow effectiveness)
- Changes in how food tastes
- Frequent diarrhea
- Numbness in the extremeties
- Extreme fatigue
The toxicity of alkylating agents widely believed to result from the formation of lesions that block polymerases or disrupt the integrity of the genome. The side effects are generally reversible and subside when treatment ends. However, renal toxicity is cumulative, and can result in complications months after treatment ends. Myelosuppression also accumulates over the course of the treatment, but it subsides with the end of treatment.
Research into Cisplatin and its function
Classes of alkylating antineoplastic agents
| Nitrogen mustard analogues |
| Alkyl sulfonates |
| Ethylene imines |
| Nitrosoureas |
| Triazenes (Nonclassical) |
Occasionally severe organ damage can occur with the administration of alkylating agents. Pulmonary fibrosis and venoocclusive disease of the liver has occurred across all types of drugs within the class. The use of nitrosureas has been associated with renal failure.
The central nervous system can be affected by alkylating agents as well. In addition to severe nausea and vomiting common to the class, certain agents (e.g. Ifosfamide) is quite neurotoxic, leading to acute confusion and delirium, seizures, paralysis, and coma.
Alopecia (hair loss) is known to occur with alkylating agents. Sex organs
are not spared—women that are treated with alkylating agents may experience
permanent amenorrhea (lack of menstruation) and in men, sperm production
may cease,