Neoplastic disease is a result of proliferation of abnormal cells. It can affect every system in the body and is a major cause of mortality and morbidity around the world.
Chemotherapy is used to kill neoplastic cells - however, there are usually a number of healthy cells which are also killed. The abnormal malignant cells take longer than the normal cells to grow. Therefore, chemotherapy is given in cycles to allow the 'normal' cells to recover.
Chemotherapy can be used for curative intent or palliation. It can be used alone or as an adjunct to other treatments - eg, surgery, hormonal therapy or radiotherapy. Often chemotherapeutic agents are used in combination but, occasionally, they are used alone.
November 2017 - Dr Hayley Willacy recently read this article looking at the efficacy of new cancer drugs. The key finding was that the majority of cancer drugs approved in Europe between 2009 and 2013 entered the market without clear evidence that they improved survival or quality of life for patients. Even where drugs did show survival gains over existing treatments, these were often marginal. Of 68 cancer indications approved during this period, 57% (39) came on to the market on the basis of a surrogate endpoint and without evidence that they extended survival or improved the quality of patients' lives. After a median of 5.9 years on the market, just six of these 39 (15%) agents had been shown to improve survival or quality of life. Of the 23 drugs that improved survival, 11 (48%) failed to meet the modest definition of "clinically meaningful benefit" set by the European Society of Medical Oncology. The researchers point out that the expense and toxicity of cancer drugs mean we have an obligation to expose patients to treatment only when they can reasonably expect an improvement in survival or quality of life. These results suggest this is not currently happening.
Main groups of chemotherapeutic agents
- Alkylating agents - eg, chlorambucil, carmustine, dacarbazine.
- Cytotoxic antibiotics - eg, doxorubicin, bleomycin.
- Antimetabolites - eg, 5-fluorouracil, 6-mercaptopurine, methotrexate.
- Topoisomerase inhibitors - eg, topotecan, etoposide.
- Mitotic inhibitors:
- Taxanes (such as paclitaxel)
- Vinca alkaloids (such as vincristine)
- Platinum compounds - eg, cisplatin.
Methods of administration of chemotherapy
- Others - eg, intravesical, subcutaneous
See individual drug monographs for details.
As a result of targeting healthy cells:
- Myelosuppression with possible anaemia, or increased susceptibility to infection or bleeding diathesis.
- Impaired wound healing.
- Nausea and vomiting.
- Mouth ulcers.
- Some agents may lead to menopausal symptoms in female patients - eg, alkylating agents in Hodgkin's lymphoma.
Safe use of cytotoxics
- Chemotherapy initiation is a decision made by oncology consultants.
- The first cycle must be prescribed by senior doctors; some hospitals say by consultants.
- Only trained personnel should administer cytotoxic agents.
- Gloves and eye protection are worn.
- Waste products are disposed of by incineration.
- Prior to administering cytotoxics, basic blood counts and appropriate other tests are checked - eg, LFTs.
- Patients may need antiemetics prior to drug delivery.
- Patients need to be aware that, for some agents, high concentrations are found in urine, sweat and vomit. They should be advised on appropriate clothing and how to dispose of soiled linen.
- Associated with pain, redness and inflammation. Very serious, as may lead to skin necrosis which could require limb amputation.
- There may be blotching of the skin or blistering and necrosis in severe cases.
- Treatment involves a high index of suspicion and careful monitoring if symptoms develop.
- Extravasation is reduced by administration of chemotherapeutic agents by trained personnel.
- The actual management of extravasation, once it has occurred, varies. Topical agents can be applied to act as antidotes - eg, dimethyl sulfoxide topically. In more severe cases, debridement and grafting may be necessary. However, the evidence base in this area is lacking and the best method is prevention[5, 6].
Nausea and vomiting
- Nausea and vomiting are a major cause of distress and reluctance for further therapy.
- Cytotoxic agents vary in their potency to cause vomiting, with agents such as, cisplatin and high-dose cyclophosphamide as highly potent and methotrexate and etoposide as least likely to cause vomiting.
- If the risk is low then agents such as domperidone and metoclopramide have good effect. With more emetogenic therapy, serotonin antagonists, such as ondansetron, are more effective.
- However, serotonin receptor antagonists are generally thought to be most useful with all forms of chemotherapeutic agents[9, 10].
Bone marrow suppression
- All cytotoxics, save a few, lead to myelosuppression. This tends to occur one week after administration of the agent.
- FBCs are checked prior to administration and should be checked in anyone presenting with fever or symptoms suggestive of infection following a course of chemotherapy.
- If the patient is neutropenic (<1.0 x 109/L) they will need urgent admission and assessment for neutropenic sepsis.
- This is reversible and varies between agents.
- Alopecia can have psychosocial consequences on patients in an already difficult situation.
- Again there is no clear evidence, but use of scalp hypothermic regimens may be helpful - eg, cold caps[12, 13, 14].
- Most agents are teratogenic so should not be given during pregnancy (although this needs to be a risk-benefit decision). They should also not be handled by pregnant personnel.
- Pre-treatment counselling and storage of sperm or ova and/or embryo formation may be appropriate. See 'Further reading & references' for more detailed information.
Further reading and references
Davis VJ; Female gamete preservation. Cancer. 2006 Oct 1107(7 Suppl):1690-4.
Rang HP, Dale MM, Ritter JM and Moore PK; Pharmacology, 5th ed, Bath, Churchill Livingstone. (2003) .
Davis C, Naci H, Gurpinar E, et al; Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13. BMJ. 2017 Oct 4359:j4530. doi: 10.1136/bmj.j4530.
De Bruin ML, Huisbrink J, Hauptmann M, et al; Treatment-related risk factors for premature menopause following Hodgkin lymphoma. Blood. 2008 Jan 1111(1):101-8. Epub 2007 Sep 21.
Schrijvers DL; Extravasation: a dreaded complication of chemotherapy. Ann Oncol. 200314 Suppl 3:iii26-30.
Wickham R, Engelking C, Sauerland C, et al; Vesicant extravasation part II: Evidence-based management and continuing controversies. Oncol Nurs Forum. 2006 Nov 2733(6):1143-50.
Perez Fidalgo JA, Garcia Fabregat L, Cervantes A, et al; Management of chemotherapy extravasation: ESMO-EONS Clinical Practice Guidelines. Ann Oncol. 2012 Oct23 Suppl 7:vii167-73.
Rugo HS; Management of chemotherapy-induced nausea and vomiting in clinical practice. Clin Adv Hematol Oncol. 2014 Mar12(3 Suppl 9):9-11.
Olver IN; Update on anti-emetics for chemotherapy-induced emesis. Intern Med J. 2005 Aug35(8):478-81.
Feeney K, Cain M, Nowak AK; Chemotherapy induced nausea and vomiting--prevention and treatment. Aust Fam Physician. 2007 Sep36(9):702-6.
Phillips RS, Gopaul S, Gibson F, et al; Antiemetic medication for prevention and treatment of chemotherapy induced nausea and vomiting in childhood. Cochrane Database Syst Rev. 2010 Sep 8(9):CD007786. doi: 10.1002/14651858.CD007786.pub2.
Choi EK, Kim IR, Chang O, et al; Impact of chemotherapy-induced alopecia distress on body image, psychosocial well-being, and depression in breast cancer patients. Psychooncology. 2014 Mar 24. doi: 10.1002/pon.3531.
Hesketh PJ, Batchelor D, Golant M, et al; Chemotherapy-induced alopecia: psychosocial impact and therapeutic approaches. Support Care Cancer. 2004 Aug12(8):543-9. Epub 2004 Jun 19.
Ekwall EM, Nygren LM, Gustafsson AO, et al; Determination of the most effective cooling temperature for the prevention of chemotherapy-induced alopecia. Mol Clin Oncol. 2013 Nov1(6):1065-1071. Epub 2013 Sep 6.
Lemieux J; Reducing chemotherapy-induced alopecia with scalp cooling. Clin Adv Hematol Oncol. 2012 Oct10(10):681-2.