Cancer chemotherapy refers to a "wide range of therapeutic options used in the treatment of malignant diseases, including categories such as cytotoxic drugs, biologics, immunotherapies, targeted drug therapies, hormonal treatments, and high dose chemotherapy regimens supported with hematopoietic stem cell transplant". This course provides an overview of chemotherapeutic agents, modes of action, methods of administration and common side effects (Zhang n.d.).
Modern medical treatment of cancer evolved from the discovery that mustard gas exposure during World War I resulted in leukopenia and mutations that increased the risk of leukemia and lymphoma. During WWII, Yale scientists Louis Goodman and Alfred Gilman discovered that the nitrogen mustard gas, being studied for weaponization, also had the ability to shrink certain cancer tumors (Schiff 2011).
In 1948, the UK chemist, Professor Alexander Haddow, demonstrated that two chlorine atoms on the nitrogen mustard molecule were needed to kill cancer cells. "He continued his research, showing how these chemicals actually worked – it was by somehow linking together other molecules inside the cancer cell, ultimately leading the cell on a suicidal path (Haddow 1963).
The same year, Sidney Farber "demonstrated that a number of folic acid antagonists, including 4-aminopteroyl-glutamic acid (aminopterin) produced temporary remissions in children with acute undifferentiated leukaemia. These observations lead to the development and use of other chemotherapeutic agents, either singly or, more effectively, in combination for treating childhood and adult malignancies. He introduced actinomycin D for the treatment of metastatic and localized Wilms tumour" (Miller D.R. 2006).
Cytotoxic drugs remain a principal component of many cancer treatment protocols. Today, cytotoxic antineoplastic drugs are FDA approved to cure cancer, to prolong life, or to provide palliation when reducing tumor size can relieve pain or other distressing symptoms. Cytotoxic drugs work primarily by interfering with completion of the cell replication cycle.
When a cell cannot pass through all phases of the cell cycle the result may be programmed cell death known as apoptosis or necrosis. Cytotoxics have their greatest effect on cells and cancers that have rapid replication rates. Certain cancers as well as healthy hair follicle cells, bone marrow cells, and cells lining the mouth and gut replicate frequently making them more susceptible to the effects and side effects of cytotoxic medicines. Other healthy tissues like muscle, heart, brain, and bone replicate less often and are therefore less effected by cytotoxic drugs. Unfortunately, the usefulness of all cytotoxic regimens are limited by the side effects on healthy cells (Gale 2020).
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"The majority of curable cancers are uncommon tumours such as childhood cancers, leukaemias, lymphomas and testicular tumours. Other cancers are partially responsive but the impact of chemotherapy on survival in advanced solid tumours is less (although important). These include cancer of the breast, SCLC, ovarian cancer and cancer of the colon." "The overall contribution of chemotherapy to cure is relatively small" Hochhauser, D., & Tobias, J. (2015).
Single-drug chemotherapy may cure selected cancers (eg, choriocarcinoma, hairy cell leukemia). More commonly, cytotoxic drugs with different mechanisms of action are combined. Combination cancer therapy protocols are designed to, optimize treatment effect and quality of life while minimizing side effects and cancer cell resistance. Combination regimens can provide significant cure rates (eg, in acute leukemia, testicular cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, and, less commonly, solid tumors such as small cell lung cancer and nasopharyngeal cancer). Multidrug regimens typically are given as repetitive cycles of a fixed combination of drugs. The interval between cycles should be the shortest one that allows for recovery of normal tissue (Gale 2020).
Reference
Gale R.P. (2020). Systemic Cancer Therapy. Merck Manual, Professional Version. Retrieved January 18, 2022. from, https://www.merckmanuals.com/professional/hematology-and-oncology/principles-of-cancer-therapy/systemic-cancer-therapy
HADDOW A. SYMPOSIUM ON CHEMOTHERAPY OF CANCER. GENERAL INTRODUCTION. Proc R Soc Med. 1963;56(8):629-631. Retrieved January 18, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1897413/?page=1
Hochhauser, D., & Tobias, J. (2015). Cancer and its management. John Wiley and Sons.
Miller, D. R. (2006). A tribute to Sidney Farber – the father of modern chemotherapy. Wiley Online Library. Retrieved January 19, 2022, from https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2006.06119.x
Schiff J.A. (2011). Pioneers in chemotherapy. Old Yale | Yale Alumni Magazine. Retrieved January 18, 2022, from https://yalealumnimagazine.com/articles/3173-pioneers-in-chemotherapy
Zhang. (n.d.). Chemotherapy. CancerQuest. Retrieved January 18, 2022, from https://www.cancerquest.org/patients/treatments/chemotherapy
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