History of cancer chemotherapy - Wikipedia
Nitrogen Mustard (Mechlorethamine) chemotherapy side effects, how it's given, how it works, Nitrogen Mustard is classified as an "alkylating agent. There is no relationship between the presence or severity of side effects and the. Mustard gas was originally used in the first world war, and even hair – the devastating side-effects of aggressive chemotherapy. had to try to make The Guardian sustainable by deepening our relationship with our readers. The origins of the first effective chemotherapy for cancer relied both on rigorous The effects of mustard gas on blood cells and bone marrow were first reported by Dr . American Association for Cancer Research, ;
However, reference to the first patient treated with chemotherapy was based on personal recollection rather than medical facts, as the chart had been misplaced.
Lost within this record was the personal and medical history of JD, a man whose illness sparked the birth of chemotherapy. John Fenn, clinical professor of surgery, and Dr. Robert Udelsman, professor and chair of the Department of Surgery, became curious and sought to uncover his story. To their surprise, the facts contained therein differed from those that had been previously reported, including inaccuracies in the personal history of JD, the circumstances surrounding his treatment, and his clinical course.
Fenn and Udelsman gave a captivating account of how chemotherapy was discovered and its first use at Yale. As Yale School of Medicine celebrates its th anniversary, we reflect on its pivotal contributions to the field of medicine. The discovery of chemotherapy at Yale serves as the quintessential model for scientific innovation: He lived in Connecticut and worked in a ball bearing factory until he became ill in August What began as tonsillar enlargement and right submandibular pain rapidly progressed to multiple enlarging masses that were biopsied and found to be lymphosarcoma.
Before long, they occupied the entire right side of his neck, and he could barely open his mouth. He underwent external beam radiation for 16 consecutive days with considerable reduction in tumor size and amelioration of his symptoms. However, his improvement was short lived, and by Junehe required additional surgery to remove cervical tumors. He underwent several more cycles of radiation to reduce the size of the tumors, but by the end of the year they became unresponsive and had spread to the axilla.
By Augusttwo years after the initial onset of symptoms, he suffered from respiratory distress, dysphagia, and weight loss, and his prognosis appeared hopeless. The treatment of lymphosarcoma at the time was surgical resection and radiation therapy, which had been shown to improve symptoms and prolong life [ 7 ]. However, relapse and death were common, and cases arising from the tonsils were reported to be most malignant [ 7 ].
The leukopenic effect of mustard gas on blood and bone marrow was first reported by Dr. Edward Krumbhaar in after treating exposed soldiers at a hospital in France [ 9 ]. He noticed a peculiar change in the hematological profile in these soldiers: Reports of severe toxicity prompted the U. Subsequently, Eve Wiltshaw and others at the Institute of Cancer Research in the United Kingdom extended the clinical usefulness of the platinum compounds with their development of carboplatina cisplatin derivative with broad antitumour activity and comparatively less nephrotoxicity.
Fludarabine phosphate, a purine analogue which has become a mainstay in treatment of patients with chronic lymphocytic leukaemia, was another similar development by Montgomery.
Anthracyclines and epipodophyllotoxins[ edit ] Other effective molecules also came from industry during the period of toincluding anthracyclines  and epipodophyllotoxins — both of which inhibited the action of topoisomerase IIan enzyme crucial for DNA synthesis. Supportive care during chemotherapy[ edit ] As is obvious from their origins, the above cancer chemotherapies are essentially poisons.
Patients receiving these agents experienced severe side-effects that limited the doses which could be administered, and hence limited the beneficial effects. Clinical investigators realized that the ability to manage these toxicities was crucial to the success of cancer chemotherapy.
Several examples are noteworthy. Many chemotherapeutic agents cause profound suppression of the bone marrow. This is reversible, but takes time to recover. Support with platelet and red-cell transfusions as well as broad-spectrum antibiotics in case of infection during this period is crucial to allow the patient to recover. Several practical factors are also worth mentioning.
Most of these agents caused very severe nausea termed chemotherapy-induced nausea and vomiting CINV in the literature which, while not directly causing patient deaths, was unbearable at higher doses.
The Birth of Chemotherapy at Yale
The development of new drugs to prevent nausea the prototype of which was ondansetron was of great practical use, as was the design of indwelling intravenous catheters e. Hickman lines and PICC lines which allowed safe administration of chemotherapy as well as supportive therapy. Bone marrow transplantation[ edit ] One important contribution during this period[ when?
The patient's bone marrow was first harvested, the chemotherapy administered, and the harvested marrow then returned to patient a few days later. This approach, termed autologous bone marrow transplantationwas initially thought to be of benefit to a wide group of patients, including those with advanced breast cancer.
However, rigorous studies have failed to confirm this benefit, and autologous transplantation is no longer widely used for solid tumors. The proven curative benefits of high doses of chemotherapy afforded by autologous bone marrow rescue are limited to both Hodgkin's and selected non-Hodgkin's lymphoma patients who have failed therapy with conventional combination chemotherapy. Autologous transplantation continues to be used as a component of therapy for a number of other hematologic malignancies.The Birth of Chemotherapy
Antihormone therapy[ edit ] The hormonal contribution to several categories of breast cancer subtypes was recognized during this time[ when? Targeted therapy[ edit ] bcr-abl kinase, which causes CMLinhibited by imatinib small molecule. Molecular genetics has uncovered signalling networks that regulate cellular activities such as proliferation and survival. In a particular cancer, such a network may be radically altered, due to a chance somatic mutation. Targeted therapy inhibits the metabolic pathway that underlies that type of cancer's cell division.
Tyrosine kinase inhibitors[ edit ] Further information: Bcr-Abl tyrosine kinase inhibitors The classic example of targeted development is imatinib mesylate Gleeveca small molecule which inhibits a signaling molecule kinase. The genetic abnormality causing chronic myelogenous leukemia CML has been known for a long time to be a chromosomal translocation creating an abnormal fusion protein, kinase BCR-ABL, which signals aberrantly, leading to uncontrolled proliferation of the leukemia cells.
Imatinib precisely inhibits this kinase. Unlike so many other anti-cancer agents, this pharmaceutical was no accident. He reasoned that precisely inhibiting this kinase with a drug would control the disease and have little effect on normal cells. Druker collaborated with Novartis chemist Nicholas Lydonwho developed several candidate inhibitors. From these, imatinib was found to have the most promise in laboratory experiments. It is hoped that molecular targeting of similar defects in other cancers will have the same effect.
Monoclonal antibodies[ edit ] Another branch in targeted therapy is the increasing use of monoclonal antibodies in cancer therapy. Although monoclonal antibodies immune proteins which can be selected to precisely bind to almost any target have been around for decades, they were derived from mice and did not function particularly well when administered to humans, causing allergic reactions and being rapidly removed from circulation.
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The faster the cells are dividing, the more likely it is that chemotherapy will kill the cells, causing the tumor to shrink.
They also induce cell suicide self-death or apoptosis.
Bicentennial: The Birth of Chemotherapy at Yale
Chemotherapy drugs that affect cells only when they are dividing are called cell-cycle specific. Chemotherapy drugs that affect cells when they are at rest are called cell-cycle non-specific. The scheduling of chemotherapy is set based on the type of cells, rate at which they divide, and the time at which a given drug is likely to be effective. This is why chemotherapy is typically given in cycles. Chemotherapy is most effective at killing cells that are rapidly dividing.
Unfortunately, chemotherapy does not know the difference between the cancerous cells and the normal cells. The "normal" cells will grow back and be healthy but in the meantime, side effects occur. Different drugs may affect different parts of the body.
Mechlorethamine is classified as an alkylating agent. Alkylating agents are most active in the resting phase of the cell. These drugs are cell cycle non-specific. There are several types of alkylating agents.
Mechlorethamine, Cyclophosphamide, Chlorambucil, Melphalan, and Ifosfamide. Altretamine, Procarbazine, Dacarbazine and Temozolomide. Carmustine, Lomustine and Streptozocin. Nitrosureas are unique because, unlike most chemotherapy, they can cross the blood-brain barrier. They can be useful in treating brain tumors. Carboplatin, Cisplatin, and Oxaliplatin. We strongly encourage you to talk with your health care professional about your specific medical condition and treatments. The information contained in this website is meant to be helpful and educational, but is not a substitute for medical advice.