Have you ever wondered where cancer drugs come from? When I was diagnosed with Stage IV bladder cancer in 2008 I wanted to know where my donated monies were going and, more specifically, what good the drugs I was told to take were going to do. With only a few months to love, or so I was informed, I decided to go my own quest to find out, since I wanted the last few months of my life to be a good as I could make them. What emerged was rather disturbing.
My chemotherapy regime involved the administration of the following drugs: Methotrexate, Vinblastine, Doxorubicin (Adriamycin), and Cisplatin or MVAC. This is the usual protocol for transitional cell carcinoma of the bladder. The prognosis for Stage IV TCC is rather grim. Four percent of patients with a metastatic disease usually become long-term survivors following chemotherapy treatment, although the median survival rate is often a year. When I met with my oncologist before treatment I was told that she didn’t know if these drugs would work. I was told to hope for the best.
Methotrexate has been around since 1947. It initially came into being because it was considered less toxic than more common treatments —given the list of side-effects I can only imagine how toxic the other treatments must have been. Sadly any of the research I did on the efficacy of Methotrexate was very disheartening with most citing, “that although it had some effect on cancer, there was very little research to support survival.”
Vinblastine has an even more storied past. It has been around since 1958. It was isolated by Robert Noble and Charles Thomas Beer at the University of Western Ontario (my alma mater). It is obtained from the leaves of young Madagascan Periwinkle plants. This is the only known source for Vinblastine, which makes the drug extremely expensive —ranging from $2-20 million/kilo. Scientists all over the world have been trying to devise a way of making a synthetic drug in the laboratory, but so far attempts have failed. As a result, huge fields of Madagascan Periwinkles are grown mainly in China and India to extract the drug. Again any research I did on the efficacy of Vinblastine netted less than stellar results.
What I find ironic is that at present a great debate is ongoing about the effects of another plant, cannabis, on cancer. Last time I checked cannabis costs much less to cultivate. But I will save further discussion on this topic for my next column.
Doxorubicin has an even more interesting past. It was approved for medical use in the United States in 1974 and was originally made from the bacteria Streptomyces peucetius.
In the 1950s an Italian research company, Farmitalia Research Laboratories, began an organized effort to find anti-cancer compounds from soil-based microbes. A soil sample was isolated from the area surrounding the Castel Del Monte, a 13th-century castle. A new strain of Streptomyces peucetius, which produced a red pigment, was isolated, and an antibiotic from this bacterium was effective against tumors in mice. Since a group of French researchers discovered the same compound at about the same time, the two teams named the compound Daunorubicin, combining the name Dauni, a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for ruby, rubis, describing the color. Clinical trials began in the 1960s, and the drug was successful in treating acute leukemia and lymphoma. However, by 1967, it was recognized that Daunorubicin could produce fatal cardiac toxicity.
Researchers at Farmitalia soon discovered that changes in biological activity could be made by minor changes in the structure of the compound. A strain of Streptomyces was mutated using N-nitroso-N-methyl urethane, and this new strain produced a different, red-colored antibiotic. They named this new compound Adriamycin, after the Adriatic Sea, and the name was later changed to Doxorubicin to conform to the established naming convention. Doxorubicin showed better activity than Daunorubicin against mouse tumors and especially solid tumors. It also showed a higher therapeutic index, yet the cardiotoxicity remained. (Source: Wikipedia)
Doxorubicin is nicknamed “the red devil”. If you have ever had to have it, you’d remember it. It is the devil! Some of its many side-effects include hair loss, short term memory loss, nausea, loss of appetite, stomach pains, loss of sleep, sweats, mouth sores, watery eyes, neuropathy, and on and on…nasty, nasty stuff. I wouldn’t wish it on my worst enemy. I hope you never need it.
The efficacy of Doxorubicin showed some very positive results initially. Unfortunately, this efficacy is limited due to its’ cardiotoxicity. This means it can only be administered in small doses and these small doses result in a lower retention rate. Therefore, to get the optimum benefit you would need to increase the dosage, but when you increase the dosage, you increase the risk; a bit of a Catch-22.
Cisplatin was discovered in 1845 but it was not and licensed for medical use until 1978/1979. Cisplatin is used to treat a number of cancers, including testicular, ovarian, cancer, bladder, head and neck, cervical, lung, mesothelioma, esophageal, brain tumors, and neuroblastoma.
Common side effects include bone marrow suppression, hearing problems, kidney problems, (my sister, if she was alive today could attest to this one; her kidneys began failing after several years on this drug) and vomiting (all cancer patients can attest to this one). Other serious side effects include numbness, (this one I can attest to. I have chronic neuropathy in my feet and finger tips. The result is that it is very painful for me to walk unless I have soft-soled shoes on all the time, indoors and out. The numbness in my finger-tips affects my fine motor skills). Trouble walking, allergic reactions, electrolyte problems, and heart disease are other known side effects. Used during pregnancy, it is known to harm the baby.
Fortunately for me, living in Canada, most drugs are covered by our health system, most, but not all. At one point during treatment, my oncologist wanted to give me Neupogen, a drug used to treat the side effects of chemotherapy that staves off deadly infections. The estimated cost for my protocol was $9000. Luckily my wife had a drug benefit plan at her work that covered some of the cost. The remainder was covered by the Trillium Foundation, a Canadian charity for cancer patients. If the coverage was not there from these outside sources, I would not have had access to this therapy.
In the US, the situation is quite different. Most if not all therapy is the responsibility of the patient. The costs for chemotherapy can vary, with some estimates as high as $30,000 over an eight-week period. The average cost for an initial treatment is approximate $7,000. Expenses differ depending on the drugs, the stage of cancer and other factors specific to each patient.
Now, this is what I find most interesting or disturbing about all this. I was given four drugs that have been around for 70, 59, 43, and 39 years respectively. In the case of Doxorubicin, it was founded over 67 years ago but was not licensed for another two decades. Cisplatin was discovered over 172 years ago but was not licensed for medical use for another 133 years.
It is my opinion I was given drugs that are antiquated and have no more efficacy now than they did when they were first discovered. This has led me to the conclusion that my still being alive is based solely on luck. I was one of the lucky ones, the fortunate ones, but how many weren’t as fortunate? And how much money has been raised in the past 40 years for cancer research only to result in us still using the same old drugs? Again, don’t you think it is time to start asking questions?
(Note: The newest bladder cancer drug Tecentriq (atezolizumab) in over 3 decades was approved by the FDA in May 2016. Its success rate is obviously not available. (http://www.webmd.com/cancer/bladder-cancer/news/20160519/fda-approves-new-drug-to-treat-bladder-cancer)
Andrew Glen holds a B.A. in English and Political Science from Western University (UWO). He is married with two sons and lives in London Ont. He is the author of Beating the Odds; a chronicle of his battle with and overcoming Stage IV bladder cancer. War Dads, a fictional novel dealing with the unfortunate events surrounding PTSD and The Grotto and Other Stories a collection of short stories.