Overview of Cancer Treatment Trials

Overview of Cancer Treatment TrialsKnowing the EnemyIn an era gripped by the promise of cytotoxic chemotherapy, a few dissenting voices was heard. Indiscriminate chemotherapy could not be the only strategy to attack crabmeat. To attack a pubic louse cell, one needed to receive by identifying its unique biological behavior, and vulnerabilities.Hormone Therapy for Prostate CancerCharles Huggins, a urological surgeon at the University of Chicago, was a specialist in diseases of the bladder, kidney, genitals, and prostate. The prostate is a atrophied walnut shaped gland wrapped around the outlet of the urinary tract in men. Cancer of the prostate represents one-third of malignant neoplastic disease incidence in men, six times that of leukemia and lymphoma. In the late 1920s, by performing surgical castration on dogs, Huggins found that the internal secretion testosterone kept both the normal and cancer cells in the prostate alive.Rather than performing a surgical castration on his patients, Huggins injected a female hormone into their bodies to inhibit testosterone function. He called the method chemical substance castration. As with surgical castration, Huggins found that patients responded to the therapy, with minimal side effects. But umpteen of the patients who responded to the therapy eventually relapsed.Beatsons RiddleIn the late 1890s, a Scottish surgeon named George Beatson had learned that the removal of the ovaries from cows changed the quality of their udders and altered their capacity to lactate. Intrigued by the inexplicable link between ovaries and nipples, Beatson surgically removed the ovaries of collar women with breast cancer. To his astonishment, the breast tumors of his three patients shrank dramatically after the surgery. But when surgeons in London tried to apply the method to a larger group of women, only most 2-thirds of the breast cancer patients responded.Solving the RiddleIn the mid-1960s, Elwood Jensen, a young chemist in Chi cago, working with Huggins, came close to solving Beatsons riddle. He found out that estrogen, the principal hormone secreted by the ovaries, worked by binding to a receptor in a target cell. He discovered that breast cancer cases could be divided into two types, depending on whether its estrogen sensitive or insensitive, ER-positive and ER-negative tumors. ER-positive tumors, possessing the receptor, would respond to Beatsons surgery. ER-negative tumors not possessing the receptor, would be unresponsive.The simplest way to prove this theory was to launch an experiment. But the surgical procedure had go out of fashion. An alternative was to use a drug to inhibit estrogen function. But Jensen had no such(prenominal) drug.Tamoxifen TrialTamoxifen was an anti-estrogen compound highly-developed by the hormone biologist Arther Walpole in the early 1960s. In the summer of 1969, Moya Cole, a Manchester oncologist specializing in breast cancer, launched a clinical trial at Christie hospit al in Manchester. Forty-six women with breast cancer were treated with tamoxifen. The response was almost immediate in ten patients. The tumors in the breast and the lung metastases shrank. But like Hugginss prostate cancer patients, many of the patients who responded to the therapy eventually relapsed.Halsteds AshesMoya Coles tamoxifen trial in 1969 was designed to treat women with late stage metastatic breast cancer. But Cole wondered about an alternative strategy. What if women with early stage tumors were treated with tamoxifen?Bonadonnas Adjuvant Chemotherapy TrialA similar idea occurred to a 33-year-old oncologist named Paul Carbone at the NCI ten days ago. Inspired by Min Chiu Li, Carbone had launched a small trial in 1963 and found out that adding chemotherapy after surgery veerd the rate of relapse from breast cancer. Carbone and his team called this handling adjuvant chemotherapy. It would remove microscopic deposits of malignant cells left behind after surgery, completi ng the cancer-cleansing task that the surgery had set out to do.In 1972, an Italian oncologist name Gianni Bonadonna proposed to the NCI a large randomized trial to study adjuvant chemotherapy for early stage breast cancer.In the summer of 1973, Bonadonna began his trial by randomizing nearly four hundred women half to treatment with CMF (a toxic three-drug cocktail) and half to no treatment.Bonadonna presented his results in the winter of 1975. About half of the women in the no treatment group had elapsed era only one-third of the group receiving the adjuvant chemotherapy had relapsed. So adjuvant chemotherapy had prevented cancer relapses in about one in all six patients.The Fisher Adjuvant Tamoxifen TrialWhat if the adjuvant therapy was done with hormonal therapy instead of chemotherapy?In January 1977, Bernie Fisher recruited 1,891 women with early stage ER-positive breast cancer. He treated half with adjuvant tamoxifen and the other half with no tamoxifen. By 1981, he found out that adjuvant therapy with tamoxifen reduced cancer relapse rates by one-half. In 1985, Fisher reported that the effect of tamoxifen treatment was even more dramatic. Among the 500 women older than fifty assign to each group, adjuvant tamoxifen had prevented fifty-five relapses and deaths.Lessons LearnedBy the 1980s, the old paradigms of treatment had evolved into new paradigms. Halsteds radical approach to attack cancer cells was reborn as adjuvant therapy. Ehrlichs magic bullet was reincarnated as hormonal therapy.Although neither of these alternatives offer definitive cures, these trials had confirmed two important principles of cancer biology and cancer therapyThese trials etched the message that cancer was heterogeneous. Cancers came in variety of forms, each with unique biological behaviors. The heterogeneity was genetic well-nigh responded to hormonal treatments, other not. And the heterogeneity was anatomic some cancers were local, while others spread to distant organ s.Understanding that heterogeneity was of deep consequence. It was essential to know the cancer as intimately as possible before hie to treat it. For instance, tamoxifen treatment only applies to ER-positive breast cancers.Palliative CarePalliative care is the branch of medicine that focuses on symptom relief and comfort, founded by Cecily Saunders, an English nurse, physician and social worker. She created a hospice in London in 1967 to care specifically for the terminally ill and dying.Counting CancerIn November 1985, a Harvard biologist named John Cairns measured the progress in the War on Cancer by revitalizing old records that had existed since World War II. He went by dint of the cancer registry, and state-by-state statistics on cancer-related deaths to get a portrait of cancer over time. He used the cancer registry to estimate the number of lives saved by the therapeutic advances since 1950 and divide these therapeutic advances into various categories.His findings were (1)L ess than 5 percent of patients diagnosed with cancer in America and (2) Less than 10% of patients who would die of cancer, had enjoyed the advances in cancer therapy and screening.Cairns psychoanalysis was widely influential, but it needed some measure of the comparative trends in cancer mortality over the years. John Bailar and Elaine Smith from Harvard provided such an analysis in the New England Journal of Medicine in May 1986.Bailar-Smith AnalysisIn the analysis, Bailar-Smith did not use survival-rate analysis because survival-rate analysis can be sensitive to biases such as cancer screenings. They used overall mortality instead. To compare samples over time, they normalized the population to the same standard.According to Bailar-Smith Cancer-related deaths had increased by 8.7 percent from 1962 to 1985. The increase reflected many factors, but mainly because of the increase in lung cancer caused by the increase in smoking rates in the United States. Bailar-Smith noted that th e 35 years of intense efforts to improve the treatment of cancer must be judged a qualified failure.As Cairns had already pointed out, prevention was the only intervention known to reduce the aggregate mortality for a disease. Bailar argued that prevention, as a strategy, had been neglected by the NCI in its pursuit of cures. Treatment strategies received 80 percent of the money while prevention explore received about 20 percent. A similar bias existed in private research institutions. Bailar-Smith noted, A shift in research emphasis, from research on treatment to research on prevention, seems necessary if substantial progress against cancer is to be forthcoming