P&S Journal: Spring 1995, Vol.15, No.2
Increasing the Chance for Success in Cancer Treatment
By Robin Eisner
Ten years ago certain women with late stage breast cancer essentially were given a death sentence by the medical profession. Today these women have a one in five chance of living for five years. The reason for the improvement? High dose chemotherapy followed by what are now routine support treatments-autologous bone marrow transplantation or peripheral blood stem cell therapy.
Under the leadership of Dr. Karen Antman, professor of medicine and CPMC director of medical oncology, physicians hope to further improve the odds. Columbia is one of a handful of academic research institutions aiming to provide the most aggressive research treatment available for breast cancer, Hodgkin's disease, brain tumors, and ovarian cancer. Doctors are planning to give patients anywhere from one to three rounds of high dose chemotherapy followed by peripheral blood stem cell replacement and immunotherapy.
This multiple round therapy is part of the expanded bone marrow transplantation/peripheral blood stem cell replacement (BMT/PBSC) capability developed at Columbia-Presbyterian. Within the past two years, more staff and beds have been dedicated to BMT/PBSC and, as a result, more patients have been treated.
Adult beds for ABMT/PBSC have gone from two to six this year, with another six planned. In 1993, 23 adult patients were treated with BMT/PBSC. By 1994, that number increased to 52. Some 80 patients are expected to be treated in 1995.
Dr. Charles Hesdorffer, assistant professor of clinical medicine, directs the enlarged BMT/PBSC program. Dr. Thomas Garrett, associate clinical professor of medicine, joined the team in July 1994, and Dr. Linda Vahdat, assistant professor of clinical medicine, joined P&S from Memorial Sloan-Kettering in September 1994. The team also has a research nurse and a support staff to help with reimbursement issues for the procedures.
Autologous bone marrow and peripheral blood stem cell therapy are procedures that allow doctors to replenish blood cells, including immune cells important in fighting infection, that do not survive the toxicity of high dose chemotherapy. Bone marrow and blood derived stem cells contain blood-forming precursor cells that regenerate the lost white blood cells, red blood cells, and platelets. Peripheral blood stem cells now are used more often than bone marrow to replace the blood cells.
During traditional ABMT/PBSC, patients first get standard doses of chemotherapy over a six-month period. Then within four to five weeks the patient's bone marrow or stem cells are collected and frozen, high doses of chemotherapy are given, and thawed cells are reinfused. Higher doses may improve survival because they kill more of the metastatic cancer cells present.
"The use of high dose chemotherapy and ABMT/PBSC at CPMC reflects a national trend," says Dr. Antman. In 1989, she says, 274 procedures were reported to the North American Registry of breast cancer patients; in 1992, that number went up to 1,022. Death rates from the procedure have gone down. In 1989, 23 percent of the treatments resulted in death, but the death rate in 1992 was only 6 percent nationally and around 2 percent at Columbia.
In the pending sequential therapy trial, a patient will get three regimens of high dose treatment, followed by stem cell replacement and possibly immunotherapy. Compared to other research facilities doing these kinds of trials, says Dr. Vahdat, CPMC is unique in the drugs being used, the shorter interval of time between use, and the immunotherapy that may follow. CPMC will give taxol first, then melphalan, and finally a cocktail of agents, known by the acronym CTCb, representing the drugs cyclophosphamide, thiotepa, and carboplatin. Immunotherapy, if given, consists of cyclosporin A and gamma-interferon. These two drugs are expected to mobilize the patient's immune system to recognize and kill cancer cells. The trial is open to 25 to 30 people.
Other ABM/PBSC trials are under way or are in planning stages. A gene therapy trial aims to protect patients from the toxic effects of chemotherapy by genetically modifying a patient's bone marrow cells. Another trial will test high dose chemotherapy, stem cell replacement, and immunotherapy for stage II and III breast cancer.
Dr. Antman says recruiting patients for some trials can be difficult. High risk stage II breast cancer patients, for example, know that high dose chemotherapy followed by stem cell replacement appears to improve the response rates for metastatic breast cancer patients and want more intensive treatment too. But in the national randomized clinical trials some stage II patients will not receive the high dose treatment. So, says Dr. Antman, instead of enrolling, many patients will find a doctor who will give them the high dose therapy. "This creates a problem," says Dr. Antman. "Without carefully controlled experiments there is no way to know if the treatment really is improving people's lives.
"It is not enough for an academic medical center to provide the same care that can be obtained elsewhere," says Dr. Antman. "We have a responsibility to improve treatments and advance knowledge. Our trials hopefully will be designed to do that."