A new approach to administering intensive chemotherapy for relapsed or persistent cancer allows patients to spend their nights at home, not in the hospital.
Stanford researchers have developed a way to significantly intensify chemotherapy for advanced cancers without requiring patients to undergo bone marrow transplantation. The investigators have been able to administer four cycles of high-dose chemotherapy just 28 days apart by giving patients enriched progenitor blood cells--which quickly rebuild the body's blood-forming system--after each round of therapy.
"When you deliver chemotherapy in the standard fashion, you have to wait three to four weeks between cycles before you can treat patients again because of the bone marrow suppression and the low blood cell counts that result," explained Dr. Gwynn Long, assistant professor of medicine at Stanford. "And if you double the dose, you may have to wait twice as long between cycles--so the dose intensity ends up being the same."
"By using progenitor blood cells to speed patients' recovery between treatments, we can double the dose without waiting twice as long between cycles. This should mean that we can boost dose intensity significantly -- and, hopefully, improve the chance of combating their cancer," Long added.
In their paper, which appeared in the September 1 issue of Cancer, Long and his Stanford colleagues report on 25 patients with either relapsed breast cancer or persistent non-Hodgkin's lymphoma.
"We focused on breast cancer because the outcome of standard bone marrow transplants with metastatic cancer is not as good as people would hope," said Long. "Part of the reason people think it is not so good is because nobody believes that one cycle of high-dose therapy can kill enough tumor cells to get prolonged remissions or cures. And there are a lot of other theoretical reasons to think multiple cycles of dose-intensive therapy should be better."
The First 25 Patients
The first five patients in the Stanford clinical trial were treated in the hospital with chemotherapy and progenitor stem cells. The remaining 20 patients were discharged after the first cycle of chemotherapy, and thereafter, received their cell infusions in the outpatient clinic.
"As this procedure has evolved, it has become an entirely outpatient procedure," said Long. "The chemotherapy can be administered at home by a continuous pump. The patients come into the outpatient treatment facility on a daily basis to be evaluated. If they need fluids or antibiotics, they get those at the hospital. Then, they go home and are usually visited at night by a nurse from Stanford's home-care service. Generally, they visit the hospital daily until their blood counts recover. Then, after a week or so off therapy, they come back to start again.
"Some of the early patients who got this treatment had their first one or two cycles in the hospital and the last two as outpatients,"Long added. They all seemed to like the outpatient approach best."
The most common side effect of the chemotherapy was diarrhea, the researchers reported.
"It is a tough regimen," said Long. "Usually by the end of the fourth cycle the patients are worn out and tired of coming to the hospital, tired of getting chemotherapy and blood transfusions. But some of the common side effects of chemotherapy--like mouth sores and vomiting--were not too severe in these patients."
Several studies with standard-dose chemotherapy have suggested that dose intensity is important to the outcome of chemotherapy, said Long. Recent clinical trials at Stanford and elsewhere have shown that patients who receive progenitor blood cells extracted from the bloodstream recover faster from intensive chemotherapy than do patients who receive progenitor cells from bone marrow. This prompted Long and colleagues to speculate that they could boost dose intensity by using blood, instead of bone marrow, as the source of cells to help rebuild patients' blood-forming system.
Very High Dose Intensity
Researchers at several other institutions are using the same approach, said Long, but the Stanford study used one of the highest dose intensities to date.
While this and other recently published studies demonstrate the feasibility of the new approach, they do not show whether it is better than standard chemotherapy or a single round of chemotherapy combined with bone marrow transplantation, Long noted.
"So, what we are doing now is taking this same approach into a phase II trial, treating women with metastatic breast cancer but being a little more selective about the kinds of patients we are treating," Long said. "They have to have cancer that either is untreated or is responding to standard treatment. In the phase I trial, some patients had been treated three, four, or five times with standard approaches that had little or no effect on their disease. Hopefully, in the new trial, we will get a better sense of whether this is more efficacious than the standard bone marrow transplant approach."
In several prospective, randomized trials evaluating dose intensity, researchers have not seen a significant difference in outcome between the higher and lower dose intensities, said Long. "Most people think the reason is that with no support [such as cell infusions], you really cannot increase the doses sufficiently to make an impact," he said. "With this new approach, you really can significantly increase dose intensity, and we hope we will see a difference."