A new approach to administering intensive chemotherapy for relapsed or persistent cancer allows patients to spend their nights at home, not in the hospital.
A new approach to administering intensive chemotherapy for relapsedor persistent cancer allows patients to spend their nights athome, not in the hospital.
Stanford researchers have developed a way to significantly intensifychemotherapy for advanced cancers without requiring patients toundergo bone marrow transplantation. The investigators have beenable to administer four cycles of high-dose chemotherapy just28 days apart by giving patients enriched progenitor blood cells--whichquickly rebuild the body's blood-forming system--after each roundof therapy.
"When you deliver chemotherapy in the standard fashion, youhave to wait three to four weeks between cycles before you cantreat patients again because of the bone marrow suppression andthe low blood cell counts that result," explained Dr. GwynnLong, assistant professor of medicine at Stanford. "And ifyou double the dose, you may have to wait twice as long betweencycles--so the dose intensity ends up being the same."
"By using progenitor blood cells to speed patients' recoverybetween treatments, we can double the dose without waiting twiceas long between cycles. This should mean that we can boost doseintensity significantly -- and, hopefully, improve the chanceof 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 eitherrelapsed breast cancer or persistent non-Hodgkin's lymphoma.
"We focused on breast cancer because the outcome of standardbone marrow transplants with metastatic cancer is not as goodas people would hope," said Long. "Part of the reasonpeople think it is not so good is because nobody believes thatone cycle of high-dose therapy can kill enough tumor cells toget prolonged remissions or cures. And there are a lot of othertheoretical reasons to think multiple cycles of dose-intensivetherapy should be better."
The First 25 Patients
The first five patients in the Stanford clinical trial were treatedin the hospital with chemotherapy and progenitor stem cells. Theremaining 20 patients were discharged after the first cycle ofchemotherapy, and thereafter, received their cell infusions inthe outpatient clinic.
"As this procedure has evolved, it has become an entirelyoutpatient procedure," said Long. "The chemotherapycan be administered at home by a continuous pump. The patientscome into the outpatient treatment facility on a daily basis tobe evaluated. If they need fluids or antibiotics, they get thoseat the hospital. Then, they go home and are usually visited atnight 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 startagain.
"Some of the early patients who got this treatment had theirfirst one or two cycles in the hospital and the last two as outpatients,"Longadded. 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 bythe end of the fourth cycle the patients are worn out and tiredof coming to the hospital, tired of getting chemotherapy and bloodtransfusions. But some of the common side effects of chemotherapy--likemouth sores and vomiting--were not too severe in these patients."
Several studies with standard-dose chemotherapy have suggestedthat dose intensity is important to the outcome of chemotherapy,said Long. Recent clinical trials at Stanford and elsewhere haveshown that patients who receive progenitor blood cells extractedfrom the bloodstream recover faster from intensive chemotherapythan do patients who receive progenitor cells from bone marrow.This prompted Long and colleagues to speculate that they couldboost dose intensity by using blood, instead of bone marrow, asthe 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 doseintensities to date.
While this and other recently published studies demonstrate thefeasibility of the new approach, they do not show whether it isbetter than standard chemotherapy or a single round of chemotherapycombined with bone marrow transplantation, Long noted.
"So, what we are doing now is taking this same approach intoa phase II trial, treating women with metastatic breast cancerbut being a little more selective about the kinds of patientswe are treating," Long said. "They have to have cancerthat 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 effecton their disease. Hopefully, in the new trial, we will get a bettersense of whether this is more efficacious than the standard bonemarrow transplant approach."
In several prospective, randomized trials evaluating dose intensity,researchers have not seen a significant difference in outcomebetween the higher and lower dose intensities, said Long. "Mostpeople think the reason is that with no support [such as cellinfusions], you really cannot increase the doses sufficientlyto make an impact," he said. "With this new approach,you really can significantly increase dose intensity, and we hopewe will see a difference."