This is part 1 of a 3-part series. Part 2 is here. Part 3 is here.
In late June, Peter Guerrieri received a delivery at his row home in Marcus Hook, a small town 30 minutes outside of Philadelphia. The package had come right on time.
Sixty minutes later, an oncology nurse showed up wearing a mask, gown, and gloves . She opened the package. Inside was a carefully wrapped bag of the chemotherapy regimen EPOCH: etoposide, doxorubicin, and vincristine with prednisone and cyclophosphamide.
Instead of a 5-day stay at the hospital for his infusion, Guerrieri, a 62-year-old with aggressive B-cell lymphoma, was about to receive his chemotherapy at home.
"Being in the comfort of my own home and having the freedom to jump in the car to go grocery shopping meant a lot," said Guerrieri, who works as a security coordinator at the QVC television network.
Guerrieri is one of 16 patients to receive EPOCH infusions at home since April 2019 through a pilot program run by Adam Binder, MD, a medical oncologist at the Sidney Kimmel Cancer Center at Jefferson Health in Philadelphia.
Although only a handful of chemotherapy-at-home programs exist in the United States, infusing cancer drugs in the home is not a new idea. Programs outside the United States have provided more than a dozen cancer agents in the home for years, some for decades.
This practice still lies at the margins of oncology care in the United States, in large part due to concerns surrounding safety. In April 2020, the Community Oncology Alliance (COA) said it "fundamentally opposes" infusing chemotherapy and immunotherapy in the home, given the unpredictable, sometimes life-threatening adverse reactions that can occur. In July 2020, the American Society of Clinical Oncology (ASCO) voiced similar concerns, citing "insufficient evidence demonstrating feasibility and safety."
But safety is also a priority for Binder. He spent months carefully selecting cancer agents, patients, and protocols before launching the "EPOCH-at-home" pilot. His goal: Just as cancer therapeutics are shifting from a chemotherapy hammer to a targeted approach, the location of delivery can be personalized as well.
Now, during COVID-19, this mission carries more weight.
"A lot of my patients, especially older patients, don't want to come to the infusion center or hospital because of concerns with COVID," said Binder. "Home-based care is really attractive to them."
Moving Infusions to the Home
Guerrieri felt free. Instead of being tethered to an IV pole inside a cold, sterile hospital room, he could cook, run errands, and take walks around his neighborhood, just like any other day.
The infusion pump rested by Guerrieri's hip, encased in a small, black satchel he slung across his shoulder. Over 24 hours, the pump slowly and continuously suctioned the chemotherapy mixture through a small tube connected to an infusion port embedded in his chest.
During each cycle, he still needed to visit Jefferson's infusion center on two occasions — first to get the pump connected and then to have it disconnected. Otherwise, on the other 3 days, an oncology nurse came to his home to check his symptoms and change his infusion bag.
Just as Binder selected a regimen with a low risk for infusion reactions, he chose participants carefully. All patients had to complete their first 5-day cycle as an inpatient in case they developed severe nausea, difficulty breathing, or tumor lysis syndrome, a rare but potentially life-threatening reaction to EPOCH. Patients also needed central line access, reliable transportation to the infusion center, and education on recognizing the signs of a drug reaction or pump malfunction. Binder also had to feel confident that these patients would actually call the emergency numbers provided if a complication arose.
"If anything went wrong, I knew I could call the infusion center 24/7 or a nurse and get a human being on the other end of the line," Guerrieri said. "I never had to call. But I felt completely safe."
Mapping out the details of delivering EPOCH at home took time. In 2018, Binder teamed up with Nathan Handley, MD, a medical oncologist at Jefferson, who had also been contemplating how to move chemotherapy infusions into the home.
In the United States, models for chemotherapy at home are virtually nonexistent, with one exception: 5-fluorouracil (5-FU). According to the National Home Infusion Association, about one third of the 330 home infusion providers in the United States infuse compounded hazardous drugs, including 5-FU.
But, Binder said, the protocols for administering 5-FU at home do not translate to EPOCH. 5-FU does not involve home delivery of medications, daily nurse visits, or bag changes. Patients on 5-FU get hooked up in the infusion center, go home with a 48-hour pump, and then get disconnected at home.
Outside the United States, however, the two oncologists found a long-standing body of research evaluating the safety and feasibility of chemotherapy across Europe, Canada, and Australia.
A 2016 literature review of 54 papers, for instance, reported no differences in the frequency of adverse events between home and hospital chemotherapy. Of the 22 chemotherapy agents delivered in the home, 5-FU was the most common but others, including high-dose ifosfamide, cyclophosphamide, rituximab, and trastuzumab, had been piloted as well.
A more recent study from Denmark looked at infusions of capecitabine and oxaliplatin at home and at the outpatient clinic in patients with colon cancer. Of 146 home infusions, only two patients experienced grade 2 allergic reactions related to the home infusion itself. Neurotoxicity was the most common adverse event — 11 patients at home and seven in the clinic — and easily managed by reducing or discontinuing oxaliplatin.
Immunotherapy at home appears safe as well.
A 2018 pilot study from the University Hospital Southampton, England, found no adverse events in 10 patients with advanced melanoma who received pembrolizumab during their initial infusion in the hospital and their next three at home. The authors also noted that patients preferred receiving infusions at home, citing time off work and the costs of travel, parking, and childcare as challenges to hospital-based care.
These individual institutional experiences are typically limited to small patient populations, but collectively the body of research highlights a trend.
"Administering cancer drugs at home is not just feasible but is an evidence-based practice. It has been tested, it works, it's safe, and it's effective," said Justin Bekelman, MD, director of Penn Center for Cancer Care Innovation at the Perelman School of Medicine in Philadelphia.
In February 2020, Penn Medicine launched its own cancer treatment-at-home pilot. The program started small with 40 patients and eight certified oncology nurses providing two drugs: leuprolide injections for breast and prostate cancer and EPOCH infusions for lymphoma. Penn Medicine's EPOCH protocol differed slightly from Jefferson's in that patients typically had their pumps connected and disconnected at home.
But like Jefferson's program, the Penn Medicine pilot took months of discussions and coordination with oncology nurses, doctors, pharmacists, and Penn's in-house infusion service about which patients and which drugs would be safe to move into the home.
"We very carefully assessed our safety protocols and use the exact same safety protocols as in the clinic or the hospital that we are just transferring [to the] home," Bekelman said. "When our oncology certified nurses are in the home, they have a sensitivity reaction bag, they have an adverse reaction bag; in short, they have the exact same training and the exact same resources they would have in the infusion suite."
The goal of home chemotherapy, Bekelman said, is to improve how patients experience their cancer care. Even a leuprolide injection, which takes a few minutes, may require patients to take an entire day off to travel to the clinic and wait to be seen.
Another motivation to shift care to the home: Penn Medicine's 13 oncology infusion suites were bursting at the seams.
"Our waiting room was almost standing room only on many days," said Lindsey Zinck, MSN, RN, OCN, associate chief administrative officer for operations for Penn Medicine's cancer service line. "We found ourselves treating a lot of patients in the infusion suite and in the hospital who really didn't need to be there."
When the pandemic hit a month later, it added "unprecedented urgency to our work," said Bekelman, who is also professor of radiation oncology at the Hospital of the University of Pennsylvania.
As COVID cases initially surged across Philadelphia in the spring of 2020, Bekelman began receiving call after call from his colleagues asking, "What about my patient?" The pilot quickly grew from 40 patients in March to 450 patients by mid-July. Given the demand, Penn Medicine also expanded the list of drugs to include bortezomib for multiple myeloma, rituximab for lymphoma, and pembrolizumab for lung cancer and head and neck cancer.
Neither the Penn Medicine nor Jefferson program has encountered any serious safety issues — no extravasations, drug spills, or infusion issues. But Handley acknowledges the high bar for home infusions. A single surprise adverse reaction could topple support during these early efforts.
"One bad event, even if the equivalent would have happened in the infusion suite, would be viewed differently," Handley said.
Managing the Unexpected
Angie Huffine, RN, an oncology nurse in Fort Wayne, Indiana, remembers one particularly bad event.
When she initially led her patient over to one of the 24 blue leather chairs for his second infusion of the immunotherapy nivolumab, Huffine had been at ease. The 60-year-old patient's first infusion at the Fort Wayne Medical Oncology & Hematology Center in early September 2020 had gone off without a hitch. With the IV ready to go, the patient leaned back in his chair, settling in for the 60-minute infusion. Huffine walked over to another patient a few chairs away.
Looking up moments later, Huffine saw the man pitched forward. He had pulled the cloth mask off his face. As she rushed to his side, she could see his shoulders lifting ever so slightly with each panicked shallow inhale. A flush had spread across his face.
"I can't breathe," he rasped.
Huffine stopped the IV immediately and gave him a shot of hydrocortisone and Benadryl to counter the reaction. After placing an oxygen mask over his face, she checked his vitals and alerted the doctor in the next room in case she needed backup.
Within minutes, the patient's heart rate and blood pressure had returned to normal and he finished the infusion with no further issues.
Despite 17 years on the job, Huffine felt rattled by the experience.
"The reaction came as a complete surprise," she said. "It was one of the worst that I've seen to this drug."
Infusion reactions to nivolumab are rare, with mild reactions reported in less than 5% of patients (121/2578) and severe grade 3 or 4 reactions reported in only 0.3%.
"But oncology drugs don't announce, 'Oh, this time I'm going to have a reaction,'" said Lakshmi Aggarwal, MD, an oncologist at Fort Wayne Hematology/Oncology and a COA board member. "The reaction doesn't necessarily happen at the first dose. It can happen at the eighth or tenth dose."
In this case, Huffine said the reaction could have been managed in the home as long as the oncology nurse had access to rescue medications. Still, she admitted, she felt much more comfortable handling this incident in an infusion center, with a doctor just a shout away.
At-Home Safeguards
Penn Medicine has safeguards in place in the event that an infusion reaction occurs. The oncology nurses have an emergency kit with the same medications available in the infusion suite. If the patient's symptoms escalate and require emergency services, the oncology nurse can make a rapid 911 call from the home, which Zinck noted is how most infusion suites across the country work.
"Those reactions are actually managed pretty similarly," Zinck said. "One of the key differences in the infusion suite is that you have a whole team of nurses that you can call in to help you should that situation go down, whereas in the home, it's you and the patient and maybe a family member, with the provider giving orders via phone."
Before administering an infusion, Rebecca Martinez, RN, OCN, an oncology nurse at Penn Medicine's home infusion service, runs through a long checklist. She reviews the patient's labs from the day before, assesses their weight and vitals, double-checks the drug and drug dose, and looks over all prescription medications.
"I'm sitting with the patient getting comfortable," Martinez said. "I often line up pill bottles from the medicine cabinet or insulin from the fridge, and if anything is off, I will call the doctor."
But even with these safety protocols in place, chemotherapy at home is not right for everyone. Some patients feel safer receiving care in the traditional setting, may live in a chaotic household with small children, or even enjoy the social aspect of the infusion center. Others, Handley said, prefer to distinguish between home and hospital and don't want to mix the two.
Drug selection is critical as well. Certain anticancer agents are low risk, but there are drugs that clearly should not be given at home, Bekelman said. Platinum derivatives come with a high risk for anaphylactic-like reactions, reported in 10%-27% of patients. About 30% of patients on taxanes also experience infusion reactions, though only 2%-4% have severe reactions when given appropriate premedications such as corticosteroids and antihistamines.
"There is just too much of a chance of reaction, and the reactions can be quite substantive, so we're not even trying," Bekelman said. "That's not the point here. The point is not to substitute. It is to give patients the option of receiving the treatments at home that they can and that are safe."
Adverse reactions don't just come from cancer agents. Huffine described patients with sensitivities to the antinausea medication aprepitant, and even one patient who had an anaphylactic reaction to the antacid Zantac.
The uncertainty surrounding "how or when a patient with cancer will respond to any drug" worries Miriam Atkins, MD, an oncologist in private practice in Augusta, Georgia. "Many of my patients take a list of other drugs to control heart disease, high blood pressure, and diabetes. Some of my patients are amputees. All of this complicates the kinds of interactions they may have, even with the lowest-risk cancer drugs."
Beyond medications, the home environment can raise red flags for patients and providers. Is the house clean? If the drug is shipped to the patient's home, where is it stored and does it require temperature control? Is the neighborhood safe for the nurse to travel to?
When Martinez enters a patient's home, she looks for these types of red flags. She surveys the space for cat hair or dust on surfaces, or throw rugs the patient can trip over, and inspects the chemotherapy and emergency medications to confirm that they have been stored properly.
"If it's a home situation where there's a higher risk of infection, I provide more education about infection prevention, something as simple as handwashing," she said.
Still, Aggarwal does not see the point in reinventing a system that already works. By moving infusions from a sterile, quality-controlled environment, she worries that the oncologist loses an essential element of control and oversight over her patients.
"Given a complicated situation, why throw gasoline on it," Aggarwal said. "Because we've got better and better drugs, there are more drug interactions and more that we have to pay attention to."
Roadblocks to Home Care
Safety is not the only challenge to scaling up chemotherapy-at-home programs in the United States.
Before the pandemic, Erika Rosato, DNP, RN, OCN, nurse director of ambulatory oncology clinical services at Massachusetts General Hospital (MGH), had big plans to pilot anticancer infusions in the home. MGH already provided leuprolide injections and infusions of hydration, zoledronic acid, and iron to manage patients' symptoms.
But as COVID overwhelmed intensive care units at MGH and oncology nurses got deployed to other services, "we decided quickly that we didn't have the nurses to send into the home to give the drugs," Rosato said.
This feasibility tradeoff is not just a concern during COVID. Oncology nurses are a scarce resource. The economics of taking an oncology nurse who can see five to 10 patients a day in the infusion suite to two patients in their home only exacerbates this shortage, according to Barbara McAneny, MD, chief executive officer of New Mexico Oncology Hematology Consultants in Albuquerque and past president of the American Medical Association.
Financial toxicity is one of the biggest challenges to home care. Like MGH, Intermountain Health in Salt Lake City, Utah, was ready to start a home infusion pilot. David Gill, MD, had selected 20 patients with melanoma to receive immunotherapy infusions at home.
But then everything got put on hold. All insurance companies that had agreed to cover these home infusions, save one, suddenly backed out.
The pilot quickly went from 20 patients to one.
"It was incredibly disappointing," said Gill.
Given the complexity of setting up such a program, McAneny worries that home infusions may become a "luxury good for the affluent." Her patients in the Navajo Nation have no cell coverage, no running water, and dirt floors; they would never qualify for home infusions.
But for chemotherapy at home to be more than a concierge service, institutions in the United States have to start somewhere.
"We need to build evidence in the United States, with our payer system and health infrastructure, first picking off the low-hanging fruit and then moving on to the more complex," said Timothy Kubal, MD, MBA, a medical oncologist/hematologist at the Moffitt Cancer Center & Research Institute in Tampa and medical director of the Moffitt Infusion Center.
Kathi Mooney, PhD, RN, who runs Huntsman at Home at the Huntsman Cancer Institute in Salt Lake City, provides hospital-level care to patients with cancer, including hydration, electrolytes, and total parenteral nutrition, but not chemotherapy so far.
"We are beginning to think about how we would do that and how we would make it safe, especially for patients in rural areas," said Mooney, a distinguished professor at the University of Utah College of Nursing in Salt Lake City. But because it's early days, "you need people who have more of the innovator side to them, who understand the precautions that need to be taken, and who have the commitment to study it."
Aggarwal remains skeptical about safety and feasibility but isn't slamming the door shut completely. "I'm not saying never, never, never. I'm simply saying for a subselect or certain conditions, with certain drugs in a particular situation, possibly," she said.
The Penn and Jefferson teams hope to develop a playbook for chemotherapy at home that other institutions can mimic. And ultimately, Handley and Binder see "home chemotherapy happening whether we like it or not."
For patients like Guerrieri, chemotherapy at home can improve their day to day during a stressful, often frightening time.
"There are no half-days when it comes to getting chemo," Handley said. "If you can give that patient back the day, that's what we're trying to do. If you can liberate some of that time and use it in a more fruitful way, then everyone wins."
Peter Guerrieri, a patient at the Sidney Kimmel Cancer Center at Jefferson Health in Philadelphia who was featured in this story, passed away on January 22. Medscape thanks him for sharing his personal experience with our journalists and with Medscape readers for this story.
This article is part of a series on at-home cancer treatments, including coverage of the reimbursement and economic aspects of home cancer care, at-home cancer care in Europe and around the world, and a documentary video series showing cancer treatments given to patients at home.
Victoria Stern, MA, is a science journalist based in Los Angeles, California. Her work has also appeared in Scientific American MIND, Retraction Watch, and General Surgery News.
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